ABSTRACTS: 41st Annual Scientific Assembly

ABSTRACTS: 41st Annual Scientific Assembly

ABSTRACTS 41st Annual Scientific Assembi}J American College of Chest Physicians Anaheim, California October 26-30, 1975 Prevention of Tracheal Inj...

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ABSTRACTS

41st Annual Scientific Assembi}J American College of Chest Physicians

Anaheim, California October 26-30, 1975

Prevention of Tracheal Injury in Prolonged Ventilation Through the Use of Self-Inflating Cuffed Ventilating Tubes-Laboratory and Clinical Observations. jacob Abouav; Theodore N . Finley We report our laboratory observations with the use of a self-inflating cuff (sincuf) and our clinical experience in patients. The patient experience included the use of endotracheal, nasotracheal and tracheostomy sincuf mounted tubes. The sealing pressure of the sincuf mounted tube is determined by the intratracheal pressure and therefore never exceeds it. In dogs, the sincuf mounted tube was able to maintain its seal at all pressures and volumes. No significant tracheal mucosal damage was demonstrated even up to six weeks. The sincuf mounted tube maintained a pressure of a column of water 7 em high. No barium was noted on x-ray films distal to the cuff in the lungs of the supine dogs. In humans, no difficulty was experienced in inserting the tube. In all patients, the sealing pressures and ventilation were maintained without any difficulty. There was no episode of clinically ascertained aspirations. No mucosal damage was noted postmortem in patients ventilated for three weeks prior to their ultimate demise. Quantitative Aspects of Cigarette Smoking. William H . Anderson While much valuable information has been obtained by quantifying cigarette smoking by pack-years, it is possible to further describe in quantitative terms various aspects of cigarette smoking. This has been done in 905 individuals by means of puff profile and butt analysis. Puff profile is done by attaching the cigarette to a small pneumotachograph and measuring puff duration, puff volume, number of puffs per cigarette, and total smoking time. From butt analysis, the tar and nicotine consumption per day, year or the smoking lifetime of the subject can be calculated. It is apparent that among one-pack-per-day smokers, tar consumption may vary from 218 to 438 mg and nicotine consumption from 14 to 30 mg, thus this further degree of quantification of cigarette smoking is possible for each pack-year. In ten subjects, puff profile and butt analysis was done on ten separate occasions; each individual had a rather marked consistency in performance, and pattern as measured by these parameters. .\ group of patiems with carcinoma of the lung were found to have a longer duration of puff, a lesser puff volume, and a much longer smoking time per cigarette than the mean for the group of 905. In addition, the lung cancer group also had a greater tar consumption per pack and a more than two-fold calculated increase in tar consumption during their smoking lifetime. Thus, the use of the puff profile and butt analysis technique also has the possibility of selecting those individuals with an increased risk for lung cancer from a smoking population.

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Morphologic and Flow Factors Affecting Patency of Coronary Artery Bypass Grafts. William IV. Angell; ]ef· fery L.Millman; Robert A. Quint; David A. Clark Five hundred seventy coronary artery bypass grafts from 1,774 consecutive coronary artery bypass grafts have had postoperative angiographic analysis. Overall patency of the grafts is 83.9 percent. The patency varied from 86.6 percent from the marginal circumflex grafts to 76 percent for diagonal LAD grafts. Of 33 specimens obtained either at reoperation or autopsy. 12 were from representative intervals of 3 to 32 months postsurgery. Grafts show intimal proliferation and medial fibrosis similar to that seen in experimental canine coronary grafts. While animal studies show a predilection for fat deposit in the grafts, in only two human specimens were atheromatous changes seen and in neither case were these lesions obstructive. Of the 570 grafts restudied. over 230 had electromagnetic flows at surgery. Peak flows and patencies correlate as follows: 0-40 ml fmin, 58 percent patent; 41-80 ml j min. 86 percent patent; greater than 80 ml j min, 95 percellt patency. Reactivity of peripheral bed as tested by 0.6 mg of papaverine also correlate with postoperative patency. Flow data, Silastic castings of anastomosis and comparison of pre- and postoperative angiograms suggest that graft patency depends on anastomotic competence and the distal coronary bed rather than the morphologic changes secondary to arterialization and transplantation. Inftuence of Intrathoracic Pressure Variations on the Increases in Pulmonary Vascular Pressures during Exercise in COPD. Robert C. Bahler; Michael ]. Belman: Edward H. Chester ; Gerald L. Baum We have examined the role of respiratory variation in intrathoracic pressure on the abnormal increase in the pulmonary artery pressure during exercise in 28 participants in a pulmonary rehabilitation study. Extensive pulmonary function studies were performed within se\·eral days of the right heart catheterization. ;\lean pulmonary artery (PA) and pulmonary artery wedge (P.\ W) pressures were recorded at rest and after three minutes of supine exercise. The electrical mean of each pressure was averaged over three respiratory cycles. Respiratory variation in the pulmonary wedge pressure (~PAW) was measured from the phasic pressure recording. Cardiac output was determined by the indicator dilution technique. Resting PA was ;::=: 20 mm Hg in 16 patients while all subjects (N 28) had an abnormal exercise increase in PA (33 ± 8 mm Hg) . The increased ventilation during exercise (VO~ rose from 215 ml j min to 511 ml j min) resulted in an increased ~ PAW from II ± 7 to 19 ± 9 mm Hg. Resting PA\V exc:eeded 12 mm Hg in two subjects and 15 had an exercise PAW ;::=: 15 mm Hg. The exercise PAW showed a positive correlation with exercise

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P.-\W (P <0.01) . Exercise PA was directly related to PAW (P <0.05). Although pulmonary vascular resistance increased slightly during exercise in 17 f28 subjects, it bore no relationship to ~ PAW and was inversely related to exercise Po~ (P
Noninvasive Quantitation of Aortic Stenosis by Doppler Arterial Velocity Waveform Analysis. Robert W . Barnes; Edward A . Rittenhouse; Edwin V. Miller To find a noninvasive hemodynamic correlate of severity of aortic valvular stenosis, axillary artery velocity was assessed by continuous-wa\·e directional Doppler ultrasound. Analogue velocity tracings were obtained in 25 patients with aortic stenosis documented by cardiac catheterization and in 14 normal individuals without cardiovascular disease. From the velocity waveform a ratecorrected velocity upstroke time (VUT) was calculated. This was compared by linear regression analysis with the aortic value area (mean 0.50 cm2jM2, range 0.19 to 0.90 em~ f 1\12) and the mean aortic pressure gradient (mean 54 mm Hg, range 15-117 mm Hg) obtained at catheterization. The mean VUT in normal individuals was 0.11 ± 0.02 sec (± I SD) . In patients with aortic stenosis, the mean VUT was 0. 15 ± 0.05 sec which was significantly longer than normal (P<0.005). The correlation coefficient of the VUT and the aortic valve area was 0.62 (P<0.005) , with a regression equation of (valve area) 0.95 - 2. 77 (VUT) . The correlation coefficient of the VUT and the mean aortic valve pressure gradient was 0.64 (P<0.005). This study demonstrates good correlation between the VUT and catheterization estimates of the severity of aortic stenosis. Arterial velocity waveform analysis using Doppler ultrasound may be a useful noninvasive technique to assess patients with aortic valve disease.

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Hypoventilation-Obesity Syndrome; Central Origin of a Ventilatory Dysrhythmia. Marcos Barrocas; Sudhansu Chokrouerty; George L. Baurn; Arthur Schwartz; john T . Sharp To investigate the mechanisms underlying the obesityhypoventilation syndrome (OHS), 13 patients were studied. In four with OHS, simultaneous polygraphic recordings of electroencephalogram, electro-oculogram, respiration, electrocardiogram , arterial blood pressure and electromyogram of the intercostal muscles were obtained. These patients showed periods of abnormal slowing of the electroencephalogram accompanied by periods of apnea or ineffective breathing, bradycardia, fall of blood pressure and reduction or absence of electromyographic potentials. Control studies in four normal

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obese men and four obese patients with COPD did not show any of these changes. Polygraphic abnormalities persisted in the two cases studied after weight reduction suggesting a central nervous system disturbance independent of obesity. In a fifth patient with OHS, short stature, small mandible and no evidence of COPD. electroencephalogram and spirogram were obtained before and after nasotracheal intubation. Normal spirometric values obtained through the nasotracheal tube eliminated the possible artifact or peripheral airway obstruction contributed by the tube. The patient manifested a dysrhythmic ventilatory pattern with periods of apnea while awake or asleep and prior to and after intubation. The study was repeated after weight reduction with similar results. It is concluded that the main mechanism for hypoventilation in the OHS is central neurogenic with obesity as a secondary aggravating factor. Spirometry and observation of the ventilatory pattern prior to and after intubation can be used as a simple clinical test to differentiate upper airway obstruction from central ventilatory dysrhythmia leading to hypoventilation in the obese subject.

Should Bronchofiberoscopy Aspirates Be Cultured? ] . G. Bartlett;]. IY. Mayhew;] . M . Alexander; S. G. Gorbach Bronchofiberscope aspirates are cultured bacteriologically with the assumption that direct access to the lower respiratory tract permits a reliable specimen. This premise was tested in four series of experiments. All studies were done with a sterilized Olympus bronchofiberscope passed through a sterilized endotracheal tube. Aspirates were collected through the inner channel following topical anesthesia with 2-3 ml of 2 percent xylocaine. Cultures of aspirates in 17 patients without evidence of infection yielded 80 strains of aerobic and anaerobic bacteria; the majority were normal cohabitants of the oropharynx. Previous studies using transtracheal aspirations in such patients yielded sterile specimens. Methylene blue was sprayed on the oropharynx in six patients prior to instrumentation. The marker was detected by spectrophotometric analysis of the subsequent bronchoscopic aspirate in each instance, indicating aspiration of upper airway secretions. Gas chromatographic analysis of 12 bronchoscopic aspirates revealed a mean xylocaine concentration of 1.3 percent (range 0.05-1.91 percent) . In vitro bactericidal curves with I percent xylocaine and the preservative, 0.025 percent methylparaben, showed complete killing of II of 17 bacterial strains after 15 minutes of contact. X ylocaine without preservative was less toxic, but four of five pneumococcal strains could not be recovered after 30 minutes. It is concluded that the channel aspirates from bronchofiberoscopy are an unreliable culture source due to oropharyngeal contamination and the inhibitory effect of topical anesthetic. Changing Epidemiology of Lung Cancer: Increasing Incidence in Women. john F. Bearnis; Am·urn Stein ; joseph L. Andrews, Jr. A dramatic increase in the incidence of lung cancer in both men and women is occurring world-wide. To detail the changes in the epidemiology of lung cancer relating to the incidence in men and women, we reviewed the

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patterns of diagnosis of 1.145 patients with lung cancer seen at the Lahey Clinic in Boston between 1956 and 1972 (during which time the proportion of all men and women seen was unchanged) . The total number of women with lung cancer increased greatly and has almost doubled during this period. Lung cancer in women is now increasing at a faster rate than in men, so that in women the incidence has increased from 13 percent of all cases, or l j 6.8 woman j man ratio (1956-1959) to 29 percent of all cases, a I 2/ .4 woman j man ratio (1969 to 1972) . To examine the relationship between etiologic factors such as smoking, locale and occupation and the specific tumor pathology, we reviewed in detail the case histories and pathology of 231 women with lung cancer. No significant change was evident in cell type distribution during the study years. The most frequently seen tumors in women were adenocarcinoma (31 percent) , undifferentiated large cell cancer (22 percent) , epidermoid carcinoma (16 percent), and undifferentiated small cell carcinoma (12 percent). We divided patients according to the Kreyberg classification into those with group I or smoking related tumors (ie epidermoid, undifferentiated small and large cell tumors) and those with group 2 or nonsmoking related (ie adenocarcinoma) . Among those women with known smoking histories, the group most responsible for the recent increase in women with lung cancer was comprised of smoking women in whom Kreyberg group I smoking-related tumors developed. Thus, we call attention to a new group at high risk for developing lung cancer, namely smoking women. Effect of Physical Training on Cardiopulmonary Function in Patients with Chronic Obstructive Lung Disease. Michael ]. Belman; Edward H . Chester; Robert C. Bahler; Gerald L. Baum We have examined the effect of physical training in 21 patients with chronic obstructive lung disease (COLD) and the results were compared with eight controls. The subjects underwent detailed pulmonary function and hemodynamic testing before and after four weeks of physical training and at the end of one year. The training consisted of daily treadmill walking at increasing speeds and grades. Following the initial training period , the subjects were followed-up for one year during which time they were encouraged to continue exercising. The maximum work load performance as measured on the treadmill at four weeks increased from 6085 to 29958 foot pounds total (P < 0.01) . Evaluation of pulmonary function tests including spirometry. resting lung volumes and arterial blood gases showed no change. No change was seen in the rest and exercising heart rate, stroke index, cardiac index, pulmonary vascular resistance, mean pulmonary anery pressure and the arteriovenous oxygen difference. At four weeks, an increase in the mean pulmonary wedge pressure at rest from 7.4 to 9. 1 mm Hg (P
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associated with a decrease in the l\IV at four weeks from 29.8 to 26. 1 L fmin (P
The Vectorcardiogram in Subjects with Triple Vessel Coronary Artery Disease. Alberto Benchimol; Charles /.. Harris ; Kenneth B. Desser Frank vectorcardiograms were obtained in 98 patients with angiographically demonstrable triple vessel coronary artery disease (> 50 percent obstruction of the right, left anterior descending and left circumflex coronary arteries). Fourteen patients with this degree of obstructive disease had normal resting 12-lead scalar electrocardiograms. Seven of these 14 patients (50 percent) had VCG diagnostic of myocardial infarction (6 / 7) or myocardial ischem ia (1 / 7) . All such detected infarctions were inferior or posterior in location . Three of 14 others with normal QRS complexes and a bnormal S-T segments or T waves had VCG evidence of myocardial infarction . A subgroup of seven patients with a bnormal QRS complexes not diagnostic of myocardial infarction had VCG evidence of the latter diagnosis in 4 j 7 (57 percent) . Nine of 59 with definite ECG Q waves of myocardial infarction had VCG signs of infarctions at other sites which were not predicted by the ECe. There was a close correlation between vee evidence of ~II and a ngiographic site of left ventricular contraction abnormality, even in the absence of MI Q waves on the Ece. It is concluded that the vee is a more sensitive technique than the ECe for the detection of l\1 I in patients with triple vessel coronary artery disease a nd that the vee should be routinely applied for the noninvasive evaluation of patients with suspect chest pain, particularly when the ECe appea rs normal. The Prognostic Significance of Arterial Blood Gases. Paul A. Bilunos; Gary T . Tiznrd ; Paul M . St evens A clinically useful, readily available prognostic indicator is not available in assessing survival in the patient with acute cardiopulmonary disease, despite the recent advances in respiratory care, mechanical ventilation and intensive care units. This lack of a prognostic indica tor gains further importance in selecting patients with respiratory failure for extracorporeal membrane oxygenation. Therefore, in an attempt to arrive at an easily obtain-

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able indicator, we reviewed the patient records and arterial blood gas data obtained by the pulmonary laboratory and intensive care unit of an 1100 bed general hospital from 1967 to 1974, including both surg1cal and medical patients. To insure that only anatomic shunting and cardiac output influenced systemic oxygenation, the only data evaluated was from patients who received 100 percent oxygen by mechanical ventilation or a tight fitting non-rebreathing mask with a reservoir bag for at least one half hour. The lowest arterial oxygen tension recorded for an individual along with the corresponding Pco 2 and pH was evaluated. Two hundred ninety-five adult patients were selected for retrospective analysis. The patients were divided into groups. Based on these arterial oxygen tensions, the survival rates fell progressively in each group as Po 2 range decreased. The overall Pc02 data and alveolar-arterial oxygen grad ients of the patients were not helpful as indicators of survival. Patients with a Po-! of less than 40 mm Hg had a higher incidence of metabolic acidosis and combined metabolic-respiratory acidosis than the other groups. There was no significant difference in the pH among the remaining groups. The arterial J>o 2 response to positive end-expiratory pressure did not influence the survival rates in the severely hypoxemic patients . .\s a reflection of the degree of anatomic shunting with or without a low cardiac output, patients with a Po 2 of less than 50 mm Hg had no significant change in Po-! as the fraction of inspired oxygen was lowered from 100 percent to 60 percent. These data would suggest that the level of arterial oxygen tension obtained while breathing 100 percent oxygen by mechanical ventilation or a tight fitting nonrebreathing mask with a reservoir bag may serve as a prognostic indicator of patient survival in a variety of acute pulmonary diseases.

Improved Sinus Node Sensing after Atropine. joe Bissett; Neil de Soyza; jam es Kane; Mm-vin Murphy Previous studies have shown that the sinus node may not be reset by premature arterial contractions (P ACs) in late diastole, but is reset by PACs falling in a critical portion of the sinus cycle. The purpose of this study was to measure the effect of atropine on sinus node sensing by determining whether atropine changes the area of the sinus cycle where sinus node reset occurs. Fifteen patients were studied by programmed premature atrial stimulation with measurement of the percentage of the sinus cycle (SC) producing sinus node reset. The sinoatrial conduction time was decreased from 109 ± 29 msec to 62 ± 21 msec; P
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(ICU) with simultaneous resumption of anticholinergic medica tions. In order to modify the usual deterioration in neurologic status seen in these patients, we have added corticosteroids to the preoperative and intraoperative regimen . In 1974, eight patients (18 to 62 yrs) were operated upon. They suffered from l\IG from 3 months to 42 years and all had been on alternate d a y prednisone for at least 2 weeks prior to thymectomy. The procedure was done via median sternotomy. Intravenous prednisone (I gm j 24 hrs) was given on the day of operation . All patients were awake at the completion of thymectomy and within one to four hrs could maintain more than 15 ml j kg respiratory tidal volume with an inspiratory effort of greater than 20 em H 2 0 . Arterial Po 2 on room air via on endotracheal tube was similar to preoperative value. Tracheal extubation was done within four hrs after thymectomy in every case and within two hrs thereafter therapy with oral pyridostigmin was begun. The day after thymectomy was considered a cortisone "OFF" day at which time patients were discharged from the ICU (average stay 18 Ins). All patients were discharged from the hospital within nine days on a drug regimen similar to preoperative schedule. This preliminary experience indicates that supplemental corticosteroid therapy may decrease the incidence of postoperative respiratory failure and shortens the period of ICU and hospital stay. Change in Compliance Before and After Treatment of Pulmonary Edema. Roger C. Bone Determination of the comribution of pulmonary edema to any medical illness is imperative, since treatment of pulmonary edema is usually one of the more successful reversible factors in patients with complicating lung disease. To make this determination often requires invasive procedures. The purpose of this study was to determine prospectively if the measurement of thoracic compliance would aid in the diagnosis and assessment ol treatment of patients with left ventricular failure. Another purpose was to determine if complicating disease would invalidate this determination. Twenty-five pa tients, ten with chronic obstructive lung disease (COLD) and acute respiratory failure , ten with adult respiratory distress syndrome, and five with suspected primary left ventricular failure, were evaluated by sequential pulmonary capillary wedge pressures (PCWP) with a balloon-tipped How-directed pulmonary artery catheter. This determination was compared to sequential effective static and dynamic compliance of the thorax at multiple tidal volumes. Compliance and PCWP were performed before and after treatment with diuretics. The static thoracic compliance was sensitive and directly correlated with the magnitude of the PCWP in patients with COLD and patients with primary left ventricular failure. In addition, the sequential measurement of static thoracic compliance accurately reflected mobilization of pulmonary edema fluid. The determination of both static and dynamic compliance allowed evaluation of the roles of airways and lung parenchyma in the process of pulmonary edema. In patients with ARDS, although compliance measurements were nonspecific in determining the role played by cardiogenic versus noncardiogenic pulmonary edema , this measurement allowed a noninvasive determi· nation of mobilization of edema fluid regardless of the etiology. In ARDS, success was obtained in mobilizing edema fluid with diuretics, even in the presence of a

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normal I'CWP. This success was manifest by a decrease in static thoracic compliance and an increase in arterial and mixed venous oxygen tensions. It was concluded that the measurement of compliance is a reliable and useful mea· surement of pulmonary edema. Special advantages of its determination are its simplicity, speed, and noninvasiveness.

and quantity of ventilation are not controlled. The use of minute ventilation as the a bscissa reduces this variability to an acceptable range. FRC correction further improves the analysis. Physiologic and diagnostic interpretations of 13.3xenon washout can be substantially influenced by neglect of ventilatory behavior during washout studies.

Respiratory Drive and C02 Retention during CPAP. B. B. Brach ; G. P. Dolan; R . G. Konopka; V. D. Minh; Kl'llnt'th M. Moser

Incidence of Transient Bacteremia during Bronchoscopy. Charles B . Brearle)•; Theodore R . McNitt ; William IV. Burgin , Jr .; Kenn eth L. Toppell

Increase in FRC results in a relative inefficiency of inspiratory muscles. During CPAP that is known to be associated with an increased FRC, failure of the respiratory drive to mobilize the inspiratory muscles to cope with this mechanical disadvantage would result in C02 retention and decrease in VE. Using dogs under two levels of thiobarbital anesthesia (20 and 30 mgfkg), respiratory drive was measured in the supine position by re<;ording the intratracheal pressure during five consecutive occluded breaths following the obstruction of the endotracheal tube at spontaneous FRC. Respiratory drive index (RDI) was computed as the ratio of the peak pressure of the fifth over that of the first occluded breaths, and changes in PaCO~. FRC and VE (~PaCO~. .lFRC, and ~VE) induced by CPAP (10 em H20) were measured. The data indicate that : I) depression of the respiratory drive (with the high level of thiobarbital anesthesia) resulted in CO~ retention during CPAP ; 2) failure of the respiratory drive to mobilize the inspiratory muscles to cope with CJ>AP could be predicted by measurement of RDI; 3) in clinical application of CPAP, measurement of RDI might allow the prediction of incidences of C02 retention with this type of inhalation therapy.

Twenty-five patients were evaluated during fiberoptic bronchoscopy (FOB) for evidence of transient bacteremia. Blood cultures were obtained from indwelling venous or arterial catheters prior to FOB, upon comple· tion and 5, I5, and 30 minutes post procedure in all patients. Simultaneous throat swabs and bronchial wash· ings were obtained for culture. Patients were excluded from the study who had been on antibiotics within three days of the study, or who had clinical or bacteriologic evidence of sepsis or bronchopulmonary infection. Eleven pa tients had single positive blood cultures ; the organisms isolated included Staphylococcus t•pidennidis (4), Propionibacterium acnes (5) , Serratia marcescem (I) , and Corynebacterium species (I). Three additional patients had two blood cultures positive for Staphylococcus epidermidis. Throat cultures were unrewarding. Bronchial washings were positive in I9 and negative in 5 patients. In only 2 patients, the organisms obtained by blood culture matched those species obtained by bronchial washings ; both of these organisms were Staphy· lococcus epidermidis. No correlation existed between length of procedure, whether or not brushing and j or biopsy was performed , and positive blood cultures. Sepsis did not occur clinically in any patient post-bronchoscopy. as evidenced by absence of fever or hypotension. This study supports nidence recently published concerning the absence of significant bacteremia during bronchoscopy. There is no evidence to support the use of SBE prophylaxis in patients undergoing FOB, contrary to present recommendations of the American Heart Asso· dation , regarding stiff tube bronchoscopy.

Reproducibility of Xenon Washout Patterns in Nonnal Individuals. B . B. Brach ; A . Wright ; V. Sgroi; W . Ashburn ; Kt'nneth M . Moser \Vashout pauerns of 13:lxenon from the lungs have been used to determine the status of regional ventilation, and of regional V /Q relationships both by serial images and by computer generated digital indices. To date, these interpretations of washout have been related only to time, without regard for ventilation dynamics during the washout. In six normal volunteers, we performed ta3xenon ventilation scintiphotography in duplicate with determination of washout slopes and T-1 j 2 calculations in order to detennine (I) the reproducibility of washout patterns and (2) the factors determining these patterns. Variability in duplicate T-1 / 2 values using only a timebased analysis was as great as 38 percent in some lung regions. The average variability of T-1 / 2 for the whole lung washout was 15 percent. When T-I f2 was corrected by using expired ventilation instead of time as the abscissa , variability was reduced so that T-1 / 2 variability for any region did not exceed I8 percent; for the whole lung, 7.5 percent. Further correction for percent normal FRC (helium) of each individual grouped individual T-1 f2's more closely. but did not reduce variability. Great variability in the time-based analysis of 133xenon washout can occur in the same individual if the pattern

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.Metastatic Tumors to Lung. Robert K. Brown ; David Perez-Loria The purpose of this study was to update and widen the indications for resection of metastatic malignant lesions to the lung. Fifty-three consecutive patients with such lesions were rniewed, 4. I percent of 1,29I patients seen for malignant disease in a teaching hospital in a 4 y2 year period. Primary sites were mainly digestive and genitourinary tracts. In 50 lesions, rates of growth were calculated as tumor doubling time, from serial radiographs. There is a close correlation between tllmor dou· bling time and clinical course and outcome. Resecti:m of lung metastases was done in I 4 ope rative procedures in nine patients (7 lobectomies, I segmental. and 6 wedge resections) . Seven of the 9 patients survived up to 4 years 8 months, 6 without any evidence of residual malignant disease. Indications for surgical resection of metastases are outlined. A tumor doubling time longer than 40 days adds an excellent criterion for selection of cases for resection.

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Prediction of Sputum Smear Conversion by Quantitation of Mycobacteria in Initial Sputum Specimens. Martin W. Brueggemann ; C. A. Moore; Robert G. Loudon

Effect of an Interdisciplinary Team on the Health Care of Urban Patients with Lung Diseases. Sharon Bunyan; IJ'hitney Addington

Sputum conversion has classically been used as the best estimate of infectiousness in tuberculosis and time to conversion as the best measure of efficacy of a drug regimen . Sputum conversion occurs when the numbers of organisms in a patient's sputum fall below the number necessary for their recognition, which has been estimated at 9,500 organisms per ml for conversion of the sputum smear. Eady discharge of tuberculosis patients from hospital and the rapid decline in mycobacterial populations with modern antituberculosis drug regimens have led to renewed interest in bacterial quantitation as a means of assessing infectiousness and of gauging response to treatment. Bacterial enumeration using the method of Hobby has been applied to sputum smears three or four times weekly during the first two weeks of treatment of 31 patients with newly diagnosed pulmonary tuberculosis. The results showed rapid decline in the numbers of organisms immediately after the institution of treatment. The relationships between initial bacterial count, rate of decline in bacterial count, and time to conversion have been studied, and the results arc the subject of this presentation. Those who start with higher initial counts (>5.47 X 10" organisms j ml) have a significantly more rapid rate of decline during the first two weeks than those with a lower initial count (<5.47 X 1041 organisms f ml). The relationship between initial count and rate of decline was studied , and used to calculate individual ex· pected rates of decline for each of 31 patients. From this it was possible to estimate time to conversion. These estimates are compared with observed conversion times.

Pulmonary departments in urban, public, training institutions function primarily as consultants to other services. This leads to fragmented long-term care and is undesirable in terms of quality of care as well as patient satisfaction. Inadequacies occur because many pulmonary diseases (chronic obstructive lung disease, asthma, tuberculosis) are diseases that traditionally are uninteresting after the initial diagnosis to medical students, housestaff and attending physicians. However, the successful management of these conditions depends upon comprehensive follow-up and consistent medical management. To attempt to correct these deficiencies in the care of pulmonary patients, an interdisciplinary team of health workers was assembled that consisted of medical corps· men, clerks, practical nurses, social workers, nurses, nurse practitioners, physicians and administrators. The first effort has been with tuberculosis patients. For the first 15 months, 425 patients with active tuber· culosis were seen and initiated on therapy. Of the 269 patients followed in our clinic, 209 (78 percent) were initial treatment and 60 (20 percent) retreatment "failures" from the previous sanitarium based system. Entirely satisfactory treatment courses were observed in 89 percent of patients in an out-patient, team based, less expensive program that includes a brief inpatient (12 day) stay in a general hospital and field visits. Similar success was found in both initial and retreatment patients. These results demonstrate marked improvement over the previous sanitarium-based program in which failure to complete an adequate course of chemotherapy was attributed to alcoholism, antisocial behavior, mental illness and substandard housing. The effect of the team on the patient, nonphysician and physician health provider may serve as a model for the care of urban patients with other chronic lung dis· eases that require prolonged treatment.

In Jlivo and In Jlitro Cellular Immunity following BCG Vaccination. F. Grant Buckle; Henry F. Pabst This study assessed cellular immunity by both in vivo and in l!ltro techniques in tuberculin negative nursing aides who received BCG vaccination. The subjects were in 2 groups : group I consisted of nurses studied in 1974, with mean age 23.2 years (n II) ; group 2 consisted of nurses studied in 1975, with mean age 25.8 years (n 12). .\11 were tuberculin-negative and were given BCG as protection against tuberculosis. Freeze-dried Connaught BCG was used, and all had a "take" at 4 weeks. Skin testing with PPD (5 TU) was done at baseline, and 4, 8, and 12 weeks following BCG. Venous blood was drawn at the above times, and lymphocyte transformation (LTT) by the incorporation of 3H-thymidine was measured. Migration inhibition factor (MIF) was also measured in group I. The PPD became strongly positive by 4 weeks ·(22 mm) and decreased slightly by 12 weeks (15.6 mm). Some subjects showed a strongly reactive L TT as expressed by a mean stimulation index of 26 at 4 weeks. Peak activity was at 12 weeks in group I and at 4 weeks in group 2. Inhibition of migration was progressive from 4 to 12 weeks (0.73-0.62-0.46) and showed a definite in· crease in cell sensitivity to tuberculin. No correlation could be shown between PPD, L TT, and MIF at any time interval. In conclusion , the PPD alone is an inadequate indicator of tuberculin sensitivity following BCG \oaccination. The MIF is the most reliable indicator of tuberculin sensitivity following BCG vaccination.

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Parasternal Mediastinal Approach for Permanent Cardiac Pacemaker Implantation. james IJ'. Calvin; IJ'illiam F. Zuber; Michael Bilitch; Robert A . Steedman; Edward A. Stemmer; john E. Connolly Complications of transvenous endocardial catheter pacing. such as catheter dislodgemellt and ventricular perforation, have led us to prefer direct myocardial elec· trode implantation whenever possible. This is a report of our experience over a ten-year period with a transmediastinal approach to the right ventricle for direct implantation of myocardial electrodes in 66 consecutive patients with a mean age of 74.5 years. The procedure is carried out through a 3-in<:h precordial incision with excision of a single costal cartilage to expose the right ventricle. A retrosternal approach is used to direct the leads to an abdominal generator pocket. There was one hospital death due to unremitting conges· tive failure, but there were no deaths because of the procedure. Only one immediate or late lead complication was observed during a mean follow-up of five years. Advantages of this technique over the transvenous approach are the greater stability of the electrodes and the lower stimulation threshold, thus providing longer

41ST ANNUAL SCIENTIFIC ASSEMBLY 405

battery life. The parasternal approach likewise carried a lower morbidity and mortality rate than the transthoracic approach. It has been our experience that the transmediastinal approach also provides better direct access to the ventricle than does the subxiphoid approach, thus providing increased electrode stability. Tite transmediastinal approach also allows more adequate mapping of the ,·entricular surface to determine the site of lowest threshold of stimulation for longer battery life. The transmediastinal approach can also be employed to provide direct access to the right atrium for direct atrial pacing. Reflex Hyperventilation in Acute Myocardial Infarction. Florencio R. Chavez Acute myocardial infarction was induced in 17 closedchest mongrel dogs by catheterization of selected coro· nary artery and embolized with lycopodium spores. The dogs were anesthetized with morphine and with a combination of pentobarbitol sodium (Nembutal) -dial urethane to hypnotic level. Hemodynamic studies were performed consisting of monitoring of systemic blood pressure, pulmonary artery pressure, left atrial pressure. cardiac output, pulmonary capillary blood volume and total peripheral resistance. The pressures were recorded through the Grass polygraph. cardiac output determined by dye dilution technique and the pulmonary capillary blood volume was gauged by the breath by breath diffusing capacity using carbon monoxide. The heart rate was monitored with electrocardiographic recording. Arterial blood gases, pH and lactic acid were measured using the Instrumentation Laboratory pH/blood gas analyzer 113. A pneumograph recording was made. Pre-embolization studies were made once the dog reached the hypnotic anesthetic level. Hemodynamics and other parameters were monitored from the time of embolization until death of the animal. The result showed immediate increase in respiratory activity, normal arterial oxygen to hyperoxia. severe arterial hypocapnea and acute respira· tory alkalosis. This phenomenon was blocked completely by bilateral vagotomy and partially prevented by pretreatment with beta-blocker. The mechanism of the reflex hyperventilation will be discussed. Coarctation of the Aorta in Children and Adolescents: Surgical Treatment and Review of 120 Patients. Luigi Chiaril'llo; julio Agosti; S. Subramanian Between September, 1967 and April, 1975, 120 patients underwent surgery for coarctation of the thoracic aorta. Eighty-two were males and 38 females. Ages ranged from one day to 20 years. Thirty-two were below two years of age (group I) and 88 above two years (group 2). All patients in group I presented with congestive heart failure (CHF), growth retardation, and electrocardiographic abnormalities indicating left or biventricular hypertrophy. Twenty-eight had associated cardiac defects and 18 had severe pulmonary hypertension (>50 mm Hg) . In group 2, 12 patients presented associated cardiac defects. two CHF, six recurrence of the coarctation. In all but one case, resection of the coarctation and end-to-end anastomosis was performed. In one patient, a Dacron tube graft was used for aortic replacement. Resection of aortic coarctation with end-to-end anastomosis can be safely and successfully performed as an elective procedure. However, it still presents a high surgical risk in infants with associated intracardiac defects.

406 41ST ANNUAL SCIENTIFIC ASSEMBLY

Controlled Comparison of Carbuterol, a New BetaAdrenergic Bronchodilator with Ephedrine and Isoproterenol. Sanford Chodosh; Walter Baigelman; Subbiah Doraiswami Carbuterol (SK&F 40383) , a new beta-adrenergic agent, was evaluated for its bronchodilation elfect in a double· blind crossover study which compared the oral administration of 2. 3, and 4 mg of carbuterol with 25 mg of ephedrine sulfate and placebo, and the nebulized inhala· tion of 200 AA and 400 .ug of carbuterol with 150 .ug of isoproterenol and placebo in patients with chronic airway obstruction with a reversible component. Pulmonary function, pulse and blood pressure were measured at 0, 30, 60, 120, 180. 240, and 300 minutes for the oral route in 10 patients and at 0, 5, 15, 30, liO, 120, 180, 240, 300, and 360 minutes for the nebulized route in 10 patients. :\ll three doses of oral carbuterol had consistent improvement when compared with placebo for the one second forced expiratory volume (FEV 1) and the maximal mid· expiratory flow rate (l\l.i\1 EFR) starting one 10 two hours after administration and lasting until five hours. Ephedrine sulfate resulted in significant bronchodilation as compared with placebo only at the 2-hour observation for the l\11\1 EFR. Heart rate and systolic blood pressure increased sigoificantly at several observation times after administration of carbuterol, the higher doses having the greatest incidence. The cardiovascular indices after nebulized administration showed few significant changes with isoproterenol or carbuterol when compared to placebo and those that occurred were in a beneficial direction. Carbuterol and isoproterenol manifested significant improvements for the forced vital capacity, FEV I· and l\IMEFR for experimental points less than one hour after inhalation . Both the 200 .ug and 400 .ug doses of carbuterol showed significant improvement for the FEV1 and Ml\IEFR when compared with isoproterenol at points later than one hour. Carbuterol appears to be an effective bronchodilator when used via the oral or nebulized route with significantly prolonged anion as compared to ephedrine and isoproterenol respecti\·ely. Survival Factors in a Respiratory Unit. E. Leslir Chusid; C. Baserico; j . Tricarico; C. Sinha; 1·: . Prmgan; john Dwek The management of acute pulmonary failure has been vastly improved through the experience gained in respiratory care units. To further evaluate those fanors con· tributing to survival in patients with acute pulmonary failure, data from 1,093 consecutive patients, admitted to a 12-bed respiratory care unit over a three-year period. were analyzed. The diagnoses encompassed any disease or clinical state leading to pulmonary failure, and the ranges of arterial blood gas analysis were pH 6.85-7. 75, Po~ 14-468 torr, and J>co-~ 10-161 torr. Constant surveillance was maintained by RCU personnel and appropriate moni· toring devices. The number of deaths was 142 (13 percent mortality). with the mortality in patients with COPD being 10.1 percent (36/356) . Hypercapnia was not a significant factor, since with appropriate therapy only 7 j72 patients with Pco~ greater than 80 torr succumbed (9. 7 percent mortality). The least survival was in those patients with severe hypoxemia, ie , Po-2 below 30 torr (36.4 percent mortality) and in those patients with combined

CHEST, 68: 3, SEPTEMBER, 1975

metabolic acidosis, pH <7.2, and hypoxemia of any degree (21 .4 percent mortality) . Infection, with use of present day antibiotics, played little role in mortality. only three deaths being attributed to sepsis. However, secondary organ failure accompanying the pulmonary failure (cardiac, renal, hepatic) did affect survival dramatically (63 /142 deaths, 44.5 percent mortality) . Survival in patients with overdose and in all types of pulmonary edema (210 patients) was better than 95 percent, demonstrating the importance of early intubation and rapid correction of arterial gas and metabolic derangements as carried on in an organized respiratory unit. Thus, survival in acute pulmonary failure seems to be influenced by I) the type of pulmonary failure, 2) the presence of failure of other organ systems accompanying pulmonary failure, and 3) the necessary adjustments required to correct severe hypoxemia and metabolic acidosis. Detection of Acute Perioperative Myocardial Damage by D9"'Tc Pyrophosphate Scanning. R. C. Curry, Jr.; Allen K. Tonkin; Marc H. Freeman; Peter V. Moulder; Carl ]. Pepine; C. Richard Conti Patients undergoing open heart surgery (OHS) frequently exhibit postoperative elevation of serum enzymes and ECG changes mimicking acute myocardial infarction. Exclusion of perioperative myocardial damage may be particularly important when reoperation and other patient management decisions are contemplated. We therefore performed serial, multiple projection, preand postoperative 1lD"'Tc pyrophosphate scans (PYP-S) in a group of OHS patients to determine its usefulness in detecting perioperative myocardial damage. Myocardial damage (increased regional cardiac uptake of PYP over background) was found in 7 of 30 patients studied up to 7 days postoperatively. In 2 patients, a positive scan was associated with new Q waves and serum enzyme elevation. Three patients with positive postoperative scans showed no diagnostic ECG or enzyme changes, but had occluded grafts and ventriculographic findings at repeat catheterization in the same distribution of the positive scan. The two other patients who did not survive surgery showed acute myocardial necrosis at autopsy confirming the positive preoperative scan. In patients with negative preoperative scans who either did not survive (9) or were recathed (2) , there was no evidence of acute myocardial damage. llii"'Tc PYP-S appears to offer a specific and sensitive new method to detect acute myocardial damage during the high risk perioperative OHS period. A Comparative Evaluation of Impaired Antibacterial Defenses of the Lung by Products Commonly Smoked by Man. M. Cutting; Gary Huber; G. Simmons; W . Pereira ; Raul Laguarda Considerable controversy continues to surround the issue of smoking and health. Potential health hazards associated with cigar, synthetic tobacco substitute and marihuana smoke consumption have not been extensively evaluated. To study this, comparative effects of smoke from Kentucky reference tobacco, reference cigars, Cytrel synthetic smoking material and marihuana on alveolar macrophage (AM) bactericidal activity were evaluated.

CHEST, 68: 3, SEPTEMBER, 1975

Rat AM were harvested by pulmonary lavage and in vitro bactericidal inactivation of S albus quantified. Control AM inactivated 74.8 ± 1.8 percent of bacteria after 3 hours of incubation. Exposure to 8 ml of fresh smoke from each product impaired bactericidal activity to 16.7 ± 0.7 percent, 21.9 ± 2.5 percent, 13.7 ± 1.5 percent and 11.4 ± 7.6 percent for cigarette, cigar, tobacco substitute and marihuana smoke, respectively . .-\dministration of graded amounts of each agent demonstrated that this depression was dose-dependent for all products. Absolute and differential filtration of all smoke products revealed that the cytotoxin was in the gas phase of the smoke, was highly water soluble, and was inactivated in stale smoke. These results indicate that a water soluble component of fresh smoke from all commonly consumed smoking materials is equivalently cytotoxic to the AM in a dosedependent manner, significantly impairing the bactericidal activity of the key host defense cell of the lung under these experimental conditions. By all criteria studied, there was no discernible difference in the effect of each smoking product, implying that potential health hazards to man from cigar, tobacco, synthetic tobacco and marihuana all deserve further clarification. Diffuse Idiopathic Interstitial Pulmonary Fibrosis Associated with a Qualitative Platelet Dysfunction: A New Syndrome. Brian H. Davies A syndrome of severe oculocutaneous albinism and platelet "storage pool disease" was associated with the physiologic and radiologic features of idiopathic interstitial pulmonary fibrosis in several siblings of a first cousin marriage. Two siblings, one of whom succumbed to her disease, showed progressive respiratory impairment. Subsequent investigation of unrelated subjects with oculocutaneous albinism showed no evidence of pulmonary fibrosis or platelet "storage pool disease." However, one unrelated normally pigmented subject with severe platelet "storage pool disease" was found to have physiologic evidence of pulmonary fibrosis, but normal d1est x-ray film findings. Review of the two original cases with platelet "storage pool disease" showed both subjects as having unexplained diffuse pulmonary fibrosis. It is suggested that the diffuse idiopathic interstitial pulmonary fibrosis associated with platelet dysfunction may be a manifestation of a common abnormality in phospholipid metabolism in the alveolar pneumocyte and platelet. Longterm Results of Mitral Valve Replacement with Hancock's Porcine Xenografts in 207 Patients. julio C. Davila : Mehdi Hakimi; £/let H. Drake: Daniel T. Anbe; Donald]. Magi/ligan, Jr. During 4 years, 207 patients have had mitral valve replacement alone (151) or with aortic andfor tricuspid replacement. The initial hospital mortality was 2.9 percent among I 04 status 3 patients and 20.3 percent overall. Follow-up (100 percent) reveals that 96.4 percent of 165 patients discharged from the hospital are alive I to 44 months postoperatively, (3,300 patient-months, average 20 ± 7). These patients received 203 xenografts which have functioned with no valve failure for 4,060 valvemonths! Postoperative cardiac catheteriT.ation has been performed in 28 patients. There has been marked reduction in pulmonary hypertension (from 59± 18 to 33 ± 9

41ST ANNUAL SCIENTIFIC ASSEMBLY 407

mm Hg), and valve gradients (mitral : from 19 ± 8 to 2 ± I; and aortic: from 65 ± 8 to II ± 6 mm Hg). Cardiac output rose (from 2.1 ± I to 3.2 ± I LfminfM2) . Sixteen patients (7. 7 percent) had postoperative emboli. In all but two (87.5 percent) there were two or more non-valve related thrombogenic factors such as atrial fibrillation , massive atrial enlargement, infection, previous thromboembolism, congestive heart failure or low cardiac output. The data indicate that surgery in earlier stages of disease is necessary to reduce risk, decrease thromboembolism and enhance postoperative status of patients, even though salvage of >65 percent far advanced cases is possible. This xenograft preparation has held up well and yielded extremely low rates of complications. Surgical Treatment for Pulmonary Emphysema. Norman C. Delarue; Colin Woolf Interest in the possibility that surgical treatment might be helpful in managing patients with emphysema arose as a result of careful assessment of the gross findings encountered during thoracotomies for other diseases. It became apparent that emphysema is rarely generalized, that the central portions of the lung may be less seriously affected, and that marginal folding with secondary obstruction develops when the lung is too large for the pleural space. Practical clinical classifications must emphasize the unifocal or multifocal nature of the changes and the fact that space-occupation may occur in both instances. The extent of the destruction and its location can be most accurately defined by pulmonary angiography. Excision of destroyed avascular space-occupying areas allows the compressed and more normal lung to be stretched to fit the pleural space in a functionally effective fashion . Residual elastic tissue will now maintain patency of terminal bronchioles. Surgical treatment for unifocal emphysema (with or without space-occupation) produces excellent results. However, the role that surgical treat· ment may play in multifocal emphysema (with or with· out space-occupation) is less clearly defined. In 25 patients of this latter type followed at least one year, more than 50 percent showed improvement in blood gases, diffusion capacity, and tests of the mechanics of breathing, thereby providing objective evidence to substantiate reports of subjective improvement following operation. The indications for surgical intervention in these patients will be summarized. Value and Limitations of Echocardiography as Compared to Cardiac Catheterization in Assessing the Hemodynamic Consequences and Prognosis of Acute Myocardial Infarction. A . DeMaria; }. Angel; Ezra Amsterdam; Dean T . Mason Stroke work index (SWI), obtained by right heart catheterization has been demonstrated to accurately reflect the extent and prognosis of acute myocardial infarction (AMI) . Since echocardiography provides an atraumatic technique by which cardiac function may be assessed, we attempted to utilize echo to construct an index of ventricular performance of quantitative and prognostic value similar to SWI. Echocardiography and right heart cateterization were performed simultaneously in 38 patients within 36 hours (average 12 hours) of

408 41ST ANNUAL SCIENTIFIC ASSEMBLY

AMI. Ten patients suffered pump failure and death following infarction and were classified as nonsurvivors (NS), while 28 patients survived (S) the infarction. SWI, determined by catheterization, was markedly reduced in NS 10.5 as compared with survivors 33.3 (P <.001). No separation could be found between NS and S in echographic stroke volume and cardiac output, although echo end diastolic dimension (EDD) was greater 6.4 to 5.2, ejection fraction (EF) (EdD-EsD f EdD) less 35 to 55 percent and VCF less 0.71 to 0.96 in NS (all P< .OJ) . Subsequently, a noninvasive index was formulated (NI) as NI EF (BP f EdD) where EF and EdD were ob· tained by echo and BP by cuff sphygmomanometer. NI correlated very well with SWI (r 0.83, P< .OOI) and was markedly reduced in NS ( 18. 1) as compared with S (44.6 P< .OOI). Moreover, only I NS had an NI o( above 22 whereas only I S had NI below this value (P < .001) . Thus, echocardiography may be employed to calculate an index of ventricular performance in patients with myocardial infarction which correlates well with that obtained by cardiac catheterization. This noninvasive index provides a sensitive method to assess the prognosis in infarction patients.

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Single Breath Washout Curves in Regional Volumes and Sequential Ventilation in COPD. M . Demedts; M. De Roo; ]. Cosemans; A . Vandecruys, K. P. van de Woestijne In 15 patients with COPD, single breath t:l:!xenon and N 2 washout curves and regional volumes were measured . Four patients with primarily emphysematous loss o( elastic recoil and minimal central airway obstruction presented increased closing volumes with both methods due to an accentuation of the effect of the gravitational pleural pressure gradient. One patient with small airway disease showed an increased closing volume with the l:l:!Xe method, but almost no closing volume with the N~ method due to the fact that basal zones closed at high volumes, although nongravitational uneven ventilation was absent above closing level. Six patients with chronic bronchitis showed with both methods upward sloping alveolar plateaus without distinct phase 4. This indicated an uneven sequential ventilation during the whole expiration which, however. still presented a first-in ( last-out distribution, corresponding to progressive closure, starting in the units with the smaller residual volumes. Four patients with severe COPD and basal emphysema presented a downward !33xe plateau and an upward N~ plateau which could only be explained by a first-in ( firstout distribution, determined by nongravitational differ· ences in time constants. From the slopes of the t:l:!Xe and N 2 plateau, the relationship between sequential ventilation and regional volumes can be analyzed and the mechanical basis for it can be determined. Local Glossopharyngeal and Superior Laryngeal Nerve Block Anesthesia for Peroral Endoscopy. Tom R. De· Meester; David B. Skinner; Richard H . Evans; Donald W. Benson Local glossopharyngeal and superior laryngeal nerve block anesthesia for peroral endoscopy has been performed on 128 patients (98 bronchoscopies, 30 esophagoscopies). The technique involves a bilateral I percent lidocaine (Xylocaine) nerve block of the glossopharyn-

CHEST, 68: 3, SEPTEMBER, 1975

geal nerve at a point y2 em behind the mid portion of the posterior tonsillar pillar. Bilateral superior laryngeal nerves are similarly blocked by an injection of I percent Xylocaine at the cornu of the hyoid bone. The superior laryngeal nerve block is not necessary for esophagoscopy. The technique allows easy insertion of rigid and flexible scopes, or an endotracheal tube through which fiberoptic bronchoscopy can be performed. In all patients, a temporary abolition of the gag reflex was easily and quickly achieved and excellent to good anesthesia was obtained. Two patients experienced a headache and one, nausea, following the block. One patient had a brief episode of tachycardia during the procedure. There was one episode of aspiration and one broken tooth during intubation. Two patients had respiratory arrest during fiberoptic bronchoscopy and were resuscitated without difficulty by assisted ventilation through the endotracheal tube. There was no death. No special precautions have been observed and antibiotics have not been used. The possibilities of inducing infection , intra-arterial injection or hemorrhage secondary to injection into a dangerous area through a contaminated field was a concern , but no such complications have been encountered in our routine utilization of this method. We feel that there is no increase in risk to the patient when this method is employed and would recommend it as an excellent means of obtaining anesthesia for outpatient endoscopy with good patient acceptance.

Gastroesophageal Reflux and Pulmonary Aspiration: Incidence, Functional Abnormality and Results of Surgical Therapy. Tom R . DeMeester, Lawrence F. johnson Seventy-four patients with gastroesophageal reflux measured by 24 hour pH monitoring of the esophagus were prospectively divided into two groups-aspirators and nonaspirators-on the basis of a sudden burning lateral chest pain associated with cough and a vomit taste in the mouth . Each patient underwent esophageal manometry, and an abdominal compression test. The 24 hour pH record and test results were analyzed and the two groups compared. Thirty-four aspirators (46 percent of reflux patients) had a greater amount of reflux during the 24 hour period (P= < .01) due to a greater amount of reflux in the supine position (P= < .05). Both groups had the same amount of reflux in the upright position . The number of reflux episodes in the supine position was the same for each group but the average length of a reflux episode was longer in those who aspirated (P= < .01) . There was no difference between the groups in the cricopharyngeal and DES pressure or the length of the DES. The aspirator had less DES exposed to abdominal pressure (P= <.05) and a higher incidence of + abdominal compression tests (P= < .05) . Sixteen patients with aspiration had an antireflux procedure and were re-evaluated 4 months post surgery. Fifteen were free of aspiration, had a normal 24 hour esophageal pH record, showed a significant increase in both DES pressure and the amount of DES exposed to abdominal pressure, and an improved abdominal compression test. Patients with supine reflux which clears slowly are susceptible to pulmonary aspiration. Antireflux procedures correct the abnormality and stop aspiration.

CHEST, 68: 3, SEPTEMBER, 1975

Correlation of Ventricular Arrhythmia Detected during Holter Monitoring, Treadmill Testing and Isometrics in Convalescent Myocardial Infarction Patients. Neil de Soyza; joe Bissett; james Kane ; Marvin Murphy In order to evaluate the reliability of Holter monitoring (HM) versus stress testing in detecting ventricular arrhythmia (VA) in myocardial infarction (M I) patients prior to hospital disdtarge, 52 patients in their third post MI week had 24 hour HM performed prior to performing isometric handgrip for 30 seconds at 50 percent peak grip. After a 10 second rest period, all patients walked for 3 minutes at 1.5 MPH at zero grade on a treadmill. We concluded that HM is more reliable than modified stress testing in arrhythmia detection in convalescent MI patients, no complications were noted during modified isometric and treadmill stress in these patients and longterm followup studies are needed to determine the prog· nostic significance of these findings. Simultaneous Surgical Correction of Coronary and Peripheral Vascular Arterial Lesions. Edward B. Diethrich; Claudio Zamorano; Ravindranath Koopot Signs and symptoms of arterial insufficiency are usually related to the segmental nature of the atherosclerotic disease process. Occasionally, arterial lesions produce symptoms of both coronary and peripheral vascular insufficiency which are best tested by simultaneous operative correction. This report details our experience in treating (I) carotid artery bifurcation disease: (2) subclavian stenosis with steal syndrome; (3) aneurysm of the abdominal aorta; (4) aortoiliac occlusive disease : and (5) femoral-popliteal occlusive disease in conjunction with aortocoronary artery bypass. The proper sequence of operative procedures, the influence one lesion may have on another and the various technical considerations have been examined in a group of 30 patients. There was no operative mortality, even though combined procedures were performed. Postoperative morbidity may in fact have been reduced since the potential for complication from the peripheral lesion (ie stroke, ruptured aneurysm) has been eliminated. In general, lesions capable of producing cerebrovascular insufficiency are given precedence over other arterial lesions, except in cases of impending disruption of arterial continuity or organ perfusion. The principles of management used in these specific clinical situations and the results will be presented. Pulmonary Reaction to Upper Mantle Radiation Therapy for Hodgkin's Disease. G. A . doPico; A. Wiley ; P. Rao; Helen Dickie A case of fulminating diffuse radiation pneumonitis prompted the study of the effects of upper mantle radiation therapy on pulmonary function . FEV 1 , FVC, IC, RV, TLC, D,.CO and DLJVA were determined in 29 patients with Hodgkin's disease stages 1-3 before therapy and at regular intervals thereafter. A maximum mean group decline in all functions (as a percentage baseline) was apparent between the 80th and !50th day postradiation which returned to pretreatment value (±5 percent) by the 8th to 12th month. D ..CO showed the greatest decline in the largest number of subjects (22 J28) . Maximum mean decline in D,_CO was -12.7 ± 3 percent at the 87th :±: 3 days sustained through the !50th day

41ST ANNUAL SCIENTIFIC ASSEMBLY 409

improving thereafter. The frequency of decline in DLCO was significantly higher (P < .01) among those who also received abdominal periaortic radiation inferring some relationship. The changes seemed to be independent of radiation dose, clinically apparent intra-thoracic Hodgkin's, postradiation, dJest radiographic abnormality and respiratory symptoms. Although the changes in IC and VC were of less magnitude, they correlated well with D~.CO changes. The impairment in gas exchange and loss of lung volumes indicate a diffuse pulmonary reaction despite lung shielding. Although the functional losses are prolonged, they are transient and subclinical in most but not all cases. Follow-up of Tuberculosis Patients Treated Largely as Out-Patients. A. K . Dull ; D. L. Miller; W . P. Reagan; H. Swindo/1; / .. jones; IV. IV. Stead \Ve report the results of 4 to 7y2 years of observations of 353 patients with tuberculosis who were briefly ad· mitted to a general hospital between July, 1967 to the end of 1970 and then treated largely as out-patients. Thirteen patients died during initial hospitalization, 4 of tuberculosis: 340 were released to continue therapy at home, 315 (86.4 percent) within 2 months. One hundred thirty· six (38.5 percent) were discharged before sputum conversion and appeared to cause no secondary cases. Two hundred eighty-six (84 percent) completed 18 months of chemotherapy as out-patients and remained well. Fifty-four did not complete the treatment because of nontuberculous death (25), moving to another state (14). deaths due to tuberculosis (4) and treatment fail· ure in II (3.2 percent) . Thus, the ultimate success rate of 301 patients (340-39), who remained in the state and did not die of other causes was 286f 301 (95 percent). Long-term follow-up of these 297 cases (286 successfully treated and II treatment failures) revealed 6 cases of relapse during the period. Fifty-two patients were lost, 43 (14 .5 percent) due to deaths from other causes and 9 (3 percent) moved to another state while still well. Thus, there were 6 (2.5 percent) relapses among the remaining 245 patients (297-52), and the overall success rate was 97 .5 percent. Of the 17 cases (II treatment failures and 6 relapses), II were successfully retreated with 18 months of chemotherapy. and 3 are continuing on therapy and remain negative : 3 did not complete treatment, as 2 died and I moved to another state. Success of such a program depends upon well organized chest clinics, diligent public health nursing and continual staff education. Total and Pulmonary Blood Volume in Stable and Acutely Decompensated Severe Chronic Airways Obstruction. jameJ H . ElliJ; David C. Levin ; Peter P. Steele Quantitative radiocardiography (QR) using 133mindium provides an accurate means of measuring total blood volume index (TBVI), cardiac index (Cl) and pulmonary blood volume index (PBVI) . QR was ap· plied to 74 patients with severe (FVC 2.75 ± .13 liters; mean ± SEM : FEV 1 0 1.08 ± 0.07 liters) but stable (S) chronic airways obstruction (CAO) and 50 patients with severe (FVC 2.30 ± 0.14 liters, FEVto 0.91 ± 0.10 liters) CAO and acute decompensation (AD) characterized by increased hypoxemia and acute respiratory acidosis. Right

410 41ST ANNUAL SCIENTIFIC ASSEMBLY

heart catheterization was performed in 46 patients with SCAO and in 32 patients with ADCAO. In ADCAO cardiac index (3 .77 ± 0. 16 L j min fl\-12) was increased and significantly (P < .05) inneased compared to SCAO (3.40 ± 0.08 L j min j J\12) . The PBVI in SCAO (335 ± 5 ml / M2) and ADCAO (369 ± I 0 ml f l\12) was significantly increased (P < 0.001) over normals (n 29: 310 ± 4 ml j l\f2). The TBVI in SCAO (3.02 ± .06 L J M:!) and ADCAO (3.46 ± .II L f J\12) was significantly (P < .00 I) increased over normals (2.82 ± 0.04 L f J\12) . The increase in PBVI in ADCAO compared to SCAO may relate to the significantly increased (P < ().()I) pulmonary arteriolar resistance index (PARI: 644 ± 66 dynes cm-5 compared to 488 ± 40 dynes cm-5) and mean pulmonary artery pressure (PAP: 36 ± 3 mm Hg compared to 28 ± 2 mm Hg) as well as the increased TBVI. Data suggest that the PBVI and TBVI arc increased in AD and SCAO although the changes in PBVI are more pronounced in ADCAO probably because of the higher TBVI, PARI and PAP.

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Localization of Bronchogenic Carcinoma in Tuberculous Lobes. David j . Farwell; Lewis j . Rutledge ; Lt~ster R . Bryant; Frednick G. Schechter The pronounced predilection of bronchogenic carcinoma for tuberculous lobes of the lung has not generally been recognized. In this study. tuberculous lesions were confined to one or two lobes of the lung in 24 (77 .7 percent) of 27 patients with coexisting bronchogenic carcinoma and tuberculosis. In 21 (87.5 percent) of the 24 patients with localized tuberculosis, the neoplasm arose specifically in a tuberculous lobe. An analysis of 12 patient series, including this study, reveals an average of 58 percent of patients with coexisting disease with the neoplasm in a tuberculous lobe. Diagnosis in this series required an average of 1.8 months (range: I week-18 months) . Difficulties in diagnosis result from (I) low index of suspicion: (2) unclear cytologic diagnosis in the presence of AFB positive sputum: and (3) the fact that radiologic diagnosis must await tumor or hilar enlargement, or spread of disease. The data suggest that a heavy smoking, tuberculous, male patient over the age of 50 years with a lesion which is enlarging or which is in an unusual location, and who has shown moderate drug resistance should be highly suspect. Sputum cytology. bronchoscopy. and early thoracotomy arc advocated . Can Right Heart Medium Injections Cineangiograms in ease? jack Ferlim.; Richard Gorlin

("Forward") Angiographic Contrast Produce Satisfactory Left Ventricular Patients with Coronary Artery DisMichael V . Haman ; J>l'lt•r F. Cohn ;

Left ventricular (LV) cineangiograms are essential for a complete evaluation of patients with coronary artery disease. Specifically, the adequacy of the LV ejection fraction determined from these studies is frequently used as an index for the selection or rejection of patients for coronary artery bypass surgery. The standard LV cineangiograms are performed hy selective injection of contrast medium directly into the LV chamber. Right heart ("forward .. ) injectiom, however, are also sometimes used in the assessment of LV performance. This technique consists of injecting the contrast medium into the right ventricle or pulmonary

CHEST, 68: 3, SEPTEMBER, 1975

artery, and then filming the LV as the dye passes through in the "levophase." In order to compare this method to the standard (selective) LV cineangiography. 10 patients with coronary artery disease were studied by selective injection of contrast medium into the LV cavity followed by injection into the right ventricle and filming the levophase. Levophase injection was performed at least 60 minutes after the selective injection and at least 30 minutes after coronary arterio1,rraphy, and only if heart rate and pressures remained essentially unchanged. Biplane cineangiograms were used to calculate the end-diastolic volume index (EDVI) , end-systolic volume index (ESVI), stroke volume index (SVI) and ejection fraction (EF) . Values for the two respective techniques were then compared. Not only were correlation coefficients for the two methods low, but there was also a statistically significant difference between the two SVI (P<0.02) and the two EF (P
CHEST, 68: 3, SEPTEMBER, 1975

PA WP) , cardiac output (CO) , pulmonary vascular resistance (PVR) , pHa, PaCO~ and Sa02. Three groups were identified: I) pHa < 7 .35 (mean 7.28 ± 0.01 SEM, 26 patients); 2) pHa 7.35-7.45 (mean 7.40 ± 0.01, 26 patients); and 3) pHa > 7.45 (mean 7.52 ± 0.01, 23 patients). None of the hemodynamic parameters was significantly different in the three groups. When patients with marked acidemia (pHa ~ 7.25, mean 7.15 ± 0.02, 7 patients) were compared to those with marked alkalemia (pHa ~ 7.55, mean 7.57 ± 0.01, 10 patients) only PVR was significantly different. When the 27 patients with left ventricular failure or chronic lung disease were excluded, there was no significant difference in pulmonary vascular hemodynamics and all of these values were normal. In 21 patients who initially had normal pH but subsequently developed acidemia (9 patients, mean reduction in pH 0. 13 ± 0.03) or alkalemia (12 patients, mean increase in pH 0.10 ± 0.01) there was no significant correlation between changes in pH and pulmonary hemodynamic values. Among 26 patients with acidemia, those with lactic acidemia (lactate> 2.0, mean 7.70 ± 1.0 mM f L, mean pHa 7.27 ± 0.01 , 19 patients) had a significantly higher PVR (PVR 216 ± 24 vs 120 ± 24 dynes sec cm- 5, P < 0.05) than those with lactate ~ 2.0 ml\1 1L (mean 1.36 ± 0.0 I mM f L. mean pHa 7.29 ± 0.02, 7 patients) . This was attributable to significantly lower (P < 0.05) CO (4.4 ± 0.5 vs 6.2 ± 0.7 L fmin). The relationship between pulmonary hemodynamic values and PaC0 2 also was analyzed. Patients were categorized as: I) hypercapneic (PaC0 2 > 45, mean 51.4 ± 1.9 torr, 26 patients) and 2) hypocapneic (PaCO~ < 35, mean 29.7 ± 0.7 torr, 37 patients). Except for PADPPA WP, which was larger in hypercapneic P (6.9 ± 0.7 vs 5.1 ± 0.6 torr, P < 0.05), there were no significant differences between the two groups. We conclude that acidemia or alkalemia, and hypercapnia or hypocapnia, even when marked, do not in themselves account for abnormalities in pulmonary hemodynamics in critically ill patients. Physiologic, Radiographic and Pathologic Correlations in Diffuse Restrictive Pulmonary Disease. Ronald Fine; Marvin I. Schwarz; Ray E. Stanford; Giles F. Filley Resting and exercise gas transport data, chest radiographs, and lung biopsy slides were reviewed for seven patients with diffuse interstitial fibrosis (group I), four with interstitial pneumonitis (group 2), and five with sarcoidosis (group 3). All chest radiographs were characterized for extent, distribution, and patterns of disease by a single observer who had no prior knowledge of either gas transport or biopsy data. Biopsy slides were similarly reviewed for morphology and diagnostic accuracy. Group I had the lowest mean resting and exercise Pa02 and steady state carbon monoxide diffusion capacities (DLCO •• u-which equates mean alveolar CO with end tidal CO) , the highest resting and exercise PaC0 2 , the greatest arterial oxygen desaturation on exercise, and the most advanced disease radiographically. Group 2 exhibited similar but less severe and more variable physiologic and radiographic patterns. Group 3 demonstrated normal resting and exercise blood gases, minimally decreased resting DLCO •• n, and moderately advanced radiographic disease.

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In all groups there was at least a 50 percent increase in D .. CO •• n on exercise despite significant exercise arterial oxygen desaturation in groups I and 2. We conclude that in our series of patients CO~ retention is not clinically significant, o ..co .. ll may increase on exercise while Pa02 falls, physiology, radiology, and pathology correlate fairly well in diffuse fibrotic lung disease, and granulomatous disease tends to be more severe radiographically than physiologically. Evidence for the Cardioselectivity of Tolamolol versus Propranolol in Asthmatics. Gerald M . Fleming; Edward H . Chesler: Howard]. Schwartz. The use of propranolol in the management of angina pectoris and cardiac arrhythmias is increasing. However, propranolol increases airway resistance significantly in patients with asthma . Other available beta-adrenergic blocking agents either lack cardioselectivity or possess direct myocardial depressant effect or intrinsic sympathomimetic activity which make them less desirable in patients with coronary artery disease. Tolamolol is a cardioselective beta-adrenergic blocking agent without direct membrane depressant effect or intrinsic sympathomimetic activity. To assess the comparative effects of tolamolol and propranolol on airway dynamics, we studied 15 patients with asthma of mild to moderate severity. All subjects gave current histories of episodic wheezing and demonstrated significant improvement in airway resistance (Raw) following isoproterenol administration. On three subsequent days. the subjects were given tablets of propranolol 40 mg. tolamolol 50 mg or tolamolol 100 mg in a random entry, double-blind crossover protocol. Airway changes were determined by spirometry, How-volume loops and body plethysmography; and cardiac effects, by pulse, blood pressure, and serial electrocardiography, for six hours following dosage. All three agents lowered heart rate and pulse-pressure product to a similar degree. There was no significant change in pulmonary function with tolamolol 50 mg. However, propranolol 40 mg and tolamolol 100 mg both increased airway resistance significantly (P < .01) compared to tolamolol 50 mg. Previous studies show that tolamolol 50 mg is therapeutically equivalent to propranolol 40 mg in cardiac beta-adrenergic blocking activity. We conclude that tolamolol 50 mg demonstrates cardioselectivity and has a negligible effect on airways in asthmatics. Therefore, tolamolol 50 mg is the drug of choice in asthmatics who may require a beta-blocking agent. Early Diagnosis of the Adult Respiratory Distress Syndrome. Sanders T. Frank; S. Eugene Margolis; Martin McCurdy; Peter Philips Early recognition of the adult respiratory distress syndrome (ARDS) is mandatory if the high mortality rate associated with roentgenographic diagnosis of this entity is to be avoided. Noninvasive impedance plethysmorgraphy and the alveolar-arterial oxygen (A-a0 2) difference are two easily applicable monitoring modalities that will detect interstitial fluid accumulation before diffuse pulmonary infiltrates become roentgenographically present. Thoracic impedence plethysmography and A-a 0 2 differences were monitored in a series of postcardiac sur-

412 41ST ANNUAL SCIENTIFIC ASSEMBLY

gical patients where the ARDS was considered a potential complication. In patients without other pulmonary diseases, a fall in impedance was accompanied by a widened A-a 0~ difference and a fall in Po-!. When impedance fell over I ohm, the A-a 0~ widened although the amount varied between patients. Diuretic therapy or PEEP initiated for a falling impedance or a rising A-a 02 difference, resulted in an increase in impedance and Po 2, and a decrease in the A-a 02 difference. No clinical or roent· genographic pulmonary congestion occurred, and the ARDS was avoided. Impedance plethysmography is a noninvasive, easily applicable method of detecting the early accumulation of interstitial fluid. The associated widening of the A-a 0 2 difference and fall in J>o-2 in the presence of a normal xray film confirm the interstitial edema. Appropriate therapy can be initiated early, avoiding continued fluid accumulation and concomitant alveolar disruption . Experience with Pulmonary Resection in Cystic Fibrosis: Report of 14 Cases. R . C. Frates, Jr. ; G. 1\1. Harrison ; C. W. Ewing; D. K. Seilheimer Over the last I 3 years, we have treated 14 patients who have come to lobectomy or pneumonectomy as a consequence of the pulmonary complications of cystic fibrosis. Complications were rare. Indications for the procedure were similar to those of previous researchers. Preoperative management, however, differed in several important respects: a) tracheostomy was never performed (Schwachman and Schuster argue that tracheostomy is necessary), b) bronchography was both benign and helpful in assessing bronchiectatic areas not apparent on plain chest roentgenograms (this is contrary to both Mearns and Schwachman and Schuster; c) pa· tients undergoing surgery at this Center were hospitalized for a much briefer time preoperatively than the 4 weeks recommended by Mearns. Criteria used to evaluate the success of the procedure included pre- and postoperative comparisons of the frequency and length of hospital admissions and the examiner's impression of the patient's condition. Interpretation of the results is that some patients were greatly improved and none was worse after surgery. There is, however, an obvious need for clearer indications than now exist for this type of surgery. possibly based on matched controls and long-term followup. A Standardized Method for the Description, Recording, Retrieval and Analysis of Coronary Artery Lesions and Left Ventricular Wall Motion: Nine Years' Experience. Goffredo G. Gensini; Ann E. Kelly: Cathy Sunny Coronary arteriography and coronary bypass graft surgery are performed on an evergrowing number of patients. The accumulation of clinical, arteriographic and surgical data will remain practically meaningless as long as no standardized method exists for the description, recording, storage, and retrieval of this information . Over a nine-year period we have developed and refined such a method, based on mark sense cards and a dedicated computer. Files on 2,500 patients have been stored to date. Retrieval is performed in a conversational mode by way of a keyboard. Information can be collected and reported in English or in other languages by using multi· lingual cards and computer phrase files. Versions of these

CHEST, 68: 3, SEPTEMBER, 1975

programs translating several European languages to English and vice versa were planned. The German, Italian, Spanish and Portuguese versions are already operational; a French, translation is being implemented. The Hazards of Atropine Premedication for Bronchoscopy: A Preliminary Report. W . E. Goeller; D. D. Briggs, ]r Premedication of patients with atropine prior to bronchoscopy has been advocated to reduce secretions, to block reflex bronchospasm from tracheobronchial irritation and to protect against vagal induction of hemodynamic instability. Three patients receiving atropine prior to fiberoptic bronchoscopy experienced bradycardia with serious consequences. One developed marked hypotension: the second had a focal seizure; the third sustained a myocardial infarction. The following study was devised to evaluate the effect on heart rhythm and possible consequences of atropine. In II patients premedicated with 60 mg IJ\-1 codeine for fiberoptic bronchoscopy. atropine 0.8 mg was given IV during continuous ECG monitoring. None had ECG evidence of abnormal conduction. In seven patients (7 1II) transient slowing of the heart rate (averaging I3.6 bpm) preceded acceleration in heart rate. Seven (7 1II) demonstrated some degree of A-V dissociation while five patients (51II) developed transient junctional rhythm. Two patients had no rate ( < 3 bpm) and no rhythm change within the three minutes following the IV atropine. While the transient parasympathomimetic effects of atropine are known, these effects have not been considered clinically significant. These preliminary data show atropine can induce rhythm disturbances which may be related to untoward reactions during premedication for bronchoscopy. Routine premedication with atropine deserves critical review. Use of Positive Airway Pressure without Tracheal Intubation in Spontaneously Breathing Patients. D . M. Greenbaum ; ]. E. Millen ; B . Eross;]. V. Snyder; Ake Grenuik; Peter Safar Continuous positive airway pressure (CPAP) has been used successfully in adults and neonates with respiratory distress. Face and head chambers are available for infants so that CPAP can be delivered without tracheal intubation . We evaluated the results of CPAP therapy using a tightly-fitting face mask in 24 adult patients with inadequate arterial oxygenation despite toxic concentrations of inspired oxygen . Success rate in these patients was 58 percent, with those under 40 years of age in pulmonary edema of noncardiac origin having the best results. Success was judged by the ability of the technique to improve arterial oxygen tension to the extent that tracheal intubation and mechanical ventilation could be avoided. Complications were observed in six patients, with death from ventricular fibrillation in one, and C0 2 retention requiring cessation of the technique in another. Pneumothorax, pneumomediastinum, gastric dilatation, and skin lesions due to the face mask were also observed, but these did not require that the mode of therapy be discontinued. Experience with the technique indicates that it is useful in the management of certain patients with venous ad-

CHEST, 68: 3, SEPTEMBER, 1975

mixture of arterial blood due to alveolar collapse or edema. The avoidance of tracheal intubation is an important advantage in that the attendant high risk of infection is not seen. CPAP therapy with a face mask is therefore indicated for use in alert, cooperative patients with adequate breathing volumes who are unable to oxygenate arterial blood adequately without prolonged use of toxic levels of Flo2. Lung Cancer: Immunologic Effects of Surgery and Radiation Therapy. Nicholas ]. Gross; B . Berger; Tom R . De Meester Current concepts of tumor immunology suggest that the thymus-derived lymphocyte system, cell-mediated immunity, is important in the defense against cancer cells. Lung cancer patients are known to be relatively immunosuppressed and are frequently anergic. In the present study, the immunologic effects of surgery and radiation for lung cancer were investigated. Preoperative studies confirmed that lung cancer patients have impaired PHA responses and E-rosette testing. Immediately following surgical resection of the tumor there was a further decline in these parameters to about half the preoperative level. After 4 days, lymphocyte reactivity increased to a peak at about I4 days which was within the range of normal noncancer subjects following which it gradually declined over the next several weeks towards preoperative levels. Patients who received radiation therapy to the mediastinum showed a progressive dose-related decrease in all parameters of lymphocyte function, and were severely immunosuppressed by the end of treatment (6,000 rads) to the mediastinal region. There was little if any tendency for recovery of immune responses up to 5 weeks after the completion of radiation therapy. These results indicate that aspects of the therapy of lung cancer, particularly radiation therapy. may have deleterious effects on intrinsic antitumor mechanisms, and suggest that ways to avoid these effects, possibly by immunotherapy. should be sought. Pulmonary Embolism: Correlation of Lung Scanning and Pulmonary Arteriographic Findings. N. Harlaftis; A . C. Gonwlez; W . ]. Waldo; P. N. Symbas Perfusion lung scanning has been considered a fairly conclusive test for the diagnosis of pulmonary embolism and the institution of all forms of therapy except for pulmonary embolectomy. During the last four years, 67 patients with strong clinical history of pulmonary embolism underwent chest x-ray examination, perfusion lung scanning and pulmonary arteriography. The diagnostic validity of these tests has been compared. In 48 of the patients with perfusion, lung scan was reported as being compatible with pulmonary embolism and in the remaining I9 was questionable. Of the 48 with positive lung scan, II had arteriograms reported negative for pulmonary embolism and four were questionable. Of the I9 patients questionable for pulmonary embolism lung scan, I2 were reported as having negative pulmonary arteriogram and two questionable findings. This study suggests that a large segment of patients with strong clinical history of pulmonary embolism and pulmonary scan compatible with this clinical picture have no demonstrable pulmonary emboli on pulmonary

41ST ANNUAL SCIENTIFIC ASSEMBLY 413

arteriography. Stricter imerpretation of the chest x-ray film findings and perfusion scan may minimize the false reading. but still this high incidence of false positive lung scans calls for confirmatory pulmonary angiography when interruption of inferior vena cava is indicated. Bypass Surgery for Prinzmetal Angina. Eric E. Harrison; Willie IV. /Jell; Sheldon S. Sbar; Luis N . Bessone; Dennis F. Pupello ; Richard H . Blank l'rim.mctal angina (PA) is a clinical electrocardiographic syndrome. Six cases of PA were seen from July, 1!172 to July. 1974 . All had well documemed ST segment elevation during chest pain and two-thirds had arrhythmias during pain. Age range was 46-66 years. Onethird had angina for greater than 3 months. All electrocardiograms showed no infarction patterns. Left ventricular contractility was normal in all but one. T••·o-thirds had significa nt single vessel disease, 3 involving the left anterior descending (LAD) coronary artery, and one involving the right coronary artery (RCA) . Two patients had significant 2 vessel disease, one of the LAD and RCA, the other of a diagonal and diffuse involvement of the RCA. Five patients underwent aortocoronary bypass sur. gery. Follow-up period ranges from 4 to 28 months with a mean of 15. One patient had postoperative acquisition of new q waves, but was stable without problems. All five are asymptomatic and have normal ECGs. The patient with diffuse RCA disease did not have bypass surgery, has a nonnal ECG and is asymptomatic on propranolol after a 16 month follow-up. Coronary artery bypass surgery is particularly promising in this syndrome. Quantitative Differences in Airway Morphology Secon· dary to Sexual Function. M . Hayashi ; P. Phelps; Gary Huber In humans, men appear to be more susceptible to airway injury from tobacco inhalation, air pollutants and other factors. The cause of higher morbidity rates in human men than women from diseases of the respiratory tract may be a complex one involving several factors. To study this experimentally, 13 male and 45 female (15 each in proestrus, estrus and diestrus) CD rats weighing around 250 gm were evaluated. Tracheas were fixed in situ by injection of a mixture of formaldehyde and glutaraldehyde. Longitudinal sections cut from paraffin blocks were stained with combined alcian blue (pH 2.6) and periodic acid Schiff (PAS) to count goblet cells or with hematoxylin and eosin to determine epithelial thickness. In the normal rat trachea , cells containing PASpositive granules at their apexes constituted a major population of goblet cells. The presence of these goblet cells in the trachea was greater in females than in males. Proestrus and estrus females contained significantly more goblet cells of this type than did males. However, diestrus females did not differ significantly from males. In females, estrus rats contained significantly more of these goblet cells than did diestrus animals. The tracheal epithelium of male rats was significantly thicker than that of estrus females, but did not always differ significantly from proestrus and diestrus females. These studies demonstrate that airway morphology differs in males and females and varies in the female as a function of hormonal cycles. These results raise the question that similar differences may be important in the pathogenesis of human disease and deserve further clarification in man.

414 41ST ANNUAL SCIENTIFIC ASSEMBLY

Surgical Treatment of Pectus Excavatum and Pectus Carinatum. William H . Heydorn; Russ Zajtchuk ; George Schuchmann; Tracy E. Streuey The surgical treatment of pectus deform ities remains a controversial topic. A variety of surgical techniques have been advocated and utilized. Seventy-one patients with pectus excavatum underwent surgery. Fifty-nine have been followed up for over 5 years. Results are good in 44, fair in 17, poor in 7 and ~ were lost to follow-up. Results were not related to age but were related to the type of operative procedure. Thirty-two of 44 patients in whom metallic, internal support was used had a good result. Nine of 16 patiems had a good result without a strut but with other forms ol internal stabilization. Techniques which did not usc sternal stabiliz;ttion or relied on external support devices were unsatisfactory. The late results obtained by totally excising deformed cartilages, mobilizing the sternum , anterior osteotomy and internal metallic support have been most satisfactory and have been associated with low morbidity a nd no mortality. Sixteen patients with pectus carinatum underwent corrective surgery. Thirteen have been observed for 5 years. Results were good in 15 and fair in I. The late results obtained by removal of deformed cartilages, sternal mobilization, sternal osteotomies as indicated and reefing of the perichondrial beds have been good with little morbidity and no deaths. The incidence of good results found on long-term follow-up has led us to recommend repair in most patients with pectus deformities who desire correction. Repeat Surgical Procedures for Myocardial Revascu· larization. james F . Hoffman, Jr.; Richard T . Shore; IV. Dudley johnson Seventy-five patients have undergone from I to 4 previous myocardial revascularizations. The reasons for repeat surgery have been recurrent angina as the result of inadequate previous Vineberg procedures. unsuccessful Beck procedures, early and late saphenous vein graft closure, vein patd1 failure, incomplete initial revascularization, and progression of disease in coronary arteries other than those previously bypassed. Angiography is essential in determining whether recurrent symptoms are due to graft closure or progression of disease. If the problem is late graft closure, information regarding the initial graft How measurements and the condition of the recipient myocardium is of great help in determining the feasibility of secondary surgery. Technical problems are of considerable significance in repeat procedures with the different coronary arteries having different degress of accessibility. Technical aspects of handling the initial procedures, as well as the sccon· dary procedures, so as to facilitate and increase safety, will be discussed in detail. Pulmonary Function Measurements in Unsedated Subhuman Primates. james M . Huey ; Lester R . Bryant A primate smoking model has been developed to simulate human tobacco smoking experience, and the smoking colony has been populated with adolescent stumptail monkeys (Macaca speciosa, 3-6 kg) . As a corollary to model development, verification of smoke inhalation and

CHEST, 68: 3, SEPTEMBER, 1975

determination of smoke effects mandated the development of pulmonary function tests in the unsedated animal. Sufficient cooperation has been elicited to perform nitrogen washouts, and to measure airways resistance and dynamic compliance. For studies, the animal is restrained in a primate chair and fitted into a mask which has a dead space of 15 ml and enforces mouth breathing. Thoracic pressure measurements are obtained via a nasoesophageal catheter which can be passed with minimal resistance from the animal. A pneumotach attached to the mask breathing port yields flow measurements which can be integrated to obtain tidal volume. Signals are transduced, amplified and displayed on an X·Y oscilloscope. Pressure-flow and pressure-volume plots yield resistance and compliance data. Average values of 1-5 mm Hg j L jsec and 0.03 L f mm Hg have been obtained from baseline studies of 12 animals. For washout studies the animal is attached directly to a nitrogen analyzer and logarithmic nitrogen concentration and tidal volume are recorded. Total washout volume is remarkably constant ior individual animals, and a simple bellows model of the lung is adequate to describe present data. Failure of Demand Pacing with Small Surface Area Electrodes. H . C. Hughes , ]r.; R . R . Brownlee; G. F. 0 . Tyers As pacemaker electrode stimulating area is reduced, the energy required for pacing the heart falls dramatically. However, little information is available on the effect of surface area on a lead's ability to sense R-wave potential (R WP). Ten dogs were anesthetized and acid-base balance and electrolytes were maintained within normal limits. Through a right thoracotomy, intramyocardial left ventricular and endocardial (E) right ventricular pacemaker electrodes were placed for oscilloscopic RWP measurements (millivolts) . There was a high correlation between surface area and RWP : myocardial r .86, endocardial r .85 (both P<0.025). The Cordis 4 mm result is lower than expected, but with E placement only the tip of this long, thin electrode contacts the myocardium. Clinically we have measured even lower acute RWPs with the BT (-3.5±0.8) n = 15. These results demonstrate that in addition to the beneficial effect of lower pacing thresholds we and others have previously shown with small surface area electrodes, a detrimental effect occurs. Lower R WPs are detected as surface area is reduced and this can result in failure of the demand mode with reversion to fixed rate pacing. This complication has been noted with increasing frequency since the clinical introduction by Cordis and ESB of small surface area electrodes and indicates the need for design modifications.

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Effects of Sympathetic Adrenergic Denervation (6-Hy· droxydopamine) on the Pulmonary Hypertension Asso· dated with Distention of the Main Pulmonary Artery in the Conscious Dog. james A. jengo; Craig E. ]uratsch; Michael M. Laks Recently, we have described a pulmonary reflex which links distention of the main pulmonary artery (MPA) with the production of pulmonary hypertension. A triple lumen balloon catheter (Edwards) was designed to distend the MPA and measure simultaneous right ven-

CHEST, 68: 3, SEPTEMBER, 1975

tricular and pulmonary artery pressure in the conscious dog. In order to determine the extent that the sympathetic nervous system participates in the production of the observed pulmonary hypertension, this reflex was studied before and 18 hours following intravenous infusion of 6-hydroxydopamine (6-0HDA) . 6-0HDA is known to cause sympathetic denervation by selectively destroying adrenergic nerve terminals, liberating and depleting norepinephrine. 6-0HDA (10 mg j kg) was infused into a peripheral vein during a period of 4 to 6 hours. Total sympathetic adrenergic blockade of the conscious dog was assumed when a 50 mg dose of 6-HDA infused in 5 minutes no longer resulted in an increase in systemic arterial pressure. In four dogs, distention of the M PA caused an increase in pulmonary artery pressure from 19 / 4 to 39 f ll mm Hg (P<0.02). After infusion of 6-0HDA , distention of the MPA did not produce a significant change in pulmonary artery pressure, 19f6 to 23 / 6 (P>0.2). Therefore, these data suggest that the sympathetic adrenergic nervous system contains the efferent limb of the pulmonary hypertension reflex. Of din· ical importance, the sympathetic nervous system may participate in the pathogenesis of pulmonary hyperten· sion observed in humans. Long-Term Follow-Up of Tricuspid Annuloplasty (1960· 1975). jerome Harold Kay; A. M . Mendez; Pablo Zubiate Tricuspid annuloplasty was performed in 98 patients with pure tricuspid insufficiency from 1960 to 1975. All patients were in class 3 or 4 of the New York Heart Association classification (NYHA class) . All had significant mitral valve disease with the following distribution: mitral stenosis, 41; mitral insufficiency, 13; mitral insufficiency and stenosis, 44. Eight patients had signifi· cant aortic valve disease as well, and two had an atrial septal defect (ASD). Of these 98 patients, 8 had mitral annuloplasty; 16 had mitral commissurotomy; and 74 had mitral valve replacement. Seven also had aortic valve replacement. One had aortic annuloplasty; two, aortic commissurotomy; and two, repair of an ASD. There were 16 hospital deaths (16 percent) , but only 4 deaths in last 52 patients (8 percent) . Tricuspid insufficiency recurred in 12 (12 percent), requiring further surgery. In these 12 patients there was primary failure of mitral and jor aortic surgery. There were 8 late deaths (8 percent) . Actuarial studies revealed a 63 percent survival rate at 15 years. The patients surviving the original operation are in NYHA class 2. The results of tricuspid annuloplasty have been functionally satisfactory, except for the patients in whom mitral and j or aortic valve surgery failed. When properly performed, tricuspid annuloplasty appears superior to replacement for the management of severe pure tricuspid insufficiency. Carboxyhemoglobin Levels in Human Subjects in a Tunnel Located at 11,000 Feet. David L. Kelble; Don Sorrels; Charles Bray; David Slosky Carboxyhemoglobin levels were determined in 22 subjects in a vehicular tunnel at 11,000 feet in the Colorado mountains. The carboxyhemoglobin levels were determined prior to entry into the tunnel and at 15, 30, and 45 minutes within the tunnel during an extremely busy

41ST ANNUAL SCIENTIFIC ASSEMBLY 415

Sunday afternoon when the number of vehicles passing through the tunnel was at a maximum. Eleven subjects were nonsmokers, 10 were studied at rest and I while exercising. Eleven subjects were smokers, and 10 were studied at rest and I while exercising. The carboxyhemoglobin levels are presented prior to entry into the tunnel and show rather striking elevation in the smokers. During the 15, 30, and 45 minute samples, the rise in carboxyhemoglobin is described for the smoking group and the nonsmoking group. Details are presented in regard to ventilation requirements for tunnels at this altitude with reference to the combined effect of decreased oxyhemoglobin secondary to reduced Po2 and hemoglobin unavailable because of combination with

co.

Continuous Positive Airway Pressure as a Substitute for Mechanical Ventilation in Intubated Adults in Acute Respiratory Failure with Severe Hypoxemia without Hypercapnia. Faroque Khan; Errol Hunte Continuous positive airway pressure (CPAP) is widely used in the management of premature infants with hyaline membrane disease. CPAP increases functional residual capacity. decreases V/Q abnormalities secondary to alveolar collapse, with resulting increase in Pa02 and reduction in the FI02. We have studied the efficacy of CPAP in 7 selected adult patients with ARDS or stiff lung syndrome of multiple etiologies with severe hypoxemia who were hypocapniac or eucapnic, with a vital capacity greater than 10 mljkg. Each of these patients was receiving mechanical ventilation, as treatment by T-tube alone required Flo-~ over 60 percent to maintain satisfactory Pa02. Technically CPAP is quite easily carried out. The pressures used ranged from 2-10 em of water for durations of up to 48 hours. There were no complications and no significant hemodynamic changes during the period of CPAP use. In all seven patients there was a marked increase in Pa02 on CPAP ranging from a minimum of 10 mm to a maximum of 196 mm, with a mean of 60 mm Hg. Also noted was a rise in PaC02 ranging from 3 mm to 16 mm with a mean of 10 mm Hg. The drop in pH was minimal. Thus, it appears that CPAP is useful in patients with ARDS who manifest hypoxemia without hypercapnia. This treatment eliminates the need for either mechanical ventilation with its high peak airway pressure and risk of tension disorders, or the need for high Flo-~ to achieve adequate oxygenation in the patients on T-tube. Use of Gallium Scan to Predict Inflammatory Activity in Diffuse Interstitial Lung Disease. M . Khurana; F. S. Mishkin; A . H .Niden Pulmonary inflammatory reaction (potentially reversible) may be difficult to distinguish from fibrosis (irreversible) when patients with diffuse interstitial lung disease (DILD) are first observed . Since 67gallium citrate accumulates in cellular reactive processes, the value of gallium lung scan (Ga) was investigated in such a clinical setting to assess the inflammatory activity of the process. Ten patients with roentgen and clinical findings of DILD were studied. All had Ga. pulmonary function studies and percutaneous needle biopsy (9) or open lung biopsy (I) . Inflammatory activity of the process as assessed by

416 41ST ANNUAL SCIENTIFIC ASSEMBLY

roentgenogram and Ga was correlated with pathologic changes. Six patients had sarcoidosis, two usual interstitial pneumonia, one scleroderma and one siderotic fibrotic nodules. Ga accurately assessed the degree of pulmonary inflammatory reaction, being abnormal in those patients with an active process. In the two patients with pulmonary fibrosis and little if any reactive process, Ga was normal. In contrast there was poor correlation between interpretation of roentgenographic evidence of activity and pathologic findings. Two patients with active sarcoidosis and abnormal Ga had follow-up after treatment. Ga became normal and correlated with clearing ot the chest roentgenogram. The study indicates that Ga, a noninvasive procedure, correlated with chest roentgenogram may be useful in assessing the relative degree of pulmonary inflammation vs fibrosis in patients with DILD. Ga may also be of value in following the disease in these patients whether or not treatment is instituted. Plug Closure of Patent Ductus Arteriosus without Thoracotomy. Soichiro Kitamura; Kenji Sato; Yasuaki Naito; Masaoki Fujino; Takahiro Kozuka; Choken Oyama; Yasunaru Kawashima; Hisao Manabe Plug closure of patent ductus arteriosus (PDA) without thoracotomy (Porstmann method) is now feasible for selected patients with minimal risk. We report our experiences with this method in 75 consecutive patients ranging in age from 3 to 38 years. Successful closure was attained in 72 patients with a success rate of 96 percent. There was no mortality in the current series and the failure in 3 was due to the distensible oversized ductus. Although the method utilized was essentially the same as that introduced by Porstmann in 1968. some instrumental and technical improvements have been made with an increasing success rate, less blood loss and less time needed. A single catheter method was also devised, in which a loop wire or a catching wire was no longer required. Bleeding was minimal and the time required for this procedure was usually less than 3 hours. Aortagraphic classification of PDA into 3 morphologic features has greatly served in designing a plug of suitable size and shape for each ductus. Complications were rare or minimal, if any, but can be serious if the plug falls into the aorta and becomes lodged above the renal artery after a track wire has been removed. This occurred in I patient resulting in acute renal failure. The transfemoral catheter method for dosing PDA is reliable and has certain advantages over thoracotomy. We believe that this is the treatment of choice whenever indicated and cautiously performed. Transbronchial Lung Biopsy via the Fiberoptic Bronchoscope in Sarcoidosis. C. H. Koontz; Lee Roy Joyner; Roald A. Nelson In a prospective study at two medical centers, 42 consecutive patients suspected of having thoracic sarcoidosis without prior tissue confirmation underwent transbronchial lung biopsy (TBB) via the flexible fiberoptic bronchoscope. TBB was positive (noncaseating granulomas demonstrated in lung andfor bronchial tissue) in 23 of the 38 cases (61 percent) in which adequate tissue was obtained. Special stains and cultures for acid-fast bacilli and fungi were negative in these cases and sarcoidosis was subsequently diagnosed in all 42 cases in this series.

CHEST, 68: 3, SEPTEMBER, 1975

Positive TBB was obtained in II of 20 cases (55 percent) with radiographic stage I disease; in IOof 15 cases (67 percent) with stage 2 disease; and in 2 of 3 cases with stage 3 disease. There was a higher probability of a positive TBB in patients with dense parenchymal infiJ. trates, bronchial symptoms such as cough, hemoptysis or wheezing, and in those with a reduced FEV1 . There were no significant complications from the procedure. One patient sustained a small pneumothorax which spontaneously resolved. We feel that TBB via the flexible fiberoptic bronchoscope is an attractive initial procedure in suspected cases of sarcoidosis where tissue confirmation is desired. It is safe, well tolerated, and can be easily performed by any trained fiberoptic bronchoscopist with advantages over liver biopsy and mediastinoscopy. Susceptibility of the Emphysematous Lung to Oxygen Toxicity. D. M . Kovnat; P. Kory; Gordon L. Snider;]. S. Brody High concentrations of inspired oxygen produce pulmonary injury which is characterized by inflammation, capillary endothelial damage, pulmonary edema and death . Interspecies variation in susceptibility to this injury has been noted by others; whereas rats developed protective enzymes when previously exposed to 80 percent oxygen, hamsters did not. The protection conferred by prior lung injury is less well understood . We studied the modulating effects of prior pulmonary disease on suscep· tibility to injury from 100 percent oxygen by comparing lnmsters with emphysema induced by a single instillation of porcine pancreatic elastase 65 days earlier than normal controls. Lung washings revealed a similar pattern of injury in both groups with an increase in leukoqtes and macrophages within 24 hours of exposure and progressive appearance of large molecular weight proteins. Histologic sections confirmed the presence of inflammation and edema after 5 days of exposure. The mortality in control hamsters was 20 percent after 3 days and 90 percent after 5 days of 100 percent oxygen; mortality of the hamsters with emphysema, however, was zero after 3 days and only 10 percent after 5 days. Morphometric analysis of the lungs of the elastase-treated animals revealed nonuniform distribution of both emphysema and edema. The areas of lung with greater dilatation of airspaces remained relatively free of edema. There was a uniform distribution of edema throughout the lungs of the animals without emphysema. The lungs of normal hamsters and those with elastaseinduced emphysema are equally susceptible to the toxic effects of oxygen, as measured by lung-wash cellular and protein response. The protection from death conferred upon the animals with emphysema is probably related to the presence in them of areas of lung which are relatively free of edema. The sparing of these emphysematous areas of exudation of fluid and protein may be due to regional biochemical or regional structural alterations, the latter perhaps resulting from differences in surface tension. Detection of Arrhythmias in Prolapsing Mitral Valve Syndrome. Kent Kreisman; Robert Kleiger; Brent Parker Cardiac arrhythmias in patients with mitral valve prolapse are now known to occur in a high proportion of patients. Both atrial and ventricular arrhythmias are

CHEST, 68: 3, SEPTEMBER, 1975

common. Many patients whose normal electrocardiogram fails to demonstrate rhythm disturbances exhibit arrhythmias either on exercise andfor on long-term monitoring using Holter monitoring. We have now studied 57 patients with click systolic murmur syndrome proved by either catheterization or by typical echocardiographic abnormalities. Forty-two (74 percent) were women and 15 (26 percent) were men. All patients had either 24- or 10-hour Holter monitoring or maximal stress tests using the Bruce method. Thirty-five patients had both Holter and stress tests. Eighty-one percent of patients had ventricular arrhythmias on Holter monitoring and 15 percent displayed ventricular tachycardia. Ten percent of the patients exhibited only atrial arrhythmias. In contrast, the percentage of patients demonstrating arrhythmias with exercise testing was only 56 percent. Nine patients who revealed ventricular arrhythmias on Holter monitoring had none on stress tests. Two patients with ventricular arrhythmias on stress test had none on Holter monitoring. However, some patients experienced more complex arrhythmias with exercise than on Holter monitoring. Holter monitoring in patients with prolapse shows a very high frequency of ventricular arrhythmias and appears to be a more reliable method of detecting them than stress testing alone. A combination of both is desirable because of the finding of more complex arrhythmias by stress testing. Extracorporeal Membrane Oxygenation (ECMO) as a Treatment for Massive Pulmonary Thromboembolism. Daniel ]. Krellenstein ; Christopher IV. Bryan-Brown ; jennifer Hanns; E. Converse Peirce, II l\'fassive pulmonary thromboembolism remains a serious threat to the lives of many patients. This study was undertaken to determine if ECMO could modify the effects of massive embolism so that survival was possible. Twenty anesthetized mongrel dogs (20-30 kg) were prepared for venoarterial perfusion with a demand pump (Sl\IEC) and a membrane lung (GE) and perfused slowly for 1.5 hours to moderate any homologous blood shock. Subclavian artery and thermodilution Swan-Ganz catheters were used for sampling and monitoring pres· sures and cardiac output. Tantalum-impregnanted thrombus (1-1.5 mlfkg, 24 hours old) was injected intravenously. On a random basis, half the dogs were perfused for 4 hours. Each hour the perfusion was stopped to assess cardiopulmonary status. Control animals received standard resuscitative measures. Survivors were studied on the sixth day and sacrificed. Clots were followed with AP and lateral chest radiographs. Postmortem examinations included histologic studies. Dogs were profoundly hypotensive with an elevated pulmonary pressure (systolic, 74. 1 ± 5. 7 mm Hg) immediately after the embolization. Controls generally died within 15 minutes. ECMO flow was about 2 liters j min and provided satisfactory cardiopulmonary support. Extracorporeal membrane oxygenation not only can maintain an animal who would otherwise die quickly of massive pulmonary thromboembolism, but such support. even though temporary, can greatly improve the chances of survival.

41ST ANNUAL SCIENnFIC ASSEMBLY 417

Diagnostic Accuracy in Lung Cancer: A Comparison of Techniques Used in AS!lOCiation with Flexible Fiberoptic Bronchoscopy. Paul A. Kvale; Frederick R . Bode; SudhaKini :\ prospective study was conducted to determine if post· bronchoscopy sputum specimens (PBS) were still the most accurate method of diagnosing lung cancer as they had been when only the rigid bronchoscope was available. Flexible fiberoptic bronchoscopy (FFB) was performed 254 times in 228 patients ; 96 of these patients were ultimately proved to have lung cancer. Whenever possible, each patient had the following specimens submitted : bronchial brushings (B BRUSH), bronchial biopsy (B BIOPSY), bronchial brushings in saline (BB in S), bronchial washings (BW), and three PBS. In the latter part of this study. patients with peripheral tumors not visible through the bronchoscope were studied with the aid of biplane fluoroscopy. In this series using the FFB, B BRUSH yielded the highest percentage of positive specimens (64 percent) and were far superior to PBS (40 percent). BW and PBS did not add significantly to diagnostic yield and we conclude that they should no longer be part of the routine diagnostic tests used in association with FFB. In addition, we found biplane fluoroscopy to improve diagnostic accuracy when used in peripheral lesions not visible through the bronchoscope. Long-term Clinical Assessment of Patients with "In-Hospital Crescendo Angina" Treated by Emergency Vein Grafting. Cary ]. Lambert ; Ben F. Mitchel; Gerald F. Geisler; Maurice Adam; Aaron Estrera; ] . Peter Thiele Ninety-five patients treated by emergency vein grafting for "in-hospital crescendo angina" were surveyed. No patient has been followed up for less than two and onehalf years. There were 6 operative deaths (6 percent) and 7 late deaths (8 percent). Three of the operative deaths were patients who actually had had an acute myocardial infarction, two patients had left main artery obstruction, and one patient had a trapped first septal perforator. Only three of the late deaths were directly cardiac related; I, a myocardial infarction ; I, "intractable coronary artery insufficiency;" and I, ventricular fibrillation. Sixty-one patients are alive, angina free and fully productive. An additional 17 patients are decidedly improved and, albeit functional, with some angina requiring medical treatment. One patient is psychologically unbalanced despite normal restudies. Three were lost to follow-up. although one of these was asymptomatic in China at two and one-half years. We conclude that: I) "in-hospital crescendo angina" cannot always be differentiated from an acute myocardial infarction, 2) that a fully productive and a gainful life expectancy can be enjoyed after surgical revascul~riza­ tion, and 3) that the late attrition rate due to .cardiac cause has been reduced. Safety of Double Valve Replacement: Results of 100 Consecutive Cases. Gerald M. Lemole; Ugo F. Tesler; R. Cuasay; Javier Fernandez; Dryden P. Morse; Alden S. Gooch; Vladir Maranhao During the period October 1972 to April 1975, combined aortic and mitral valve replacement was performed

418 41ST ANNUAL SCIENTIFIC ASSEMBLY

in 100 consecutive patients with Bjork-Shiley and Beall valve prostheses with a total of three deaths. Over two thirds of the patients were in NYHA functional class 3 or 4 and were above 50 years of age. Valve calcifications were present in 75 cases. Fifteen patients had a history of peripheral arterial embolism. Closed or open mitral commissurotomy had been done previously in 12 patients. Besides improvements in pre- and postoperative medical management that significantly contributed to the decreased early and late mortality and morbidity in this series, particular importance is attributed to a new technique of insertion of the prosthetic valves which cuts ischemic time to a minimum. After hypothermic heartlung bypass is established and the heart cooled topically with iced saline solution, the aorta is cross-clamped and having performed a left atriotomy, the mitral valve is excised. The septal half of the prosthetic mitral valve cuff is sutured to the septal half of the mitral annulus with a continuous suture. An aortotomy is then performed, the aortic valve is replaced and the aortotomy is closed . At this point, the aortic cross-damp is released and the remaining half of the prosthetic mitral valve cuff is sutured with a continuous suture to the mural half of the mitral annulus and the atriotomy is closed. while the heart is perfused . The Specificity and Nature of Serum Angiotensin-Converting-Enzyme (ACE) Elevations in Sarcoidosis. jack Lieberman; Pilar Fiorio The detection of an elevated level of serum .-\CE activity appears to be a valuable test for confirming a diagnosis of active sarcoidosis. The mean level of activity in 172 adult controls is 7.6 ± 2.0 units j ml as compared to 15.01 ± 8.1 unitsf ml in 57 adult patients with confirmed active sarcoidosis; 48 of 57 patients had values greater than 2 SD above the control mean. Ten patients with resolved sarcoidosis and 14 of 16 receiving therapeutic doses of corticosteroid medication had normal levels of serum ACE activity. Three patients who were tested during the course of treatment with corticosteroids showed progressive reduction in ACE level into the normal range after 2 to 3 weeks' therapy. Other patients with various lung or granulomatous diseases including emphysema, asthma, lung cancer, tuberculosis, histoplasmosis, Coccidioides immitis and Hodgkin's disease had reduced or normal ACE activity in most instances. However, 3 individuals with Gaucher's disease had markedly elevated levels of serum ACE activity (46-84 units j ml serum) raising the possibility of a relationship between Gaucher's disease and sarcoidosis. Gaucher's could be differentiated by a coincidental elevation of serum acid-phosphatase and ACE activities. Speculation that the granuloma in sarcoidosis may be the source of the elevated serum ACE was tentatively confirmed by assaying an extract of sarcoid lymph node which had approximately 24 times more ACE activity than an extract of normal lymph node (0.748 units j mg tissue vs 0.031 unitsjmg tissue) . We conclude that an assay of serum ACE is valuable in the differential diagnosis of sarcoidosis, although patients with Gaucher's disease also have elevated serum levels. The source of serum ACE in sarcoidosis is most likely the epithelioid cells of the sarcoid granuloma.

CHEST, 68: 3, SEPTEMBER, 1975

Tracheoesophageal Anastomosis for Intractable Aspiration. Roger C. Lindeman Some unfortunate patients suffer disorders which in one way or another, usually neurologically, severely restrict the larynx in its role as a protector of the lower airway. Aspiration ensues and unless it can be successfully managed, repeated episodes of a violent pneumonitis may lead to terminal chest problems. In some patients, even the cuffed tracheostomy tubes of new and improved design do not adequately prevent aspiration over an extended time interval as evidenced by repeated bouts of aspiration pneumonia in spite of these cuffed tubes and in spite of optimal intensive care. For these patients with intractable aspiration, and in whom recovery is expected only after a prolonged period of time, we have suggested a diverting procedure which employs a tracheoesophageal anastomosis as an effective yet reversible solution. Such an anastomosis with concomitant tracheostomy allows aspiration of saliva and even food to occur through the malfunctioning larynx, hut diverts it back into the esophagus through the tracheoesophageal anastomosis. In normal mongrel dogs we demonstrated that an endto-side tracheoesophageal anastomosis is well tolerated and can be performed without damage to the intrinsic larynx or recurrent laryngeal nerves. The tracheoesophageal lumen remained patent and the anastomosis intact for as long as these animals were observed prior to. reconstruction. The reversibility of the tracheoesophageal anastomosis was demonstrated in these dogs by excising the anastomosis, repairing the esophageal defect, and restoring the continuity of the trachea by end-to-end anastomosis. Vocal cord motion remained intact; the dogs ate normally, and barked once again. A tracheoesophageal anastomosis was performed in a 60-year-old white woman who had suffered lower cranial nerve damage as a result of a large acoustic tumor and the excision thereof. Despite every effort to control aspiration, pneumonitis occurred and became fulminant. The diverting tracheoesophageal anastomosis was performed with relative ease and was well tolerated by the patient. Aspiration was totally and dependably controlled and no further chest complications occurred. Her nasogastric feeding tube was removed and she ate a regular diet with very little difficulty. She gained in strength, became much more alert mentally, and is now taking care of herself in a nursing home. We are following her progress by indirect laryngoscopy and barium-swallow examinations ; and at five months after anastomosis, we are possibly seeing the first signs of lower cranial nerve recovery. We hope that reconstruction and restoration of function will soon be possible. We f~el that the results to date of our animal experimentation and of our case report are satisfactory. Many questions remain unanswered, however, and for this reason we must emphasize a very conservative approach to the clinical application of this procedure.

Pulmonary Structure and Function Studies with Brominated Perfluorocarbon. D. M . Long; M. S. Liu; A. S. Arambulo; G. D. Dobben Radiopaque perfluorocarbon (RPF) is a biologically inert, chemically stable contrast agent developed spe-

CHEST, 68: 3, SEPTEMBER, 1975

cifically for pulmonary examinations. Emulsions of RPF are useful in obtaining bronchograms and cinebronchograms. Pure RPF is useful in obtaining alveolograms. Three healthy volunteers and 14 patients with pulmonary disease have undergone bronchography or cinebronchography with emulsions of RPF in a dosage of 24 to 45 ml. When indicated, simultaneous bilateral bronchograms were performed and were well tolerated. Two healthy volunteers and two patients with parenchymal pulmonary disease have had alveolograms. Pulmonary function studies, arterial blood gases and hematologic examinations have been performed before and after the x-ray studies. Biologic disposition studies have been performed in 5 subjects who had subsequent pulmonary resections. Radiographic studies with RPF indicate that this contrast agent is as good as or superior to available contrast agents. The material is well tolerated in patients with ad\·anced pulmonary disease. Valuable physiologic information on differential mucociliary clearance and ventilation can also be obtained with plain chest x-ray films. RPF is cleared by mucociliary clearance and vaporization, and prolonged retention of contrast material has not been observed. Distribution of Ventilation Measured by Breath Sounds. Robert G. Loudon; Sharon Balkenhol Radioactive xenon has been used extensively to study the regional ventilation . The presence, absence, or intensity of breath sounds are used by the clinician as an indicator of the presence or absence of ventilation, and sometimes as a rough guide to the adequacy of ventilation. Several factors other than ventilation influence the intensity of vesicular breath sounds, but the majority of these do not influence intensity at a given location over the chest. Changes in intensity with time during the respiratory cycle relate predominantly, although not entirely, to ventilation. We have developed methods for studying the time relationships between breath sounds recorded at different positions over the chest, and relating their intensity to one another during the different maneuvers. Ten normal subjects were trained in diaphragmatic breathing over a period of eight weeks. Recordings were made by microphones attached to the chest wall over the upper and lower part of the right lung, and simultaneous recordings of air flow at the mouth and volume change were made. The subjects were instructed to make a variety of respiratory maneuvers using thoracic and, subsequently, diaphragmatic breathing. These studies were conducted both in the seated and the supine postures. During inspiration from residual volume, using thoracic breathing in the seated posture, cross-correlation techniques show a time lag between the onset of breath sounds over the upper part of the lung and the lower part of the lung, the basal breath sounds lagging. By breathing diaphragmatically, the subjects could, after training, reduce the time lag to a significant degree. Measurement of sound throughout the respiratory cycle allows comparison of relative intensities in time for sounds recorded at the different locations, and their graphic representation. Again, differences are seen in the shape of the breath sound intensity curves, and these differences are changed by adopting diaphragmatic breathing.

41ST ANNUAL SCIENTIFIC ASSEMBLY 419

Influence of Aortocoronary Bypass (ACB) on Global and Regional Myocardial Metabolic Dysfunction. jack M. Mat/off; Kanu Chatterjee ; Hector Sustaita ; H . J. C. Swan Arterial and coronary sinus venous blood sampling (18 patients) and. in addition , simultaneous anterior interventricular venous blood sampling (5 patients) for determining global (G) and anterior wall (R) myocardial 02 (A-V02) and lactate (%L) extraction were performed at rest (C) and during atrial pacing (P) before and after successful ACB. All patients had angina preoperation with pacing. Sixteen patients were free of angina after surgery during pacing, despite the fact that maximum pacing rate was much higher postop than angina rate preop. Preoperation during pacing, G %L was abnormal in 15 of 18 patients and R %L was abnormal in all 5. Postoperation, G %L markedly improved in 14 and R %L reverted to normal in all 5. Decreased A-V0 2 and higher Po2. both R and G, despite higher pacing stress, together with reversal of abnormal lactate metabolism, suggest improved coronary reserve and indicate that ACB can improve R and G metabolic dysfunction from myocard ial hypoxia in patients with coronary artery disease. These metabolic changes correlate with regional improvement in mechanical function as well.

Pulmonary Fibrosis Due to Tracheobronchial Aspiration : A Prospective Study of the Frequency of Hiatal Hernia and Gastroesophageal Reflux in Interstitial Pulmonary Fibrosis of Obscure Etiology. Edward E. Mays; James ]. DuBois; George B. Hamilton Tracheobronchial aspiration of gastric secretions has been suggested in published reports as a possible cause for idiopathic pulmonary fibrosis. Forty-eight of 131 patients with roentgenographic evidence of pulmonary fi. brosis had no established etiologic diagnosis after individualized evaluations. They were prospectively studied by upper gastrointestinal series to determine the incidence of gastroesophageal reflux . The incidences of both hiatal hernia and reflux were statistically higher in the study group than in (I) a group of 270 age-matched controls who had upper gastrointestinal series for the usual indications, (2) a subgroup of 23 patients with pulmonary fibrosis of established etiology, and , (3) a subgroup of 15 patients who had pulmonary fibrosis and serologic evidence which suggested immune-mediated diseases. The patients in the study group could be further characterized by clinical and roentgenographic presentations, low maximum mid-expiratory How rates, and lung biopsies compatible with interstitial fibrosis. These observations and other cited evidence are supportive of the concept that repeated, small tracheobrond1ial aspirations of gastric acid secretions over a long period of time may cause interstitial pulmonary fibrosis.

A New Method for Monitoring Serum Theophylline Levels to Guide Intravenous Aminophylline Therapy. Richard A . Matthay; Miles M. Weinberger; David C. Levin; Charles A . Chidsey; Thomas L. Petty

Atrial Septal Defect: Ten-Year Surgical Experience in a University Center.]. I . Miller; A . B . Sams; C. R . Hatcher, Jr.

Both the effectiveness and toxicity of theophylline are related to serum theophylline concentration (STC) . Levels < IO.ugf ml are likely to be ineffective while STCs > 20.ugf ml expose patients to the risk of serious toxicity. A rapid, specific, high-pressure ion-exchange chromatographic assay was utilized to monitor STC in adults treated with intravenous aminophylline. Twenty-three patients (ages 20-76) were studied, 19 with obstructive airways disease and 4 with left heart failure. Eleven of the 23 patients had received theophylline prior to the initial STC determination and their levels ranged from 2.5 to 37.5.ugj ml. Five patients with an initial STC < IO.ug / ml received a loading dose of aminophylline calculated to raise STC to IO.ugj ml assuming a mean volume of distribution of 0.5 Lfkg. Thirty minutes after the aminophylline load, the levels were between 10 and 20.ugj ml in 4 patients and 25.5.ug/ ml in one. Fifteen patients received continuous IV aminophylline infusions at the recommended rate of 0.9 mgjkg j hr or less. This resulted in a STC > 24.ugfml in 5 patients, 4 of whom developed symptoms of theophylline toxicity (headache, nausea and vomiting) . The average theophylline clearance for these patients was 0.64 mlfkg j min (range, 0.21.76 ml f kgf min) , approximately one-half the previously reported value. These data suggest that STC should be monitored when administering IV aminophylline because of the unpredictability of initial STC resulting from prior therapy and a high degree of variability in theophylline clearance rates.

From January I, 1964 through December 31, 1974, 207 patients underwent repair of an atrial septal defect at Emory University Hospital. The age range was from 2 months to 65 years with a mean age of 17.5 years. Sixtytwo of 207 patients were older than 30 years of age, and 32 of these were more than 40 years of age. There were 64 males and 143 females. The types of defect were as follows : secundum defects in 168 patients. 23 having associated conditions; sinus venosus defects in 20 patients, 17 with partial anomalous pulmonary venous drainage; ostium primum defects in 12 patients, 10 with an associated deft mitral valve; and a common atrioventricular canal in I patient. Symptoms were present in 140 pa· tients ; 67 patients were asymptomatic. All patients were repaired utilizing cardiopulmonary bypass. Fifty defects required synthetic patch repair and 157 defects were closed primarily. Forty-nine complications occurred in 207 patients with some patients having multiple complications. Hospital mortality was 4 of 207 patients (1.9 percent) . There was no late mortality. Follow-up was obtained in 190 of the 207 cases. The patients have been followed from 6 months to 10 years with a mean followup of 4.3 years. This group of patients represents the wide spectrum of atrial septal defect as seen in a university center during a ten-year period. The symptoms, pathology, surgical repair, and complications of this group will be discussed . Particular emphasis will be placed on the adult patient with atrial septal defect.

420 41ST ANNUAL SCIENTIFIC ASSEMBLY

CHEST, 68: 3, SEPTEMBER, 1975

Risks of Alkalosis in Critically Ill Patients and Their Relationship to Ventricular Arrhythmias. Sherif Mokhtar; Max Harry Weil ; Herbert Shubin

Familial Blunting of Chemoreceptor Activity. Gerald C. Moore; Clifford W . Zwillich; jane Battaglia; Ernest K. Cotton ; john V. Weil

Clinical experience in the management of critically ill patients suggested to us that alkalemia may be a prognostically more unfavorable metabolic state than acidemia of moderate severity. For purposes of objective documentation, a total of 2,453 consecutive blood gas measurements obtained from 299 critically ill patients were reviewed. A majority (69.89 percent) of patients had alkalemia on at least one occasion during the hospital course. However, mortality increased with increasing blood pH , particularly in patients in whom the critical illness was associated with myocardial disease. In view of previously demonstrated relationships between alkalemia and ventricular arrhythmias, this association was examined separately in patients with cardiac disease. In each instance, continuous electrocardiographic monitoring with documentation of rhythm abnormalities was available. Incidence of ventricular arrhythmias increased in close relationship to increasing arterial blood pH with 65 percent of episodes associated with alkalemia. These observations provide evidence of the high risk of alkalemia in critically ill patients and particularly in patients with underlying heart disease. Since alkalemia substantially increases the incidence of epinephrine-induced ventricular arrhythmias, similar mechanisms are most likely involved in critically ill patients in whom alkalemia accounts for increased incidence of ventricular arrhythmia and fatal outcome.

It is not clear whether heredity plays a role in ventila· tory response to hypoxia and hypercapnia . Accordingly, hypoxic ventilatory drive (HVD) and hypercapnic ven· tilatory drive (HCVD) were measured in the parents and all of the siblings of a 10-year-old, previously normal obese boy who suffered acute respiratory failure (Pa02 = 26 mm Hg; PaC0 2 = 53 mm Hg) in the face of a mild lower respiratory illness. He was an otherwise active child, alert and a good student. Neurologic examination , ECG and hematocrit were normal. Arterial hypoxemia and hypercapnia were easily normalized by voluntary hyperventilation. HVD, measured as the shape parameter "A," was 4.0 in the patient (normal = 127 ± 8.7) . In six healthy family members (4M , 2F) whose ages ranged from 15 to 42 years and who had no history of lung disease, HVD was consistently reduced, averaging A = 45 ± 8.7 (P
Experimental Auxiliary Heart Transplantation. Charles H. Moore; Aroind P. Chaukar; Derek Ray; Donald N. Ross

Postoperative Balloon Counterpulsation: Early and Late Salvage. john M . Moran ; Sarah johnson; Henry j . Sullivan; Patrick j. Scanlon; john B. O'Connell; Roque Pifarre

Experimental auxiliary heart transplantation was performed in 35 dogs. The two left atria were anastomosed and the ascending aorta of the transplant (H2) was anastomosed to the descending aorta of the recipient (H · I) . Coronary sinus blood was diverted into the left atrium via the pulmonary artery, and the right heart circulation excluded. Physiologic measurements included ECG, systemk atrial and ventricular pressures, and flow in the aorta of both hearts. In group I (12 animals), there were 8 survivors from 2 to 8 days. Immunosuppressants were not used and only one animal (7 days) died of rejection. The two hearts beat asynchronously but at similar rates. It was possible to pace the hearts synchronously. The transplant H2 did little or no work as determined by pressure pulse contours and flow determinations. In group 2 (23 animals), there were 16 dogs that survived transplantation and subsequent cardiac injury to the recipient HI. As left atrial and LVEDP rose in the recipient, the work load shifted to the transplant H2 resulting in an increase in cardiac output of the allograft. Subsequent exclusion of the allograft resulted in profound shock but was reversible on resumption of flow through H2 confirming the ability of the allograft to support the failing left ventricle. Further studies in controlled asynchronous pacing of the two hearts so that presystolic unloading and diastolic augmentation of the failing HI occurs will be discussed.

CHEST, 68: 3, SEPTEMBER, 1975

In a 2-year period, 35 of 735 patients (4.8 percent) undergoing open heart surgery required intra-aortic balloon counterpulsation (IABC) for drug-refractory op· erative or early postoperative low cardiac output syn· drome (LCOS) . Thirty-two patients had I or more bypass grafts, 4 with associated valve replacement, 7 with aneurysm resection (VAR) , and 1 with VSD repair. Two had VAR without bypass, one with additional VSD repair, and I had replacement of a thrombosed aortic valve prosthesis. All but I patient had apparent cause of LCOS. Seven patients had acute myocardial infarction (AMI) within 6 weeks preoperatively (20 percent) , 12 others had perioperative AMI (34 percent), and another patient had the thrombosed valve. Of the remaining 15 patients, 8 had preoperative congestive failure and 6 had significant LV dysfunction, 2 with aneurysms. -In only I patient was LCOS unexplainable, though he had main left coronary disease. Four patients (II percent) died in the operating room, and 5 others (14 percent) within the first 24 hours. Three were weaned from IABC, but later died in LCOS. Seven· teen patients (49 percent) survived hospitalization. With 4-27 months' follow-up (mean 14 mo) all 17 are alive, 8 in class I, 7 in class 2, and 2 in class 3. Four have angina, 2 have controlled congestive heart failure, and I had reoperation for post-MI mitral regurgitation .

41ST ANNUAL SCIENTIFIC ASSEMBLY 421

It is concluded that drug-refractory postoperative LCOS usually occurs in the setting of pre-existing LV dysfunction or perioperative AM I. !ABC significantly reduces operating room and hospital mortality, resulting in 49 percent long-term survival of good quality.

Physiologic Effects of Bilateral Pneumonectomy with Respiratory Support by a Pumpless Membrane Oxygenator.]. D. Mortensen; Bruce D. Ward Bilateral pneumonectomy has been carried out successfully in ten anesthetized, heparinized 14- to 20-kg dogs in which respiratory function was maintained by means of three parallel 3-sq m Lande-Edwards membrane oxygenators attached by cannulae placed in the proximal pulmonary artery and the left atrial appendage. Each animal achieved physiologic stability for at least one hour, as indicated by essentially normal (prepneumonectomy) values for heart rate, electrocardiogram, cardiac output, central venous and central aortic pressures, right ventricular end-diastolic pressure, blood gases and pH, serum electrolytes, body temperature, and urinary output. Right ventricular systolic pressure increased approximately 30 ± 15 torr, although resistance to blood flow through the prosthetic lung circuit, including cannulae, was less than 10 torr j liter j min. In spite of these relatively normal physiologic parameters, the experimental preparation proved to be unstable with time. There were sudden, unexplained rather dramatic changes in cardiovascular hemodynamics, including cardiac output, systemic arterial pressure, peripheral resistance and circulating blood volume. Respiratory rate and depth of respiratory efforts varied considerably, not always in conformity to blood gases or depth of anesthesia. These animals with total prosthetic lungs were prone to right heart failure, often without good explanation. Sometimes the failing right ventricle would spontaneously compensate; at other times it was refractory to all attempts at management. The longest survival achieved in this lungless preparation was 13 hours. Current studies are underway evaluating the neurovascular, hemodynamic, enzyme, and chemical alterations which auend removal of all lung tissue from the living, otherwise intact experimental animal and efforts are underway to prevent or overcome the right heart failure associated with this preparation. The Oxyhemoglobin Dissociation Curve in Type A and Type B COPD. Evere/J Murphy; Roger C. Bone; Dennis A. Diederich: William E. Ruth Patients with chronic obstructive pulmonary disease (COJ>D) are currently classified in terms of their clinical appearance, ie, type A COPD or "pink puffers," and type B COJ>D or "blue bloaters," with inferences made concerning their course of illness and prognosis. The position of the oxyhemoglobin dissociation curve might be expected to be different in the two groups of patients as a compensation for the different hemoglobin concentrations, arterial oxygen tensions (Pa02), and cardiac outputs. Corticosteroid administration has been reponed to produce a right·shifted oxyhemoglobin dissociation curve in vitro and acutely in vivo. Possibily one beneficial effect of corticosteroid administration in COJ>D may be increased oxygen availability at the tissue level due to a

422 41ST ANNUAL SCIENTIFIC ASSEMBLY

right-shifted oxyhemoglobin dissociation curve. Our purpose was to compare the classical clinical categorization of patients with severe COPD to red blood fell oxygen transport, to compare red blood cell oxygen transport in patients treated with corticosteroids to those not treated with corticosteroids, and to compare red blood cell oxygen transport to chronic hypoxemia and stable pulmonary functions. Twenty-five patients were selected with I) compensated respiratory status, 2) forced expiratory volume (FEV 1 ) ~ 1.5 liter, 3) clinical category in terms of Burrow's classical description of COPD. Type A and type B COJ>D cannot be categorized in terms of red blood cell oxygen transport as measured by Pw 2,3-diphosphoglycerate (2,3-DI'G). and ATJ>. 2.3DPG and ATP are inversely correlated with hemoglobin in type A COJ>D (J><.05) . There is no correlation between levels of hemoglobin and Pr.o. 2,3-DPG, and :\ TP in patients with type B COPD. There is no wrrelation between chronic corticosteroid administration and the position of the oxyhemoglobin dissociation curve in patients with severe COPD. Pulmonary function and blood gases were not independently correlated with Pr.o. 2.3DPG, and ATP. Myocardial Revascularization and Carotid Endarterec· tomy-A Combined Approach?]. Edward Okies: QuentiTI MacManus; Albert Starr Twenty-seven of 1,576 patients (2 percent) undergoing aortocoronary saphenous vein bypass (myocardial re· vascularization) procedures between January 1969 and January 1975 had carotid endarterectomy as well. All patients but one with bilateral asymptomatic bruits had both coronary as well as cerebral symptoms. Three groups of patients were defined (2 patients in group 2 and I patient in group 3 were in other groups as well) : group 1-15 patients having carotid endarterectomy followed by myocardial revascularization; group 2-9 patients having myocardial revascularization followed by carotid endarterectomy; group 3-6 patients having simultaneous carotid endarterectomy and myocardial revascularization procedures. There was I early death (cardiogenic shock) and I late death (bronchopneumonia) in group I following the second procedure, one late death (arrhythmia) in group 2 following the second procedure and no deaths in group 3. There were 5 myocardial complications in group I (2 arrhythmias, I acute coronary insufficiency, I acute myocardial infarction, and I hypotensive episode) following the carotid endarterectomy, I pern1anent cerebral complication following myocardial revascularization in group 2, and I transient and I permanent cerebral complication but no cardiac complications in group 3. Patients with severe stenoses of the carotid and of the coronary arteries should be considered for simultaneous procedures to avoid the serious risks of cerebral or myocardial complications encountered when one or the other procedure is performed first. Mitral Valve Reconstruction: Hemodynamic Evaluation of the Carpentier Ring. james H . Oury; W . W . Angell; T . L. Folkerth; R . G. Fosburg Prosthetic mitral valve replacement carries with it the risk of valve deterioration and failure of the prosthesis. systemic embolization and a higher incidence of infection.

CHEST, 68: 3, SEPTEMBER, 1975

The search for an alternative to valve replacement is therefore warranted and the results subjected to critical hemodynamic evaluation. Forty-one patients underwent mitral valve reconstruction using the Carpentier ring, a prosthetic device which serves as a framework for annuloplasty and valve reconstruction. Twenty-two patients underwent a combined cardiac procedure (coronary artery bypass, valve replacement, etc). Follow-up clinical evaluation is available on all surviving patients. There were two deaths in the overall series (5 percent). Clinical improvement has been documented in 35 patients (86 percent). Complete hemodynamic evaluation including right and left heart catheteri1~tions were performed on 14 patients in this group. The results of this hemodynamic evaluation indicate that the majority (86 percent) of patients undergoing reconstruction for valvular lesions with predominant regurgitation had satisfactory results. Patients with mixed stenosis and insufficiency secondary to rheumatic valvular disease were mainly grouped in the second category. Clinical evaluation of the remaining 27 patients in this series supports the conclusion drawn from the subgroup undergoing postoperative catheterization. We conclude that the Carpentier ring method of annuloplasty provides a valuable adjunct in the surgical treatment of selected groups of patients when the predominant lesion is mitral regurgitation. The results are reproducible and a perfect hemodynamic repair can be effected. The indications for its use in patients with mixed lesions secondary to rheumatic disease are less clear and require careful intraoperative evaluation in each individual case. Respiratory Disease Prevalence in Beauticians and Its Relationship to Aerosol Sprays. Alan Palmer A comparative survey of female cosmetologists practicing in Utah was undertaken to determine if this special subgroup of the population was at increased risk of developing pulmonary dysfunction. This survey was prompted by a plethora of case reports indicating that subjects exposed to aerosol hairsprays became ill with a disease known as pulmonary thesaurosis. A probability sample of 262 student cosmetologists and 213 graduate cosmetologists from all regions of Utah were medically tested and compared to a nonoccupationally exposed control group of 569 people matched by age, smoking history, and region. The medical tests consisted of posteroanterior and lateral chest x-ray films, the forced expiratory spirogram pulmonary test, and a medical questionnaire (Bl\IRC) which included questions on respiratory disease symptomatology, occupational history, smoking history, and aerosol use. Additionally, a subsample received three other tests of respiratory function: sputum, closing volume, and a singlebreath carbon monoxide diffusion test. The major disease categories sought were symptoms of sarcoidosis (this disease is indistinguishable from thesaurosis), chronic respiratory disease (obstructive and restrictive), and abnormal lung cell patholo~ory. Findings demonstrated an increased prevalence of the thesaurosis syndrome when beauticians were compared to the controb, and aho an increased prevalence in beauticians of abnormal lung cell pathology and symptoms of early chroni<· respiratory disease.

CHEST, 68: 3, SEPTEMBER, 1975

Recovery of Alveolar Macrophages from Lung Washings: A Stereologic Evaluation. R. Parad; G. Huber; H. Schauffler; G. Korman; W. Taffe/; C. McCarthy; M. Hayashi; R. Laguarda With the advent of fiberoptic bronchoscopy. segmental brondwpulmonary lavage has proved useful for recovering pulmonary alveolar macrophages. Analysis of these cells is indicated in infections of obscure and undetermined etiology, in evaluating the course of interstitial fibrosis and in the diagnosis of many pulmonary disorders. To date, no critical study exists to determine optimum methods of cell harvest. To study this problem, experimental lavage was performed with isotonic saline and balanced solutions at refrigerated (4• C), room (23• C) and body (37• C) temperatures. Stereology, a science introduced over a century ago by Delesse and adapted to the lung recently by Weibel, was used to quantitatively compare by electron microscopy cells harvested in different ways. Isotonic saline solution proved the lavage agent of choice for optimal recovery of cells. All macrophages from each sample were photographed sequentially and were morphometrically analyzed usii1g a coherent double-lattice test system. Volume densities were determined for 8 cellular components: nucleus. mitochondria, vacuoles, intracellular bacteria, bacterial vacuole space, large and small pleomorphic inclusiom and cell membrane. An analysis of these volume densities showed that the macrophage undergoes significant ultrastructural changes when actively phagocytosing bacteria in situ. Recoverable macrophages differed structurally from the resting in .situ macrophages only in density in the vacuolar and cell-membrane cellular components. Recoverable macrophages contained a larger percentage of vacuoles and had a smaller cell surface, both presumably secondary to lavage with saline. Volume densities for all other mmponents did not differ significantly. thus indicating that the alveolar macrophage recoverable from the lung by lavage with isotonic saline is ultrastructurally the same cell as the resting in situ alveolar macrophage.

Effect of Experimental Prophylactic and Therapeutic Steroid Administration on the Course of Oxygen Toxicity. IV. Pereira ; F. Carr; H. Bene.w va; G. Huber Administration of high concentrations of 0~ is essential to most patients with respiratory failure. Frequently, corticosteroids are simultaneously employed in the management of many diseases that cause respiratory failure. The effect of steroids on the course of 0~ toxicity is controversial, and may be affected by the specific time at which steroid therapy is initiated. To study this problem, high dosage (50 mgjkg) and low dosage (5 mgjkg) methylprednisolone succinate therapy given every 12 hours was initiated in mice prophylactically before or therapeutically at 72 hours of exposure to 100 percent 0~ over an accumulative 120 hours of continuous 0 2 exposure. The response of the lung to 0~ alone, steroids alone or both was evaluated by quantification of lung injury by wet-dry lung weights and parenchymal histology. Nonsteroid 0 2 -exposed animals developed pulmonary edema, alveolar hemorrhage and hyaline membranes with an average mortality of less than 10 percent after 120 hours of 0 2 exposure. Both prophylactic and therapeutic steroid administration significantly enhanced

41ST ANNUAL SCIENTIFIC ASSEMBLY 423

the severity and accentuated the course of pulmonary oxygen toxicity. quantified by wet-dry lung weights and lung histology and increased by approximately threefold the mortality. These results demonstrate that the host is more susceptible to the toxic manifestations of 02 when steroids are simultaneously administered and that steroid treatment in acute 0 2 toxicity enhances rather than diminishes its course. The clinical implication of these studies is that steroid therapy should be avoided, if possible, when high concentrations of 0 2 are used in the management of respiratory failure. Comparison of Right and Left Heart Catheterization in Assessing Prognosis in Acute Myocardial Infarction. ]. Price; Ezra A . Amsterdam; A. N . DeMaria; R . R .Miller; Dean T . Mason Accurate assessment of prognosis in acute myocardial infarction (AMI) is essential for appropriate, early application of new approaches to management of cardiac pump dysfunction in AMI. Therefore, the comparative value of right (R) and left (L) heart (H) catheterization (C) in evaluating prognosis in AMI was analyzed. RHC was performed in 238 patients and LHC in 34 patients within 48 hours of admission. Prognosis was assessed in relation to the following factors: arterial pressure (P). peripheral vascular resistance, right atrial P, pulmonary artery P. pulmonary wedge (PW) P. cardiac index, cardiac work index (CWI) , stroke work index (SWI) , SWi f PWP. L ventricular (V) end-diastolic (ED) P, SWi f LVEDP, peak LV dP fdt, and peak measured LV contractile element velocity. Separation of survivors (S) and nonsurvivors (NS) was best with CWI , SWI. SWI f PWP and SWi f LVEDP. RHC : CWI >0.7 kg-MfM2-+ 92.7 percent (202/218) Sand ~0.7 -+95.0 percent (19/ 20) NS; SWI > 11.0 gm-MfM2-+ 96.6 percent (200/207) S and ~ 11.0 -+90.3 percent (28 / 31) NS; SWifPWP >0.5 -+97.6 percent (200 / 205) S and ~0. 5 -+90.0 percent (30 / 33) NS. LHC : CWI ~ 1.5 kg-M j l\f2 -+ 100 percent (15 f l5) Sand <1.5-+ 86 percent (12 / 14) NS; SWI ~ 12 gm-MfJ\12-+ 93 percent (13 / 14) Sand <12 -+ 79 percent (ll f l4) NS; SWi f LVEDP ~0. 86-+ 93 percent (14 / 15) Sand <0.86-+ 92 percent (11/12) NS. Both RHC and LHC were highly accurate in separating Sand NS in AMI. LHC provided no advantage over RHC. Therefore, RHC provides important prognostic information regarding risk of mortality related to cardiac pump dysfunction in the early phase of AMI. This approach can be readily applied and a llows rational selection of current therapeutic modalities. Open Lung Biopsy in Acute Diffuse Pulmonary Disease. R . M . Quinlan ; H . Laks; Lawrence H . Cohn; john ]. Collins, Jr. Acute diffuse pulmonary disease presents a serious therapeutic dilemma, particularly in patients in whom body defense mechanisms are depressed. Open lung biopsy has been performed so that unnecessary "shotgun" treatment with highly toxic agents might be avoided in critically ill patients. Between 1970 and 1975, 53 open lung biopsies were performed on 50 patients ranging in age from 15-74 years (mean 43) classified in 4 categories, rheumatoid patients on immunosuppression (7), renal transplant recipients (7), lymphoma patients on chemotherapy (17) and primary

424 41ST ANNUAL SCIENTIFIC ASSEMBLY

pulmonary pa thology (19) . A specific diagnosis was made in 30 / 53 biopsies (57 percent); the remaining 23 were nonspecific interstitial pneumonitis. There were 16 postoperative ( < 30 days) deaths (32 percent) and 10 nonfatal compli<:ations (18 percent) ; no death could be directly related to the procedure per se. Biopsy was helpful in delineating specific therapy or avoiding unnecessary toxic therapy in 40 patients (80 percent). but ultimate survival was effected in only 27 patients (58 percent) . Biopsy was done in 7 patients in whom percutaneous needle biopsy had failed to delineate a specific diagnosis. Our experience suggests that open lung biopsy is helpful in delineating a specific diagnosis, contributes significantly to avoiding unnecessary therapy. but does not appea r to markedly alter the ultimate course of patients with diffuse pulmonary disease. Left Ventricular Assist Device to Support the Failing Heart: An Experimental Study. IV. Grrald Rainer; Theodore R. Sadler, Jr. ; McClellan G. Blair; Paul Spehr~ Philip Litwak In order to provide optimal support, assistance for the failing heart must reduce the pre-load on the left ventricle (LV) . Blood return is preferably during diastole to provide maximal coronary perfusion . A device providing this support conceivably can be applied to those patients with "pump failure " whose hearts might reasonably be expected to recover functionally within days or weeks. We present our experience with such a device, the abdominal left ventricular assist device (ALV AD) . model

7.

ALV AD consists of a pneumatically driven , EGG-synchronized system which occupies a left subdiaphragmatic position, with transdiaphragmatic inAow tube into LV. and outAow Dacron prosthesis sutured into the infrarenal aorta. The elastomeric pumping ventricle has a 140-ml capacity and an ejection fraction variable up to 70 percent. The inner surface of the entire system provides a Dacron-Aocked interface for blood (Dacron fibrils 25~ X 250~ ; 45,000 f in2) Caged-disk valves allow for unidirectional How. Output of 10 L f min can easily be achieved . An external control unit provides power, time and va riable-delay synchronization. To date, ALVAD units have been implanted into 8 calves (40 to 85 kg) . After continuous pumping for 2 weeks in one animal, the ALVAD was removed and this animal is alive and thriving 3 months later. Parameters measured to assess tolerance and effect on organ function include: arterial, venous, left atrial and LV pressures, routine blood and coagulation studies, liver and kidney function values, and RBC fragility indices. Thus far, the ALVAD model 7 appears to be well tolerated, to support organ function adequately, and to take over cardiac function in a near-total fashion, thus safely allowing ample time for reversible healing of the heart to take place. Removal of the ALVAD after an appropriate interval appears feasible and clinically applicable. Responses of Patients with Asthma to Aerosolized Isoproterenol Inhaled at Different Lung Volumes. IJ. ]. Riley; B. W eitz; N.H. Edelman Patients usually inhale aerosol bronchodilators at low lung volumes, but better distribution of drug may occur

CHEST, 68: 3, SEPTEMBER, 1975

if inhaled near TLC since airways tend to be more widely patent. To test this, we compared the bronchodilator response to aerosolized isoproterenol at high and low lung volumes in 13 asthmatic subjects. We used half the sta ndard dose of isoproterenol (0.04 mg) to be closer to the more sensitive region of the doseresponse relationship. The aerosol was inhaled from a Freon cartridge at either 20 percent or 80 percent of the inspired vital capacity using an apparatus designed to produce a constant inspiratory flow rate and allow continuous measurement of inspired volume. The tests were done on separate mornings and the control measurements of FEV 1 were within 15 percent of each other. Measurements of FEV 1 and specific conductance (SGaw) were made before and 10, 20, 30, 45, 60, 90, 120 and 150 minutes after inhalation. At 10 minutes, there was a significantly greater (average : 25 percent; P < .05) improvement in FEV1 when the drug was inhaled at 80 percent as compared to 20 percent of vital capacity. There was no difference in effectiveness after 10 minutes. The degree of improvement in SGaw was not significantly different using the two methods of administration. We conclude that a greater bronchodilator effect occurs when equal doses of drug are inhaled at 80 percent as compared to 20 percent of the vital capacity. This may be due to greater delivery of drug to more distal airways in general or to improved distribution of the drug to the most constricted airways at the higher lung volume. It may be useful to train asthmatics to inhale bronchodilators at high lung volumes. Vocal Cord Injection for Respiratory Failure after Recurrent Nerve Section. Michael Rontal; Eugene Rontal; Stewart Pursel The loss of the cough reflex is the most serious immediate complication of recurrent laryngeal nerve section. Without the glottis to produce an effective cough, a patient may progress to respiratory failure from inability to clear his own secretions and from atelectasis. Usually, treatment is symptomatic, and the only means available are transnasal and transtracheal suctioning, bronchoscopy. tracheostomy, endotracheal intubation and inhalation therapy. The restoration of glottic function after the loss of the recurrent laryngeal nerve is the key to the most efficient treatment. This can be accomplished by the injection of Teflon into the paralyzed vocal cord. This is a simple, atraumatic, and safe procedure. It is prophylactic if the loss of the recurrent nerve is discovered early or known at surgery. and is corrected if aspiration has already occurred. A series of 30 patients with acute loss of recurrent nerve who have been treated with this procedure are presented. By using subglottic pressure measurements along with their clinical course, it can be objectively seen that these patients had a dramatic improvement, second ary to the laryngeal injection. The results were immediately effective and proved useful on a chronic basis. It is efficacious and should be a prominent part of the armamentarium for the care of recurring aspiration that accompanies a surgical or pathologic section of the recurrent nerve.

CHEST, 68: 3, SEPTEMBER, 1975

The Role of Bronchofiberoscopy with Saline Lavage in the Treatment of Respiratory Failure. james M . Schibano[J; Anthony j . Cuomo The removal of retained secretions from the lung is an important part of the therapeutic effort during acute respiratory failure in chronic lung disease. Bronchofiberoscopy provides a new, safe method of managing retained secretions. Nine cases of severe respiratory fa ilure requiring intubation and assisted ventilation occurring in patients with advanced chronic lung disease were treated conventionally, as well as with early bronchofiberoscopy with saline lavage. Bronchoscopy with saline lavage was carried out as soon as feasible during assisted ventilation , and resulted in successful extubation in all cases within two hours (1.6 hr ± 2.4 hr) of the procedure without tedious wean ing. The mean assisted ventilation time for the series was 17.7 ± 12.5 hours (±SD) . The saline lavage volume averaged 355 ± 184 mi. !\lor· tality from pulmonary embolism occurred in one patient 48 hours after extubation. Mean hospital stay for the remaining patients was 8.9 ± 4.0 days. In chronic lung disease, effective removal of retained secretions by early intervention with bronchofiberoscopy and saline lavage may significantly shorten the course of acute respiratory failure. Radiographic and Hemodynamic Comparison of Pulmonary Hypertension in Severe Chronic Airways Obstruction. Marvin I. Schwarz; james H . Ellis, jr.; Richard A. Matthay; john R . Durrance; Paul E. Siebert; David C. Levin The criteria for the radiographic diagnosis of pulmo· nary hypertension (PHT) in severe chronic airways ob· struction (SCAO) have not been established. The purpose of this study was to compare chest radiographs with catheterization data in SCAO and to compare the radiographic find ings with normals. Fifty-two men (average age 60) with stable but SCAO (FVC, 2.7 ± 0.14 L; mean ± SEM; FEV 1 o, 1.07 ± 0.07 L) underwent right heart catheterization. Mean pulmonary artery (PA) pressure was 30 ± 1.5 mm Hg (range 15 to 61) ; 6 had normal pressure (PA ~ 20 mm Hg) . Their chest radiographs and those of 46 normals were independently evaluated by 3 observers. The following observations and measurements were made: presence of vascular attenuation; diameter of the right (R) and left (L) PA ; estimation of main PA size; and cardiac size. The accepted maximum normal size of the RPA was 16 mm while that of the LPA was found to be 19 mm (15 ± 2 mm ; mean ± SD, present study) . In the normals, all parameters were within normal range. In SCAO the presence of vascular attenuation (50 of 52), main PA enlargement (34 of 52) and cardiomegaly (I of 52) helped predict PHT (PA pressure > 20 mm Hg) , but correlated poorly with the severity of the PHT. Using the RPA > 16 mm as an indicator of PHT, there were 3 false negatives and 2 false positives. Using the LPA > 19 mm as a sign of PHT, there were 3 false negatives and 4 false positives. However, there were no false negatives when either the R or LPA was enlarged. Neither the diameter of the R nor LPA correlated well with the level of PA pressure (r 0.41 and 0.36 respectively) . Data suggest that the subjective and objective evaluation of the chest radiograph in SCAO can predict the presence but not the severity of PHT.

=

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Status Asthmaticus Requiring Assisted Ventilation. Charles H . Scoggin; Steven A. Sahn; S. Lakshminarayan A retrospective analysis of status asthmaticus leading to assisted ventilation was undertaken. All patients admitted to Colorado General Hospital from 1967 to 1975 with status asthmaticus requiring mechanical ventilation were studied. Eighteen episodes of assisted ventilation occurred in 17 patients. There were three males and 14 females ranging in age from 16 to 67 years (mean 39 years). The precipitating causes leading to status asthmaticus were respiratory infection in eight, bronchoscopy in two, trauma in one, discontinuation of medicatiou in one, and were not readily discernible in six instan<·es. There was wide variation in the duration of status asthmaticus prior to the institution of ventilatory assistance. The duration of assisted ventilation ranged from two hours to 25 days. Thirty-seven major complications were observed in 14 episodes. Pneumonia and pneumothorax occurred most frequently and were associated with an increased mortality. The meari survival rate of the entire group was 52.6 percent. The mean age of the survivors was 38.7 years while that of the nonsurvivors was 44 .5 years. The mean duration of assisted ventilation was 3.9 days in the survivors and 5.9 days in the nonsurvivors. The clinical implications of these data will be discussed. Sequential Intraoperative Arterial Blood Gas Monitoring during Thoracic Surgery: Its Value in the Recognition and Treatment of Unsuspected Acute Respiratory Failure. Nathan S. Saiff; Michael McPeck; Lewis Levin; Robat Lord; julius IV. Ga111ey The suspicion that several thoracic surgical intraoperative problems, including mortality, might have been due to undiagnosed acute respiratory failure, led us to study prospectively the arterial blood gas levels in 30 consecutive patients undergoing thoracotomy for pulmonary surgery. Measurements were obtained from a radial artery line before and during induction of anesthesia, and approximately every half hour thereafter until the patient left the recovery room. In the first 15 patients, acute respiratory failure. as judged by one or more PaC0 2 readings of above 50 torr. was present in 8 (53 percent) . In 3 patients. PaCO:! above 70 torr was recorded. In one patient , the 1'aC02 went as high as 130 torr, with a fall of the pH to 6.99. In all of these patients the anesthesiologist was unaware clinically of the existence of any problem. After being informed of the elevated l'aC02. it was normalized within a short time by airway care and mechanical ventilation, and fortunately there were no complications or mortality. In the second 15 cases, the PaC0 2 was elevated in only 4 patients (26 percent) . In addition, the degree of hypercapnia was also significantly lower. As the anesthesiologists began to increasingly follow the blood gas results in patient management, the hazard of significant acute respiratory failure ceased, and prompt management was applied to even slight elevations of the PaC02. It appears, therefore, that the routine use of frequent intraoperative arterial blood gas measurements through an indwelling arterial line is a simple and very worthwhile physiologic parameter to monitor during pulmonary surgery.

426 41ST ANNUAL SCIENTIFIC ASSEMBLY

Limitations of ECG and Vectorcardiography in Detecting Subendocardial Necrosis in Aortocoronary Vein Bypass Grafts. Harjat Singh; Ro/Jert } . Flemma ; Al{1-erl ] . Tect01·; Roger P. Gabriel; Derward L,~pley, ]r. To determine the significance of elevated enzyme levels postoperatively. 202 consecutive patients undergoing aortocoronary vein bypass grafts had SGOT. LDH. LDH (H), and CPK values determined one day prior to operation and 3rd to 7th day postoperatively. Serial postoperative ECG and \·ectorcardiograms revealed myocardial infarction (MI) in 12 patients. Group I was comprised of 32 patients who had significant elevation of SGOT (> 30 units) and LDH (H) value (> 90 units) postoperatively. Group 2 consisted of 72 patients who had a lower rise in values : SCOT between 20 ami 30 units and LDH (H) values between {iO aud 90 units. Group 3. 98 patients, had normal enzyme values (SGOT, 3 to 20 units : LDH (H), 0 to 60 units) postoperatively. Ouly 8 patients in group I (25 percent) and 4 patients in group 2 (5 percent) could he shown to have sustained MI. Three of the patients died yielding a hospital mortality ol 1.5 percent and l\1 I rate of 6 percent. Significant elevation of isoenzymes without discreet MI occurred in IIi percent of the patients. Significantly. more patients undergoing triple vein bypass, longer cardiopulmonary bypass and endarterectomies belonged to group I and 2 than group 3 (I' < 0.05) . l'reinfarction angina (I' < 0.025) and presence of hypokinesia (P < 0.005) were also higher in group I and 2 patients. Duration of in-hospital stay was similar in the three gmups. Significantly elevated isoenzyme levels without evidence of discreet 1\11 suggests that subendocardial necrosis may be more frequent than is commouly realized in vein bypass procedures. ECG and vectorcardiography were of limited value in this assessment.

BronchodiJa(ing Effects of Aerosolized Sch 1000 and Atropine Sulfate in Asthmatics. Shddon Sputor; Uobnt E. Ball, Jr . Aerosolized Sch 1000, an atropine-like anticholinergic drug, was administered to 15 asthmatic patients in two doses and compared to atropine sulfate to determiue the time of onset. duration and bronchodilator effect. Responses were compared for FEV 1 and FVC with measurements of 15, 30, 60, I20 and 180 minutes. For both parameters. the onset of bronchodilation for 401-'g and 801-'g Sch 1000, as well as atropine sulfate (2 mg) was ~ 15 minutes. There were significant (P<0.05) increases in pulmonary function over baseline for all treatments at all times of measurement. Adverse effects, unrelated to dose. principally mouth and throat dryness, were more common and longer lasting with atropine than with Sch 1000. Some degree of responsiveness was demonstrated in all subjects. However, certain individuals consistently showed minimal bronchodilation with all three test solutions, while others were markedly responsive. Threshold response to aerosolized methacholine and histamine did not predict anticholinergic responsiveness. This suggests heterogeneity of mechanisms in the pathogenesis ol asthma. Long-term treatment with atropine sulfate has been disappointing and may be related to the frequency of usage.

CHEST, 68: 3, SEPTEMBER, 1975

Lmg-Term Clinical Assessment of Bedomethasone Dipropionate and its Effect on the H-P-A Axis after Substitution for Oral Corticosteroids in Chronic Asthma. Shimon A . Spitzer; H. Kaufman; A . Koplovitz; M. Topil· sky; I. Blum Bedomethasone dipropionate (BMD) administered by inhalation has been shown to be effective in the control of bronchial asthma. This study was undertaken to assess its long-term clinical efficacy and concomitantly its effect on the H-P-A axis after substitution for oral corticosteroids in steroid-dependent asthmatics. Thirty patients suffering from chronic perennial asthma of moderate and severe degree were the subjects of this study. Following the administration of BMD, 100 ,ug 4 times daily, 29 showed marked improvement in their symptoms. This was manifested by improvement in their severity and disability scores, improvement in ventilatory function and a marked reduction in the use of bronchodilators. Moreover, in 20 of the 24 steroid-dependent asthmatics who received an average prednisone dose of 7 mg daily for a mean duration of 7.3 years, oral corticosteroid therapy could be withdrawn. Marked steroid withdrawal symptoms appeared in 7 patients, but subsided gradually within 3 months. These were characterized by weakness, muscle and joint aches, hoarseness, weight loss and depression. In 8 patients previous allergic rhinitis recurred. During a one-year follow-up 2 patients had to resume their oral corticosteroid medication. All the others remained improved. Assessment of the H-P-A axis was carried out in all patients before and after I, 3 ·and 6 months of the initiation of BMD therapy. Urinary 17-hydroxycorticosteroids, free urinary cortisol and plasma cortisol were measured before and on the day of a tetracosactrin test. An insulin tolerance test for the assessment of hypothalamic-pituitary function was performed one day later. From the rate of recovery of the H-1'-:\ axis with BMD therapy, it may be assumed that the one-year assessment of the H-P-A axis will demonstrate normal function with no residual endocrine defects.

Comparison of Calcium, Isoproterenol and Norepinephrine on Cardiac Output before and after Orthotopic Prosthetic Heart Replacement. Theodore H. Stanley ; Wen-Shin Liu; judd Lunn; Scott Gentry An ideal experimental animal model for study of the differential cardiovascular effects of drugs with peripheral vascular and direct cardiac effects is the awake, spontaneously breathing calf before and after its natural heart is removed and replaced with a pulsatile artificial heart (AH) . In this study the effects of calcium (Ca++), isoproterenol (I) and norepinephrine (N) on Fick-
CHEST, 68: 3, SEPTEMBER, 1975

given IV and the above parameters immediately remea· sured. The study was repeated 4-36 days after AH implantation when cardiovascular dynamics and CO approximated pre-AH implantation values. Ca++ and I produced 31 and 59 percent increases in CO before :\H implantation and 16 and 25 percent increases after implantation . N produced a 43 percent reduction in CO before and a 54 percent reduction after AH implantation. Ca++ did not change while N significantly raised A, RA and I' A pressures both before and after AH implantation. I reduced A pressures significantly more after AH implantation than before hut had no effect on RA or I' A pressures. These data demonstrate that Ca++, in addition to I and N, has a marked peripheral vascular as well as positive cardiac inotropic effect.

Pulmonary Manifestations of Sjogren's Syndrome. C. Vaughn St1·imlan; E. C. Rosenow , Ill; Matthew fl. IJivertie; Edgar G. Harrison, Jr. The pulmonary changes associated with Sji)gren's syn· drome are not well established and the frequency of pulmonary involvement is very poorly documented. A review of 343 patients seen at the Mayo Clinic from 1967 through 1974 with classic Sjiigren's syndrome revealed pulmonary involvement in 31 patients, an incidence of approximately 9 percent. There were 25 women and 6 men in the series, with a mean age of 56.5 years. When initially seen, five patients were asymptomatic, hut cough, dyspnea, recurrent pneumonitis, and pleuritic pain were the primary complaints of the remaining patients. Chest roentgenographic features were quite vari· able, ranging from diffuse interstitial patterns (fine reticular and fine reticulonodular to coarse reticular and coarse reticulonodular), diffuse acinar patterns, and pleural effusions. Laboratory studies revealed hypergammaglobulinemia in 16 of 22 patients tested. In addi· tion, 16 of 24 patients had a positive antinuclear anti· body, 16 of 29 had a positive rheumatoid factor, and 6 of 27 had a positive LE preparation. Pulmonary function tests showed a restrictive ventilatory impaim1ent andjo1 low diffusion capacity in all 18 patients studied. Pulmonary biopsy or necropsy specimens established the diagnosis in 13 patients. Pathologic diagnosis included the full spectrum of lymphoproliferative disorders de· scribed in Sjiigren's syndrome: lymphocytic interstitial pneumonitis (3 patients, 2 of whom also had amyloi· dosis); pseudolymphoma (I patient); and malignant lymphoma (3 patients) . In addition, 3 patients had dif. fuse interstitial pulmonary fibrosis and 3 had bronchopneumonia. The clinical diagnosis in the remaining 18 patients included: diffuse interstitial fibrosis (II pa· tients) ; recurrent pneumonitis (3 patients) ; pleural effu· sions (2 patients) ; and suspected lymphoma or psetidolymphoma (2 patients) . This is the most extensive review of Sji>gren's syndrome in which an attempt has been made to establish the incidence and define the relationship of pulmonary dis· ease in this entity. Based on these findings and a review of the English literature, a classification of the pulmonary manifestations of Sjiigren's syndrome is presented. It is concluded that pulmonary lesions occur in Sjiigren's syn· drome much more frequently than previously reported.

41ST ANNUAL SCIENTIFIC ASSEMBLY 427

Physiologic Consequences of Severe Unilateral Experimental Emphysema. Timothy Takaro; Gulshan K. Sethi; LeeR. Gaddy

Rapid Diagnosis of Anaerobic Empyema by Direct Gas Chromatography. H. Thadepalli; ]. G. Bartle//; S. L. Gorbach

Severe unilateral emphysema was produced in eight dogs by repeated instillations of the protease, papain, into the right lung, while the left was protected by a tracheal divider. As compared with six controls, FRC of individual lungs, measured simultaneously by dual closedcircuit helium spirometry in prone, supine, and both lateral decubitus positions, showed maximal alterations in the supine and left lateral positions, with increased FRC to three times normal on the right, and diminished FRC to % normal on the left (P < 0.02) . This corresponded to reduced arterial Po~ in these positions. Dynamic compliance of experimental animals was doubled (P < 0.025), and frequency dependence of compliance, indicating small airways obstruction, was observed. Marked asynchrony of the respiratory phases of the two lungs in experimental animals was also noted, with reversal of the normal ratio of duration of inspiration to expiration. The most severe derangements were in the right lateral decubitus position. Hypercarbia was observed in all four positions. This model may be unique, since it embodies two lungs in parallel with radically different volumes, compliances, and time constants. It allows investigation of phenomena difficult to study experimentally, such as asynchrony of diaphragmatic movements, and "pendelluft" between two lungs. The model may help increase understanding of the relationships between ultrastructure (scanning and transmission electron microscopic studies) and function in "pure" pulmonary emphysema.

Anaerobic empyema often requires immediate confirmation of diagnosis. Anaerobes produce short-chain fatty acids, a feature used in their identification. Hence, direct gas-liquid chromatography (GLC) of pleural aspirates was done in 24 patients and cultured for aerobic and anaerobic bacteria. Acid-ether extract of the pleural fluid was injected into a thermoconductivity gas-chromatograph. Eighteen patients who had fungi, mycobacteria or other aerobes or sterile fluid yielded no fatty acid pattern on GLC. Six patients had anaerobic empyema; 3 had only anaerobes and 3 had mixed aerobic f anaerobic bacteria. Direct GLC of empyema fluids in 5 patients revealed propionic, isobutyric, butyric, isovaleric and caproic acids in variable quantities, but the composite pattern was compatible with the basic chromatograms typical of anaerobic bacteria found in the specimen. Anaerobes isolated from these 5 patients were Peptostreptococcus ( Ps) anaerobius , PJ intermt•dius, Peptococcus asaccharolyticus, Bacteroides me/aninogenicus, B fragilis, Fusobacterium, Eubactaium lentum, Lactobacillus cantenaforme and Veillonel/a parvula. The 6th case due to Ps intermedius was falsely negative on GLC because fatty acid production is not a feature of this anaerobe. There were no false positives. Appropriate therapy in 2 patients cleared anaerobes from pleural fluid and the fatty acid pattern disappeared on direct GLC. Direct GLC of pleural aspirate, which can be done in 30 minutes, may be used as an additional diagnostic tool in anaerobic empyema.

Reduction of Blood Usage in Open Heart Surgery. Alfred ]. Tector; Roger P. Gabriel; William E. Mateicka; Sonn)' S. Oparah; Robert ]. Flemma; Derward Lepley,

Value of Transtracheal Aspiration in the Diagnosis of Sputum-Negative Pulmonary Tuberculosis. Haragopal Thadepalli; Albert H. Niden

To reduce blood usage during cardiac surgery, the following protocol was undertaken in 142 consecutive patients undergoing valvular, coronary and congenital procedures. Preoperatively, I to 2 pints of blood were removed from the patient. Total hemodilution, short cardiopulmonary bypass time, careful hemostasis, postoperative diuretics and volume expanders were concomitantly used. The patient's blood was returned to him. A hematocrit value of up to 25 percent during the procedure was aimed for. Using this protocol, 20 patients (14 percent) needed no blood, 27 patients (19 percent) needed no blood during surgery, 49 patients (35 percent) needed no blood in the postoperative period. The average blood requirement for the entire group was 165 units whole blood and 1.14 units of packed cells for the entire hospital stay. Included are 4 patients in the group who bled postoperatively and needed a second operation. The average postoperative blood loss was 825 mlfpatient. Iron therapy was supplemented postoperatively. Follow-up hematocrit values were within normal range. It is evident that postoperative blood loss and blood usage were minimized with no risk to the patient. The potential advantages in cost to the patient and community and minimization of risk of hepatitis and transfusion reactions are underlined.

Seventy-two new cases of pulmonary tuberculosis were detected in our hospital during a 21-month period among approximately 2,625 admissions to the Department of Internal Medicine (27 / thousand adults) . Sputum examination was positive for acid-fast bacilli (AFB) in 51 (70.8 percent) patients with a colony count of 200 to 400f ml. In 21 (29.2 percent) sputum-negative patients (SNP), diagnostic clues were sought by percutaneous transtracheal needle aspiration (TTA) ( 16), lung biopsy (2). pleural aspiration (2), and lymph node biopsy (I). At least 3 sequentially induced sputum specimens, including I on the day of TT A, were negative by smear in all 21 patients and in 16 by culture as well. TTA revealed AFB by smear and culture in 15 of 16 SNPs in a concentration of less than 20 colonies f ml. Following TTA, sputum turned positive in 3. Of 15 positive TTAs, Mycobacterium tubnculosis was the only isolate in 7 patients. The remaining 10 TTAs (75 percent) were associated with other aerobic bacteria in 7 and both aerobic and anaerobic bacteria in 3. They were streptococci (6), staphylococci (4), Pseudomonas (3) , micrococci (2) , lactobacilli (2) and one each of Neisseria, Citrobacter fruendii, diphtheroids, Peptostreptococcus intermedius, Peptococcus constellatus and Actinomyces naeslundii. Six of the I 0 patients with other bacteria in TTA were toxic and required an appropriate antimicrobial in addition to antituberculosis therapy. Four patients did well on antituberculosis ther-

Jr.

428 41ST ANNUAL SCIENTIFIC ASSEMBLY

CHEST, 68: 3, SEPTEMBER, 1975

apy alone. In summary, nearly 30 percent of patients with sequentially negative induced sputa required additional diagnostic procedures, such as TT A, bronchoscopy and biopsy to establish the diagnosis of active pulmonary tuberculosis. TT A alone resulted in positive smears and cultures in 71 percent of SNPs. Sputum might be negative, hut a TT.-\ may reveal AFB in the trachea presumably due to salivary dilution of the sputum or due to supra-infection with aerobic and / or anaerobic bacteria necessitating additional antibiotic therapy. Pseudoaneurysm (False Aneurysm) of the Left Ventricle. Felix E. T,-istani; Vi,-inderjit S. Bamrah; Charles V. Hughes; Robnt ] . Flemma Pseudoaneurysm of the left ventricle is thought to be a rare condition which develops when blood leaks from a perforation in the myocardium and is contained by a fibrinous pericardium. It may occur after ventricular myotomy, sharp or blunt trauma, myocardial infarction or endocarditis. We have observed five patients who developed this entity as a complication of cardiac surgery. In two patients, the pseudoaneurysm occurred after mitral valve replacement and in neither instance was a myotomy performed. In retrospect the pseudoaneurysm was apparent by chest x-ray examination within 24 hours after surgery. One patient underwent surgical correction and the other died suddenly at home. Three other patients developed the pseudoaneurysm at the site of prior aneurysmectomy. Left ventricular failure developed 2-16 months after surgery. One patient died of rupture of the pseudoaneurysm . In the other two patients, the diagnosis was made on clinical grounds and confirmed by ventriculography. Successful repair was accomplished with improvement in ventricular function . Pseudoaneurysm of the left ventricle can be suspected in a patient with one of the above presenting factors on the basis of physical examination and chest x-ray film findings and confirmed by ventriculography. Awareness of this entity with prompt diagnosis and treatment is essential since it may lead to cardiac decompensation and fatal rupture. Aneurysm of the Membranous Septum Associated with Congenital Heart Disease. Bernardo A. Vidne; Luigi Chiariello; julio Agosti; Henry R. Wagner; S. Submmanian Twenty-seven patients with aneurysm of the membranous septum in association with various cardiac abnormalities are described. The preoperative clinical findings, cardiac catheterization data and angiography were studied. The subsequent operative procedure and postoperative course were also reviewed. The patients' ages ranged from 3 months to 17 years. All of the 27 patients were divided into four groups. Group I consisted of 10 patients with ventricular septal defect, group 2 included 5 patients with VSD and an atrial septal defect, group 3 consisted of 5 patients with VSD and pulmonic obstruction and group 4 had 7 patients with transposition of the great arteries and VSD, 3 of them with associated pulmonic obstruction. In all the patients, complete correction was performed and the aneurysm was imbricated in the suture line of the VSD present in all the cases. There was only I hospital mortality due to subpulmonic obstruction in the first patient with aneurysm of the

CHEST, 68: 3, SEPTEMBER, 1975

membranous septum in TGA and VSD in whom the aneurysm was not suspected preoperatively and overlooked at surgery. There was no late death . When these accompanying aneurysms are encountered during surgery or previously diagnosed, resection or imbrication of the sac should be accomplished in order to prevent further enlargement, postoperative arrhythmias and especially in TGA to avoid fatal subpulmonic obstruction as occurred in our only death. The hemodynamic characteristics of this aneurysm in transposition of the great arteries will be discussed specifically.

The Effect of Albumin and Diuretics on the AlveolarArterial Oxygen Gradient in Patients with Pulmonary Insufficiency. Barry Vinom,-; ] . Sheldon Ariz; ]ames E. Sampliner; Elmer]. Perse To better define the role of albumin and diuretics in the treatment of patients with pulmonary insufficiency, we have treated 35 such patients on our surgical intensive care unit with a regimen combining salt-poor albumin and furosemide. Before receiving the treatment combination, 5 of the patients (14 percent) were treated with albumin 8 to 10 hours before they received the combined regimen, and 5 patients (14 percent) were treated with furosemide alone 9 to 12 hours before they received the combined therapy. Each patient had baseline, and one- and two-hour posttreatment measurements of A-aD02 (F102= 1.0) , urine output, Qs / Qt, and arteriovenous oxygen content difference (A-VCD02), and selected patients had cardiac output determined with a thermodilution technique. Serum albumin was measured prior to treatment. Central venous pressure (CVP) was routinely monitored and 23 of 35 (66 percent) patients had pulmonary artery and pulmonary capillary wedge pressures monitored with a SwanGam catheter. After baseline measurements, the treatment was administered. In those patients receiving combined therapy. 25 gm of salt-poor albumin was infused over I to 2 hours; 20 minutes after the albumin had been absorbed , the patients were given 40-60 mg of furosemide intravenously. None of the patients treated with a single modality (ie, furosemide alone or albumin alone) responded with a decrease in A-aD0 2 that represented a statistically significant difference from their control measurement. However, of the patients treated with the combined regimen, 23 of 35 (66 percent) showed improvement, defined as a reduction in the A-aD0 2 of at least 50 mm Hg by the end of the first hour. This group had a mean decrease in A-aD0 2 of 93 mm Hg (SEl\1 ± II) at the end of the first hour. The patients who did not improve had a mean decrease in A-aD02 of 14 mm Hg (SEl\1 ± 4). Mean serum albumin concentrations in the two groups were not significantly different prior to treatment. There was, however, a statistically significant difference in urine output between the two groups following the administration of the combined regimen . The majority of patients who did not respond favorably to the regimen were those patients who developed pulmonary insufficiency secondary to sepsis. In these patients, one might see a worsening of pulmonary status following the administration of albumin and in these patients furosemide alone may be the treatment of choice.

41ST ANNUAL SCIENTIFIC ASSEMBLY 429

Surgical Management of Traumatic Intracardiac Inju· ries. Hartwell H. Whisennand ; Kenneth L. Mattox ; Rafael Espada; Arthur C. Beall, Jr. Blunt and penetrating wounds of the heart are being managed today with increasing success. Regardless of primary methods of management, with increasing numbers of patients surviving cardiac injuries, significant traumatic intracardiac defects requiring repair are being seen. These hemodynamically significant intracardiac defects secondary to trauma require diagnostic evaluation by cardiac catheterization and repair utilizing cardiopulmonary bypass. In recent years, an excess of 300 cardiac injuries has been managed at our city-county hospital. Among these, II patients had hemodynamically significant intracardiac defects. All but one were men . Seven of these lesions were secondary to stab wounds, 3 were from blunt trauma and I was caused by a gunshot wound . Three had traumatic ventricular septal defects, 3 had aortic valve insufficiency secondary to ruptured leaflets, 3 had fistulae from the ascending aorta to the right ventricle and I had mitral valve insufficiency from a knife laceration of the anterior papillary muscle, annulus, and septal leaflet. Initial management involved no treatment in 4, primary pericardiocentesis in 4 and suture closure of an external cardiac wound in 3. These intracardiac defects were repaired by suture closure of the shunt or prosthetic valve replacement utilizing cardiopulmonary bypass. All patients survived and remain asymptomatic.

Diagnosis of Gastric Acid Aspiration by Fiberoptic Bronchoscopy. john E. Wolfe ; Roger C. Bone; William E. Ruth Pulmonary aspiration of gastric contents is a common, serious and often fatal event. In experimental studies of acid aspiration, the importance of pH and volume of the aspirate have been emphasized. In the few clinical studies reported, the diagnosis of gastric acid aspiration was established by the observation of vomiting and suspicion of aspiration. In no study has visual observation of the tracheobronchial tree or other objective parameters to assess damage or observe presence of gastric material been used as criteria. Hemorrhagic tracheobronchitis has been described in experimental gastric acid aspiration. This pathologic change is readily recognized by direct visual observation of the tracheobronchial tree with the fiberoptic bronchoscope and allows diagnosis early in the clinical course of the patient suspected to have aspirated gastric contents. The present study describes the findings in 39 patients suspected of having aspirated gastric contents. In 34 patients, the findings of hemorrhagic tracheobronchitis and j or gastric contents within the bronchial tree were confirmed. Findings were documented by photomicrography. In the remaining five patients suspected of having aspirated gastric acid contents, gastric contents were not found. and tracheobronchitis was not present. Subsequent diagnostic procedures and clinical course documented other etiologies for these patients' respiratory distress. The present study would indicate that early fiberoptic observation of the tracheobronchial tree in patients suspected of having aspirated is helpful to establish a

430 41ST ANNUAL SCIENTIFIC ASSEMBLY

definitive diagnosis and to allow proper planning for clinical management. Coronary Artery Bypass: Long-Term Results in 5,165 Patients. Don C. Wukasch ; Robert ]. Hall; George ]. Reul, Jr.; Frank M . Sandiford; E. Ross Kyger; Grady L. Hallman; Denton A. Cooley From October 1969 through .-\pril ~0. 1975, 5,165 patients underwent coronary artery bypass at the Texas Heart Institute. To ascertain long-term results, follow-up data from one to five years was analyzed. For all patients undergoing coronary bypass without concomitant procedures, early mortality was 5.4 percent and late mortality was 2.8 percent. During the most recent year (1974). early mortality was 3.5 percent. Women experienced significantly higher early mortality (9.2 percent total series and 7. 1 percent in 1974). but experienced Jess late mortality (1.7 percent compared to 2.9 percent in men) . The most common causes of both early and late death were myocardial infarction, congestive failure and arrhythmias. Whereas early mortality was highest in pa· tients undergoing triple bypasses (6.4 percent compared to 5.3 percent for double and 3. 7 for single) . late mortality was higher in both double (3.9 percent) and single (2.5 percent) bypass groups compared to 1.8 percent in the triple bypass group. Five-year survival (Cutler curves) . including early and late mortality. was 90 percent for single bypasses, 87 percent for triple, and 85 percent for double with an overall 5-year survival of 85.9 percent. Average annual attrition was 2.8 percent per yea r. These data suggest that surgical treatment of patients with arteriosclerotic coronary artery disease significantly improves long-term survival.

Coagulation Factors Influencing Thrombosis of Aortocoronary Bypass Grafts. R . Zajtchuk ; G. f . Collins ; G. F. Schuchmann ; W. H. H eydorn ; T. E. Strevt')'; f. ] . Bergin Unsatisfactory technique or severely diseased distal coronary arteries are usually blamed for the early occlusion of aortocoronary bypass grafts. This study is based on the retrospective evaluation of ~0 patients for hypercoagulability who had occlusion of aortocoronary vein grafts within one year of surgery. The blood flow through the graft, measured at operation , ranged between 35 and 90 ml per minute. Five of the 30 patients had documented pulmonary emboli within 30 days of the operation . The following parameters were swdied in the patient group : generation of thrombin, antithrombin-III level, activated partial thromboplastin time, factor VIII assays, fibrinogen levels, platelet count and platelet adhesiveness. Normal values for these tests have been previously determined. Twenty-three of the 30 patients were found to be hypercoagulable, as evidenced by low a ntithrombin-III, high thrombin generation index and high factor VIII values. Three patients had abnormal platelet adhesiveness. All patients who had pulmonary emboli were found to be hypercoagulable. These data suggest that thrombin generation , serum antithrombin-III and factor VIII determinations may identify patients predisposed to pulmonary embolism and premature closure of the aortocoronary bypass grafts.

CHEST, 68: 3, SEPTEMBER, 1975

An Improved Noninvasive Plethysmographic Measure of Transthoracic Pressure during Maximal Expiratory Maneuvers: Theory. R . W. Zimmerer; D. R . Hazlett Reliable transthoracic pressure measurements require either a "stop-flow" technique or insertion of an esophageal balloon or esophageal pressure transducer. The former method is unsuitable for maximal expiratory maneuvers and the latter is unpleasant because it requires insertion of a catheter through the nose into the esophagus. An alternative method requiring rebreathing within a body plethysmograph has not prm·ed very practical. The perfection of fast-response. linear, prcssure-sensi-

CHEST, 68: 3, SEPTEMBER, 1975

tive transistors with negligible volumetric displacement encouraged this fresh look at the pressure independent flow and the airway resistive characteristics of the lung during forced expiratory maneuvers. The theory describes the interrelationships between lung compression by muscular effort and gas flow at the mouth during a maximal expiratory maneuver. Since lung compression precedes appearance of gas flow at the mouth, there is a net increase in box volume proportional to the increase in transthoracic pressure. The resulting high-speed pressure-How-volume curves provide a better noninvasive view of airway dynamics.

41ST ANNUAL SCIENTIFIC ASSEMBLY 431

Abstracts, Cecile Lehman Mayer Research Forum

The Mechanism of Abnormal Breathing in Asthma. E. R. Bleecker;/). f. Col/on ; f. A. Nadel ; IV. M . Gold The cause of the abnormal breathing pattern in asthma is unknown. Our experiments were designed to evaluate the role of the vagus nerves in the ventilatory response to inhaled Ao~cm·io~ mum antigen in conscious dogs. In 4 dogs allergic to Ascaris, the cervical vagi were implanted in permanent skin loops. The dogs were trained to exerdse on a treadmill and to breathe through a tracheostomy tube. Inhalation of antigen aerosol increased ventilation (78 percent ± 7) (mean ± SE), respiratory frequeiHY (243 percent ± II). air-How resistance (192 percent ± 34), and decreased tidal volume (-18 percent ± 2.5) . When conduction in the vagi was blocked hy cooling the skin loops with radiators, the ventilatory response to inhaled antigen was totally abolished hut air-flow resistance still increased (278 percent ± 60) . Since antigen-induced changes in airways are associated with release of histamine, we studied the response to inhaled histamine aerosol (I percent). Histamine produced a similar response to antigen, increasing ventilation (fiO percent ± 4 .5 ). frequency (158 percent ± 14), air-flow resistance (I 36 percent ± IIi), and decreasing tidal volume (:17 percent ± 2.5). Vagal cooling also abolished the ventilatory response to inhaled histamine. Following inhalation of terhutaline aerosol, histamine no lonl-(er increased air-flow resistance. hut still increased ventilation (47 percent ± 5) , frequency (156 percent± I 7). and decreased tidal volume (41 percent ± 3), indicating that the ventilatory response was not secondary to hronchoconstriction. Adding external resistances similar to those induced hy antigen or histamine did not increase ventilation nor did it cause rapid, shallow breathing. We conclude that antigen aerosol causes rapid, shallow breathing by stimulation of airway receptors with afferent pathways in the vagus nerves. Stimulation of these receptors may be due to antigen-induced release of histamine. (Supported in part hy Public Health Service grants H I.-Oii285 and HL- I 4201) .

Effect of Hyperoxia on 5-Hydroxytryptamine (5-HT) Uptake by Normal and Vitainin E-Deficient Rat Lungs. £. N . Bloc·k; A . B . Fisher Pulmonary 0~ toxicity is characterized by ultrastructural alterations of capillary endothelium followed by progressive destruction of lung parenchyma. Since pulmonary uptake of 5-HT is probably an energy-requiring process of lung endothel ium, we evaluated 5-HT uptake as a potential probe to detect early functional endothelial impairment due to o~ exposure. Isolated lungs from normal or vitamin E-deficient rats previously ex-

432 41ST ANNUAL SCIENTIFIC ASSEMBLY

posed to 100 percent 0 2 at I ata for 4-48 hrs, or 100 percent o~ at 4 ata for I hr. were ventilated and perfused with Krebs-Ringer bicarbonate, pH 7.4, containing 3 percent bovine serum albumin and 0.25,ul\l HC-5-HT. Uptake of 5-HT was calculated from the disappearance rate of 14C-5-HT from the perfusate and compared to uptake by lungs of air-exposed control rats. In 44 control rats fed a normal diet, 5-HT uptake by the lung was 0.78 ± 0.03 (SEJ\1) nmols j min and was not significantly different from rats exposed to 0~ at I ata for 4-12 hours. After 18 hours. there was a 20 percent reduction (P < 0.01 , n 9) in 14C-5-HT uptake. In vitamin E-deficient rats, 5-HT uptake in nmols j min was control (n 18) . 0.88 ± 0.05; 12-hr 0~ . 0.48 ± 0.09 (P < ll.lll); and 18hr 0~ 0.47 ± 0.04 (P < 0.01). 5-HT uptake by the lungs of normal rats exposed to hyperbaric 0~ (4 ata for I hour) was 0.55 ± 0.01 nmols j min (P < 0.001. n 5) and 0.41 ± 0.01 (P < 0.001 , n 5) 111 vitamin E-deficient rats. 5-HT uptake in normal rats returned to control levels 3 hours after exposure to hyperbaric o~. hut remained unchanged 3 hours postexposure in the lungs of vitamin E-defident rats. Pretreatment of rats with 0.50 mg superoxide dismutase IV appeared to accelerate retum of 5-HT uptake to control levels while pretreatment with reduced glutathione 12 mmol j kg IP or succinate 12 mmol j kg IP offered no protection . These results indicate that depression of 5-HT uptake hy the lung is an early and reversible alteration of lung function in rats due to hyperoxia , and this effect is potentiated by vitamin E-deficiency. This finding provides a sensitive metabolic indicator to evaluate the initial stages of o~ interaction with the lung.

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Ventilatory Stimulation by Salicylate: Role of Extracranial Receptors. Sa IIford J.evine A profound increase in ventilation (VE) is observed in salicylate intoxication . Previous workers have demonstrated that increases in arterial [H •] cannot explain this hyperventilation . However, the precise mechanism of this increase in VE is still not understood . Accordingly. sodium salicylate [150-250 mg j kg] was infused into chloralose anesthetized mongrel dogs ; VE increased 122 ± 24 percent and oxygen consumption (VO~) increased 125 ± 15 percent. A blood salicylate concentration of 42 ± 3 mg / 100 ml accompanied these ventilatory and metabolic changes ; arterial Pco~ and arterial fH •] decreased in all animals. Heads of dogs were then perfused entirely by a support dog with blood of unchanging gas composition; spinal cord remained intact. The carotid bodies lay within the rel-(ion of the perfused head ; the aortic bodies were denervated. Infusion of sodium salicylate into the bodies of these head

CHEST, 68: 3, SEPTEMBER, 1975

perfused animals consistently elicited increases in VE [149 ± 20) and increases in vo2 [131 ± 19], although significant amounts of salicylate did not reach the head or carotid body. In any case, when the same dose of salicylate was selectively administered to the head, increases in VE were limited to 18 ± 8 percent. It is concluded that extracranial receptors (other than the carotid and aortic bodies) account for a major portion of salicylate-induced hyperventilation. We have previously demonstrated that similar extracranial receptors mediate the increase in VE elicited by conventional uncouplers of oxidative phosphorylation. The present study demonstrates that large doses of salicylates also elicit increases in V0 2 ; therefore, the hyperventilation of salicylate intoxication may represent a particular example of the ventilatory response to drug-induced hypermetabolism. Isolation and Characterization of Type 2 Alveolar Cells. Robert Mason Synthesis of surface-active material and resistance to injury by oxidant gases are thought to be important properties of type 2 alveolar cells. Metabolic characteristics of these cells are difficult to define with intact lung because of the cellular heterogeneity. To overcome this difficulty, I have developed a method for isolating type 2 cells from normal rats. The method includes perfusing the lung to remove blood cells, allowing macrophages to ingest a heavy particle (an emulsion of fluorocarbon FC-75), incubating lung with trypsin, and separating the dissociated cells on a discontinuous gradient of albumin. The yield for all experiments (N=76) is 8.7 ± 3.7 X J06 cellsfrat (mean ± SD) , of which 69 ± II are type 2 cells and 92 ± 4 percent exclude trypan blue. The purity was quantified by the modified Papanicolaou stain, confirmed by electron microscopy, and checked with phosphine 3R, a compound that causes the lamellar inclusion bodies of type 2 cells to fluoresce intensely. These data suggest that type 2 cells have a relatively high activity of the pentose pathway which could be important for fatty acid synthesis for the production of surface-active material and production of reducing equivalents for resistance to oxidant injury and the type 2 cells are not the source of the high lactate production in perfused lung or lung slices. Harmonic Analysis of the Left Ventricular Pressure Waveform: An Approach to the Inverse Problem in Hemodynamics. David M. Mirois; Gary S. Kopf Most attempts to quantitate myocardial function rely on gross morphologic features of pressure waveforms to reflect the intrinsic properties of the ventricular myocardium. This inverse approach is complicated by the complex nature of the studied waveforms, each being composed of many simple sinusoidal waves of varying periods and amplitudes. Relationships between these basic waveforms and the function of the organ generating them were examined in 38 Rhesus monkeys by harmonic analysis of left ventricular pressure waveforms, recorded using micromanometer and digital computer techniques. In the basal state, harmonic content was closely correlated (r = 0.98) with hemodynamic state, as quantitated by rate, systolic and diastolic pressures, LVEDP and Vmax based

CHEST, 68: 3, SEPTEMBER, 1975

on a three element model. Hemodynamic indices were expressed as significant linear functions of harmonic terms (r = 0. 71 - 0.83), in patterns consistent with the principle of superposition. Harmonic terms could be expressed as a function of hemodynamic variables, suggesting a dependence of harmonic content on the functional state of the myocardium. In 18 animals, infusions .of dextran, methoxamine, propranolol, or ouabain were used to further assess this relationship. Results demon· strated significant correlation between changes in hemodynamic and harmonic parameters (r = 0.99) ; correlation between each harmonic term and the set of hemodynamic indices such that specific terms, eg, second harmonic cosine term, varied directly with contractility (r = 0.80) but not with loading, whereas others, eg, second harmonic sine term, correlated significantly only with loading; and that the patterns in these correlations were of such specificity as to permit construction of significant discriminant functions (P < 0.000 I) that accurately characterized the pharmacologically induced hemodynamic change in 85 percent (56( 67) of trials. Thus, harmonic analysis, by permitting study of basic waveform components, may be a useful technique for the inverse evaluation of myocardial function.

The Relationship of Pulmonary Capillary Permeability to Irreversible Hypotension following Hemorrhagic Shock and Reinfusion. William F. Northrup, Ill; Edward IV. Humphrey A group of control dogs (C) and a group undergoing hemorrhagic shock (S) to a mean aortic pressure (P ...) of 40 mm Hg for 2 hours followed by reinfusion had left (LTD) and right (RTD) thoracic lymph ducts cannulated. 125RISA was injected intra-arterially, lymph flow rates (Q) were monitored, and concentrations of 125RISA, albumin (alb), and globulin (glob) were determined in lymph and plasma at intervals for 4 hours. In C, Q,., 0 remained at .025 ml j min. Two S subgroups were defined : 7 responders (R) had Q,., 0 > 2 SD of mean C; and 7 nonresponders (NR) had Q,. 111 < 2 SD of C. There was a 6- to 10-fold increase in Q,. 111 of R. In contrast, Q,.,d fell from .7 to .44 ml j min in both R and NR, while remaining at .7 ml j min in C. In both R and NR, P80 returned to preshock values following reinfusion, but fell rapidly in R to 70 mm Hg by 3 hours, while remaining at 120 mm Hg in NR. The initial rate coefficient for lymph-plasma equilibration in the RTD lymph in R was 3-fold greater (-328 x I0-7 min-I) than the values for both C (-93 X I0-7 min-I) and NR (-113 X 10-7 min-I). The same pattern occurred in the LTD lymph but was less marked. After 4 hours in R, the RTD lymph / plasma ratio (L / P) for both alb and glob increased: for alb from .74 to .91 and for glob from .45 to .68. However, during the same time period in NR the RTD L / P for both alb and glob decreased : for alb from .74 to .51 and for glob from .45 to .30. The LTD L / P ratios changed less markedly. In R . it increased for both alb and glob: for alb from .85 to .94 and for glob from .67 to .89. In NR, the L j J> decreased for both alb and glob: for alb from .85 to .80 and for glob from .67 to .58. In C, the same L j P ratios remained constant over 4 hours. A 6- to 10-fold increase in the flux of both albumin and globulin in the RTD of R occurred, while little change was seen in NR. These data

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suggest that following shock and reinfusion, the pulmonary capillaries of some dogs have a greatly increased leak of albumin and globulin associated with increase pulmonary lymph flow and that these same dogs are subsequently unable to maintain their systemic pressure. Dogs who did not develop these permeability changes could maintain systemic pressure at relatively normal levels.

Restoration of Myocardial Metabolic Functions after Severe Ischemic Injury during Cardiopulmonary Bypass in Dogs Treated with Allopurinol. Luis H. ToledoPereyra; William G. Lindsay : john E. Foker The effects of myocardial ischemia during cardiopulmonary bypass remain a major problem in cardiac surgery. Although the molecular mechanisms are not completely understood, the loss of high-energy phosphate bonds during ischemia is important to the subsequent disrupted changes within the cell. This study was de-

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signed to determine whether or not allopurinol (AP) , a xa nthine oxidase inhibitor, would protect the myocardium during ischemic insult. Dogs were placed on normo· thermic cardiopulmonary bypass (CPB) with the aorta cross-clamped (AC) for 60 minutes. Serial blood samples were taken from the coronary sinus for potassium, lactic dehydrogenase (LDH) , and lactic acid. Left ventricular biopsies were obtained and assayed for adenosine triphosphate (ATP) . Our results suggest that chronic treatment with AP provided a significant protection to the myocardium during CPB and aortic cross-clamping. ATP returned more promptly to normal levels and LDH was minimally released. AP given immediately before surgery did not show the same results. It is possible that AP interferes with the breakdown of adenine and provides adenine nucleotides for the generation of high energy phosphate bonds for the reversal of ischemia. These findings offer a possibility for clinical application of allopurinol during long-term cardiopulmonary bypass.

CHEST, 68: 3, SEPTEMBER, 1975