42nd Annual Scientific Assembly

42nd Annual Scientific Assembly

ABSTRACTS 42nd Annual Scientific Assembly American College of Chest Physicians Atlanta, Georgia October 24-28, 1976 A Respiratory Intensive Care U...

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ABSTRACTS

42nd Annual Scientific Assembly American College of Chest Physicians

Atlanta, Georgia October 24-28, 1976

A Respiratory Intensive Care Unit (RICU) Patient Management System (PMS). Arnold Aberman, Ernest Hew, Toronto, Ontario \\'c have desig-ned and implemented a PMS, based on a dedicated minicomputer. to assist in the care of patients in our RIel '. Interaction with the RICU physicians, nurses and technologists is via a video terminal. The other peripherals include disc drives for data storage and a printer for hard copy output. The applications programs serve clinical, educational and research functions. I t is used to calculate drug dosages adjusted for various patient variables, such as renal function, ag-e. weight. etc. An infusion pump control program ensures the administration of the desired fluids and medications. Various hcmodvnamic and pulmonary physiologic measurcmcnts, t'l{ alveolar-arterial oxygen gradient, pulmonary shunt fraction. calculated P50, can be derived at the bedside. Ventilator settings for tidal volume and respiratory rate, addition or deletion of mechanical dead space and target arterial Pc02 based on automated interpretation of arterial blood gases are suggested for patients being mechanically ventilated. Algorithms assist the physician in the investigation and treatment of specific clinical problems. We have found the PMS to be invaluable in the management of critically ill patients in the RIClJ.

Hemodynamic Effects of Nitroglycerin Ointment and Sublingual Nitroglycerin: Reduction in Left Ventricular Volumes. [onathan Abrams, Koshy Kochukoshy, Albuquerque The effects of 2 percent nitroglycerin ointment (NO) and sublingual nitroglycerin (NTC;) were evaluated with serial echocardiographv for three hours in ten normal subjects. The two commercial :";0 preparations (NO-A and NO-B) as well as placebo ointment. were studied in a double-blind protocol. Results: Sublingual Nl'G· reduced echo-derived mean left ventricular (LV) end-diastolic volumes (EDV) and end-systolic volumes (ESV) maximally at five minutes by 13.8 percent and 17.8 percent, respectively. Significant reductions in LV volumes were still present at 15 minutes, and thereafter returned to control. Heart rate increased significantly at 5 and 15 minutes. Placebo ointment produced no hemodynamic changes. Both ~()s resulted in significant sustained decreases in LV EDV and ESV from 15 to 180 minutes. Maximal reductions in mean EDV occurred at 60 minutes (range 30-180 min) IlH..· asuring 14.4 percent (NO-A) and 20.1 percent (NO-B). Maximal reductions in mean ESV occurred at 30 minutes (ran~e I!)-IHO min) and were 23.3 percent and 20.3 percent, respectively. Heart rate and systolic blood pressure changed appropriately. In conclusion. NO reduces LV diameters and volumes for at least three hours. to a degree that is often greater than seen with sublingual NTC;.

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Significance of New Q Waves after Bypass Grafting: Correlations between Graft Patency, Ventriculogram and Surgical Venting Technique. Agop Aintablian; Robert I. Hamby; lruiin Hoiiman ; Daniel Weisz; Choudary Voleti; B. George WisolJ, Neui Hyde Park, l\/ew York New Q waves were observed in 56 (8 percent) of 671 patients undergoing saphenous vein bypass grafting. Forty-two of the 56 (75 percent) who had postoperative vcntriculograms and arteriograms are reported. New Q waves with .ventricular venting was 22 percent, and with atrial venting 6 percent (P 0.05) . Age, sex, duration of disease, severity of angina, previous myocardial infarction. main left lesions, completeness of revascularization, bypass or aortic cross clamp time did not affect the incidence of new Q waves. Postoperatively, ventriculograms were improved or unchanged in 26 and deteriorated in 16. Graft closure with Q waves and ventricular venting (27 percent), was twice those with atrial venting (15 percent). There was poor correlation between new Q waves and graft closure. Improved ventriculograIns correlated well with graft patency despite new Q waves. The etiology of new Q waves include ventricular trauma, conduction delays from surgery or venting, or true ischemic infarction. Infarction nlay be due to compromised arterial inflow in nonoperated diseased vessels, in vessels distal to anastomoses with patent grafts, or to graft occlusion.

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Abnormal Spirometry among Asbestos Miners and Millers with Normal Chest X-ray Films. Henry Anderson; Ming Chuang; Ruth Lilis; Willian} ]. Nicholson; Susan At. Daum; All Fischbein; William V. Lorimer; Irving ]. SelikoD, New York City In asbestos-exposed individuals, radiographic evidence of parenchymal fibrosis has been associated with a restrictive spirometry pattern (FVC percent pred 80 percent). However, asbestos exposure can result in a restrictive pattern without radiographic evidence of parenchymal fibrosis. We recently completed a survey of 1,215 chrysotile asbestos miners and millers. The examination included: comprehensive lifetime occupational, medical and MRC respiratory questionnaires; 14 X 17 PA chest x-ray film; spirometry using a SRL predictive screener and a Vertek 3500 Fleish pneumotachygraph and the predicted values of Morris et al; a complete physical examination. The x-ray films were interpreted by a panel of five readers using the ILO / DC Pneumoconiosis Classification. Increasing ILOjUC categories correlated highly with decreasing FVC percent pred (P .00(1), but did not correlate with obstructive findings. No radiographic evidence of parenchymal fibrosis was found in 446 men. However, 46 percent of these had FVC percent pred 80 percent and 15 percent had FVC percent pred 65 percent. The effects

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CHEST, 70: 3, SEPTEMBER, 1976

of duration of exposure, job category, dust index, smoking history and age are evaluated and correlations with clinical findings are made. Acute Effects of Varying Cigarette Composition on Airway Function. William Anderson; Mark Bright; Emery Lane; Janice Averitt, Louisville

heat. The accuracy of the area and depth of burn, the absence of bleeding, the slight tissue reaction and the minimal scarring make this new modality of importance in the management of stenosis and strictures and benign and malignant tumors of the trachea and bronchi. The characteristics of the carbon dioxide laser and the associated armamentarium and techniques will be reviewed. Twenty-five patients will be summarized who have had curative and palliative laser surgery for papilloma, early and late postintubation stenosis, granuloma, strictures and carcinoma of the trachea and bronchi.

Thirty-six chronic cigarette smokers were studied. There were 12 who smoked a high tar and nicotine cigarette (27 and 1.7 mg) : 12 a low tar and nicotine product (4 and 0.3 mg) and the other 12 were studied at the same intervals but did not smoke. The studies were those of puff profile and butt analysis to quantify the smoking. Vital capacity, FEV t .o, FEF2 5 - 75 and FIT 75-85 were used as an indication of airway function. The airway studies were done before, 5 and 15 minu tes after smoking. Although those smoking the low tar and nicotine cigarette apparently tried to compensate by increasing the volume of puff (P 0.01) and making the puff last longer (P 0.02) , smoking the low tar-nicotine cigarette did not cause any measurable alteration of airway function in comparison to the control group, not in comparison to their pre-smoking level. Smoking the high tar and nicotine cigarette resulted in a significant reduction in FEF25 - 75 and FEF 75-85 in comparison to both other groups (P 0.03) . Thus, under these conditions smoking one cigarette did not affect large airway function. The high tar and nicotine did cause a decrease in small airway function; no such effect was demonstrated following the low tar-nicotine cigarette.

The effect of isometric exercise (ISO) in patients with various types of left ventricular (LV) outflow obstruction (OB) is incompletely understood. Therefore, the LV response to ISO in six patients with severe dynamic LV OB (gradient 75 mm Hg) (IHSS) was compared to ten patients with fixed valvular obstruction (AS) (gradient 66 mm Hg). IHSS and AS exhibit similar responses to ISO in HR, MAP, SVR, CO and LVEDP, but in AS, while LVSP rises, the Grad is unchanged; in IHSS, the LVSP falls concomitant with decreased Grad. In AS LVSWI is fixed but declines in IHSS. Thus, while ISO is hazardous in AS, the reduction in Grad and decrease in LVSP may be beneficial in IHSS.

Quantification of Smoking in Patients with Smoking Related Disease. William H. Anderson; Mark Bright; Janice Averitt" Louisville

Disturbed Carotid Flow Velocity with Prosthetic Aortic Valves. Robert W. Barnes; Faith Wolberg; Edwin V. Miller, Ioioa City

Puff profile, butt analysis and smoking histories were obtained in 46 patients with lung carcinoma, 198 with ASHD, 124 with COPD, 120 with other diagnosable cardiorespiratory disease states and 222 controls. All were men who were chronic smokers. The groups were corrected for age differences by means of a linear adjustment using age as a covariant. The results disclose that the cancer patients had smoked longer, more cigarettes now and one year ago, smoked more before breakfast, and had a longer smoking time per cigarette. Their lifetime nicotine consumption was also greater and the tar lifetime consumption was greater than all other groups except the COPD. While the ASHD group was in most instances not significantly different from groups other than the cancer patients, their quantitative smoking parameters tended to be smaller than the other groups. The COPD group were seldom significantly different in the quantitative smoking aspects from all others except the cancer group, but were in the direction of being greater than the other groups. The results of this study strongly support the concept that in the so-called smoking related diseases, that smoking acts as a co-factor in conjunction with some other cause-perhaps constitutional-that is necessary for the development of a given smoking related disease state. Only in the instance of lung cancer did there appear to be any evidence for a dose-related effect.

This study evaluated the effect of prosthetic aortic valves on carotid artery blood velocity assessed noninvasively by Doppler ultrasound in 28 patients (19 tilting disc and 9 ball valves) . Velocity patterns were analyzed for: 1) rate-corrected velocity upstroke times, and 2) disturbed (low-velocity) sound spectral distributions mimicking post-stenotic alterations, graded as none, mild, moderate, or severe. The results were compared with values from ten normal subjects. The velocity upstroke time with ball valves, 0.12 ± 0.01 second (mean ± 1 SD) was significantly greater (P 0.01) than normal, 0.06 ± 0.01 second, or with tilting disc prostheses, 0.07 ± 0.01 second. With ball valves, the velocity pattern was normal in one and was disturbed mildly in five, and moderately in three. With tilting disc prostheses, the velocity pattern was normal in 13 and was disturbed mildly in four, moderately in one, and severely in one instance of paravalvular leak. We conclude that prosthetic aortic valves may alter carotid flow velocity, particularly with valve dysfunction.

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Laser Endoscopic Surgery of the Trachea and Bronchi. A I bert H. Andrews, [r.; M. Stuart Strong; Charles Vaughan; Bon B. Hartline, Chicago

The carbon dioxide laser produces a beam of infrared light which destroys tissue by its intense and sharply localized

CHEST, 70: 3, SEPTEMBER, 1976

Isometric Exercise in Patients with Dynamic and Fixed Left Ventricular Outflow Obstruction: A Comparison of Cardiovascular Responses. Najam Awan; Richard R. Miller; Louis A. Vismara; Anthony N. DeMaria; Ezra A. Amsterdam; Dean T. Mason, Davis, Cal

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Mechanical Means for Termination of Tachyarrhythmias. Benjamin Bejeler, Miami

Two modalities of mechanical stimulation were used to terminate paroxysmal atrial and ventricular tachyarrhythmias. External chest thump was used as the initial intervention for ventricular tachycardia. Temporary pacemaker or catheter induced mechanical ventricular or atrial extrasystoles were utilized for supraventricular tachycardias (flutter, AV junctional and paroxysmal atrial tachycardia) in the cardiovascular laboratory. If these methods were not successful, conventional drug therapy or electroconversion was utilized. Observations were made on 19 individuals having 23 episodes.

42ND ANNUAL SCIENTIFIC ASSEMBLY 419

Six individuals with ventricular aneurysms and nine episodes of ventricular tachycardia responded in six instances to a chest thump in the region of the paradoxical pulsation (66 percent). Three patients with three episodes of ventricular tachycardia and without ventricular aneurysl1ls responded one out of three to chest thump (33 percent) . Seven patients exhibited paroxysmal atrial tachycardia, five episodes were converted to sinus rhythm (71 percent). three with a right ventricular extrasystole and two with atrial extrasystoles. Two individuals had three episodes of junctional tachycardia, one converted with a right ventricular extrasystole. One patient with atrial flutter converted with a right ventricular premature beat. All patients not responsive to mechanical means were treated successfully with drugs or cardioversion. Patients with paroxysmal atrial fibrillation were uniformly unresponsive to mechanical conversion. The mechanism by which mechanical stimulation of the heart allows conversion of these arrhythmias is unknown, but it is probably sirn ilar to that of electrical cardioversion, namely depolarization of a large segment of ventricular muscle with interruption of the reentry circuit and emergence of a higher pacemaker rhythm. Mechanical stimulation of the heart for conversion of paroxysmal tachyarrhythmias offers, in the appropriate setting, a fast, safe and often successful means of terminating these arrhythmias, without precluding other means of therapy. VA Cooperative Study of Surgery for Coronary Artery Disease Using Internal Mammary Artery Implantation. Joginder N. Bhayana; Andrew A. Gage; Herbert N. Hultgren; Katherine M. Detre; Timothy Takara, Buffalo A randomized controlled study for evaluating the efficacy of internal mammary artery implantation (IMA) in prolonging life and improving quality of life in patients with stable angina was started in 1966. One hundred and forty-six men patients entered the study through 1969 following coronary angiography. Seventy-five were randomly assigned to medicine and 71 to surgery. Surgery patients received one or two IMA implants as indicated. At initial evaluation, baseline characteristics such as duration of angina, history of previous myocardial infarction, congestive heart failure, functional status (New York Heart Association), left ventricular contraction abnormalities and number of major arteries involved, were similar in both groups. All patients were followed up to 71/ 2 years. Cumulative survival curves showed that at the end of seven years, 56 percent of patients in the medical group and 53 percent of patients in the surgical group were alive (P-NS). Our study shows that IMA implants have no beneficial effect on longevity. Data on quality of life will be presen ted. The First Cigarette: Effects on Small Airways in Baboons. Frederick R. Bode; Bruce M. McCullough; Waldemar G. Johanson, Jr., San Antonio The occurrence of airway disease in smokers may be determined by varying physiologic responses to cigarette smoke. In preliminary studies of 22 baboons enrolled in a long-term smoking project. we determined the acu te effects of their first cigarette. Baseline studies included lung volumes, static voluille-pressure curves, closing volume (CV) , and maximum expiratory flow volume (MEFV) curves during air and 80 percent hcliurn-Zt) percent oxygen breathing. Smoke exposure consisted of 15 forced inhalations of 15 ml smoke plus ,")0 percent of the inspiratory capacity. CV and MEFV curves

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were repeated postsmoking. Although changes were small after smoking. CV increased in 16/22 (P 0.(01) and the lung volume at which maximum expiratory flows of air and helium became identical (VisoX') increased in 11/22 (P 0.005), suggesting increased peripheral airways obstruction. Pattern analysis of MEFV curves postsmoking showed bronchoconstriction clearly in eight animals. Longitudinal studies of these animals I1lay reveal why only some smokers develop chronic airway obstruction.

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Initial Clinical Experience with a New Cardiac vice-The Pulsatile Assist Device (PAD). David Frederick O. Bouiman, Jr.; Eduardo N. Parodi; Haubert; Richard N. Edie; Henry At. Spotnitz; emtsma; [ames R. Maim, Neui York City

Assist DeBregman; Susan M. Keith Re-

The advantages of intraoperative counterpulsation with intraaortic balloon pumping (IABP) are well documented. A new pulsatile assist device (PAD) has been developed to convert, in a simple fashion, roller pUlnp flow to pulsatile flow. In addition, the PAD can be used as an arterial counterpulsator before and after cardiopulmonary bypass (CPB). The PAD is inserted in the arterial line close to the aortic root. The device consists of a flexible valveless balloon through which the arterial blood flows. The balloon is contained within a rigid plastic housing which is connected to a standard intra-aortic balloon pUlnp, thereby enabling the blood filled balloon to be squeezed. The PAD was employed in 55 adult patients undergoing open heart surgery for coronary artery and/or valvular heart disease. Thirty of these patients were NYHA class 3 or 4 or had ejection fractions of 0.4. The device functioned as a hemodynamically effective counter pulsator before and after CPB. During CPB, pulse pressures of 40-50 mm Hg were readily obtained. Urinary outputs during ePB were increased on the PAD when compared to a control group (7.51 ± 1.22 mlj min vs 4.53 ± .73 ml j min) . In addition, during CPB, coronary graft blood flow (CBF) increased an average of 22.4 percent with the PAD, and after CPB, CBF increased an average of 27.7 percent. Free plasma hemoglobins after CPB were not elevated. Only one patient had a perioperative myocardial infarction and this patient was successfully treated with IABP. It is suggested that the PAD is a simple and reliable device for both intraoperative counterpulsation and for the creation of pulsatile CPB. More significantly, use of the PAD nlay decrease both the incidence of perioperative myocardial infarction and the need for postoperative IABP.

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Echocardiographic Correlates of Left Ventricular Hypertrophy Diagnosed by Electrocardiography. Patrick J. Browne; Alberto Bench imol; Kenneth B. Desser; Sergio V. Cabizuca; Connie Sheasb», Phoenix Echocardiography (ECHO) was performed in 28 consecutive patients who manifested accepted criteria for left ventricular hypertrophy (LVH) on their elcctrocarcliograrns. All such subjects had clinical and catheterization diagnoses compat ible with the ECG findings. No patient had asvmrnct ric septal hypertrophy. Mean (± 1 SD) ECHO measurements (in em) for the study group were: interventricular septal (IVS) thickness. 1.4±0.26; left ventricular posterior wall thickness (LVP'V), 1.3±0.28; left ventricular internal dimension (LVID), 4.8± 1.1. Four groups of patients were identified: group I, 19 (68 percent) who had an increase of both IVS and LVPW; group 2, three subjects (II percent) with

CHEST, 70: 3, SEPTEMBER, 1976

isolated enlargement of the LVID; group 3. two patients (7 percent) with increased IVS, LVP'V and LVID and group 4, four subjects (14 percent) with normal ECHO measurements. In the latter group, there were two patients with aortic stenosis (transaortic gradients in mm Hg == 60 and 90) , one subject with cardiomyopathy and a single patient with hypertensive heart disease. It is concluded that: patients with heart disease .and ECGs diagnostic of LVH l11ay have normal ECHO measurements despite clinical and catheterization evidence compatible with that diagnosis; isolated increase of LVID is a rare finding in the presence of LVH on the ECG; concentric LVH is the most frequent ECHO correlate of LVH on the ECG; the presence of normal measurements for IVS, LVPW and LVID should not be the sole basis for excluding significant LV disease in subjects with LVH on the ECG.

cordingly, sputa encompassing a wide range of viscoelastic properties were applied to frog palates exhibiting normal beating cilia but whose endogenous mucus was depleted by dithiothreitol, and the velocity at which they were transported measured on a dissecting microscope. Six to II samples were thus tested on each palate. The results showed that the fastest transport, per palate, corresponded to sputa whose viscosity and elastic modulus fell within the range of 15003000 poises and 10-25 dvnes/cmz respectively. 'rhus, these represent the optimal rheological values. Transport velocity decreased when the values for sputa viscoelasticity fell above or below the optimal range. The latter is of particular importance and it indicates that vigorous clinical attempts at f1uidification may hinder rather than promote mucus clearance.

Atypical Myobacterial Cultures: Disease or Distraction? Bruce D. Buchanan, San Francisco

Is Hypercapnia Complicating Metabolic Alkalosis A Rare Clinical Entity? Bart Chernoui, Clifford It'. Zioillich, Denver

Atypical mycobacteria were recovered from 136 of 2,237 patients during the period May, 1967 to November, 1973. Reports of 3,920 cultures from 16 sources were analyzed. Atypical mycobacterial disease was identified in 50 patients (group A) and atypical organisms were casually isolated in 86 patients (group B). Two differences in the groups were detected: all subjects in group B had less than four positive cultures compared with only 13 of 50 patients in group A (this portion of group A was designated group At); in those patients for whom colony counts were available, 97 percent in Group B had cultures with less than ten colonies per plate while only 8 of 19 cultures submitted by Group At had colony counts of less than ten per plate. These features significantly distinguished the populations (P .001). The evidence suggests that the presence of more than ten colonies of an atypical mycobacteria on a culture plate is a prerequisite to the diagnosis of atypical mycobacterial disease.

Hypercapnia complicating metabolic alkalosis (MA) is considered a rare event. \Ve observed an alkalotic patient with hypercapnia whose arterial carbon dioxide tension (PaC0 2 ) reached 84 mm Hg. Clinical and postmortem evidence failed to reveal an etiology for the hypercapnia, other than as a response to MA. This prompted us to review all the arterial blood gas (ABC) determinations (~==8,350) performed on 4,251 patients at Colorado General Hospital over a six-month period. One hundred eleven patients (2.6 percent of total) had ABC evidence of MA (pH ~ 7.45, bicarbonate ~ 30.0) . Of these III patients, 43 had known lung disease and were excluded from further study. Of the remaining 68 patients with MA and no lung disease, 38 (56 percent) had hypercapnia (PaC0 2 ~ 43) in response to MA (normal Denver PaC0 2 34-38) . Means (± SEM) for these 38 patients were: pH i.48 ± 0.002, bicarbonate 34.9 ± 0.4, and PaC0 2 4i.0 ± 0.4. We conclude that hypercapnia in response to MA is a common clinical entity.

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Hypersensitivity Pneumonitis or Sarcoidosis? George W. Burke; Edward A. Gaensler; Charles B. Carrington; Raj Gupta; Muiris X. Fitz.Gerald, Boston

We reviewed the clinical and pathologic findings in all 63 patients followed by our laboratory who had noninfectious granulomatous lung disease confirmed by open lung biopsy. Twelve had berylliosis. Fifty-one had been diagnosed as sarcoidosis. Histologically, four among the latter had fewer granulomas, prominent interstitial reactions with plasma cells. and more severe bronchiolitis-features suggestive of hypersensitivity pneumonitis. Although these four were chronically ill, they differed from sarcoidosis in their tendency to have fluctuating symptoms and physiologic changes, and normal chest roentgenograms when functional impairment was severe. In the two available for further studies, serum precipitins were present against multiple organisms contaminating their home humidifiers. Both improved following removal of these systems. Clinical and pathologic similarities between sarcoidosis and chronic hypersensitivity pneumonitis may result in failure to recognize the latter, particularly in patients exposed to environments which are not easily recognizable as antigen sources. Mucus Viscoelasticity and Mucociliary Clearance. Tz.eng M. Chen, Mauricio ]. Dulfano, Brooklyn

Our aim was to define the relationship between mucus rheology and its transport by mucous membrane cilia. Ac-

CHEST, 70: 3, SEPTEMBER, 1976

A Comparative Study of Gas Transport and Ventilation Inhomogeneity in Diffuse Interstitial Lung Disease. Edward H. Chester; Hugo D. Montenegro; Gerald M. Fleming, Cleveland

We studied diffuse interstitial lung disease (IlILD) in 116 patients; 64 had pulmonary sarcoidosis and 52 had other forms of DILD. Ventilation inhomogeneity was assessed with arterial-end tidal CO 2 gradients, P (a-ET) C0:J.' physiologic dead space (Vn/V T ) and single-breath N 2 rise (SBN 2 ) . Gas transport was assessed with alveolar-arterial O 2 gradients, P (A-a) 02 and carbon monoxide steadystate diffusing capacity (D s s ) . Ventilation inhomogeneity, as measured by P (a-ET) CO 2 , Vn/V,., and SBN 2 was more prevalent and more severe in the non-sarcoid group than in the sarcoidosis group. P (A-a) O 2 at three levels of oxygenation and during exercise were larger in the non-sarcoid group than in the sarcoidosis group, (37 ± 14 vs 27 ± 12 at 21 percent FI0 2 resting, 2:; ± 11 vs 18 ± 9 at 14 percent FI0:J., 105 ± 35 vs 86 ± 39 at 100 percent FI0 2 and !)() ± 15 vs 37 ± 17 at FI0 2 during exercise) . When these values were adjusted for age-predicted normals, the P (A-a) a:! was equivalent for both groups indicating a similar magnitude of oxygen transport dysfunction. We conclude that ventilation inhomogeneity is more prevalent and more severe in non-sarcoid DILD patients than in sarcoidosis and oxy~en transport dysfunction is similar for sarcoidosis and non-sarcoid DILD.

42NO ANNUAL SCIENTIFIC ASSEMBLY 421

Effects of Aromatic Medication by Inunction and Vaporizer in Chronic Bronchitis. Sati[ord Chodosh , Boston In a doublc-hlind. crossover design. we exposed stable hurnan out-patients with chronic bronchitis to Vaporub or placebo. each for four days. bv thorax inunction in one study; and by vaporization with a De\'ilhiss rnodel 133 steam vaporizer in a second study. Sixteen patients completed each of the studies. Dailv examinations included subjective symptoms. physical findings. qualitative and quantitative sputum cell determinations. sputurn gram stains and cultures, sputum physical properties and chemistr ies. and pulmonary function tests. There were essentially no significant differences between placebo and Vaporub for svmptoms, physical findings, sputum bacterial flora. sputum immunoglobulins and lysozyme. Statistically significant favorable results included increase of ;,Z uiuo phagocytosis by both sputum neutrophils and macrophages and decrease of sputum physical properties. Exfoliated bronchial epithelial cells were increased. The impairment of bronchopulmonarv host defense against bacteria noted by others in rodents is not supported by these findings in humans. which suggest enhancement of phagocytosis.

Tuberculosis: Changing Drug Resistance Patterns in a Large Southern California Hospital-I969-1976. •\Iichael G. Cleary; Brenda E. Aslikar: Mirja S. Bis!l0IJ, 'Torrance, Cal. Comparison of results of tuberculosis drug susceptibility studies performed at our hospital frorn 1969 to 1976 reveals that both primarv and secondary resistance to isoniazid (INH) has increased markedly. Studies from 1969 to 1972 reveal only 1:") of 260 patients (5.R percent) with organisms resistant to I~H. Frorn March. 19i5 to April. I~ifi. 2i of 98 patients (27.6 percent) demonstrated INH-resistant organisms. Ethambutol (EMB) resistance has also increased; 15 of 260 patients (5.8 percent) from 1969 to 1972 and 14 of 98 patients (14.3 percent) from March. 1975 to April, 1976 demonstrated resistance. The increases in both I~H and El\fB resistance are highly significant (P .005). Resistance to streptomycin and para-aminosalicylic acid has not changed significantly. The striking increase in resistance to I~H and EMB mav well influence our choice of initial antituberculosis chemotherapv in the future and certainly points out the need for more extensive utilization of drug susceptibility studies in our population.

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Myocardial Protection by Methylprednisolone. john E. Codd; Robert D. lVeins: Hendrick B. Barner; George C. Kaiser; Vallee L. Willman, St. Louis Although the use of corticosteroids in the management of acute nonoperative myocardial infarction (MI) is controversial. it has been felt to be of benefit in the management of other entities. Methvlprednisolone (MP) effectiveness in prevention of perioperative Ml was assessed by serial ECG and serum LDH. SG()~r. CPK and CPK-l\fB during the postoperative period in 150 patients. Seventy-five of these. randomly selected, received 2 gIll MP Y2 hr prior to institution of cardiopulrnonary bypass (CPB). There was no difference between the groups in operative technique. patient age. previous MI. angina severity. graft number, CPB duration, myocardial ischemia duration or graft patency. The only operative death occurred in the MP group. Nine patients in

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each KHHlp demonstrated ECG evidence of III yocardial injury. Enzymes did not further discriminate in the incidence of MI. Methylprednisolone did not reduce the incidence of perioperative myocardial injury during CAB(;.

Bronchodilator Volume of Isoflow: Studies in Patients with Chronic Obstructive Lung Diseases. Burton AI. Cohen, Elizabeth, JVe1.l' jersey Inhalation of a bronchodilator (metaproterenol) aerosol has been substituted for helium rox ygen breathing in the technique of Hutcheon et al to determine the volume in which expiratory flow rates were identical (volume of isoftow, Viso~') before. and three minutes after. rnist exposure for 60 unselected patients with chronic ohstructive pulmonary diseases. The paired MEFV curves were superimposed and matched at residual volume if the vital capacities were unequal; bronchodilator VisoV. expressed as a percentage of FVC. was compared to changes in I-VC, FEV).(). MEFR and PEFR following inhalation. The mean visov (31.61 ± IO.!>3 percent) exceeded the figure for normal non-smokers previously reported (7.29 ± 3.35 percent) . Although the mean rises in gToup test indices were modest, the magnitude of the changes rose with progressive increases in vtsov. with significant differences apparent for all values except FVC beginning above a 30 percent volume of isoflow. The mean VisoV for nine subjects with individual increases of 15 percent or more in FEV).o was 39.62 ± 11.02 percent, all four spirometric indices for these patients rose significantly (P == 0.05 or better) after the spray. Bronchodilator Viso~ may well be a valid index of potential responsivity to effective therapy. but cornparison of this approach with helium/oxygen breathing will be necessary to determine whether the two methods provide the same physiologic information.

Newer Aspects of Air Pollution (Western New York State Study). E. M. Cordasco; Herbert Gregory: H. S. Van Ordstrand; M. Popouici; james Goodrich, Cleueland During the past three years. approximately 2.000 people have been tested in a screening outpatient clinic study of Niagara County and part of Erie County of the western New York state region by the i\; iagara Frontier Environmental Health Research Foundation. The purposes of the study were to determine the relationship (if any) of specific air pollutants to the increased incidence of chronic obstructive lung disease in this region, and to formulate possible national air quality standards for new pollutants. particularly chlorine gas and other associated newer pollutants. Results disclose that the salient factors associated with chronic obstructive puhnonary disease with increased respiratory symptoms are: cigarette smoking. one pack or greater a day over a rninirnum of a five-year period; chlorine gas levels beyond 0.02!> parts per million over a 24 hour period; particulates. settlable beyond 100 mcg per cubic meter. Other newer pollutants are also under investigation. notably henzpyrenes and cadmium, to ascertain what relationship (if any) these agents may have to the incidence and etiology' of chronic obstructive lung disease. It is our opinion. based on these data. that chlorine gas levels beyond .025 parts per million. are related to increased health hazards. Therefore. we strongly urge that arnhient levels of .025 be adopoted as a National Air Quality Standard by the Environmental Protection Agency.

CHEST, 70: 3, SEPTEMBER, 1976

Closed Chest Biopsy Procedures in Immunosuppressed Patients. joseph H. Cunningh am; Donald C. Zavala; Robert J. Corry; Lon l'J'. Keirn, Iowa City Eighty-two dosed chest lung and bronchial biopsy procedures were performed in 54 immunosuppressed patients: 23 renal transplants, 26 lymphoreticular malignancies, and 5 other disorders. A specific diagnosis was obtained in 13 of 31 (42 percent) transbronchial biopsy procedures, 10 of 31 (32 percent) bronchial brushings, II of 17 (65 percent) percutaneous trephine lung biopsies and 3 of 3 (100 percent) percutaneous needle aspirations. Hemorrhage complicated 26 percent of the transbronchial biopsy procedures and 17 percent of the percutaneous trephine biopsies, whereas pneumothorax occurred in 19 percent and 60 percent respectively. Approximately half of the patients with pneumothorax required transient chest tube placement. Hemorrhagic complications in patients undergoing transbronchial hiopsy occurred three times as frequently among the uremic patients (5/11, or 45 percent) as compared to the nonazotemic patients (3/20, or 15 percent) . Only one of five patients with thrombocytopenia (9,000-60,000 platelets) experienced mild hemorrhage after transbronchial biopsy. Of the 54 patients, 20 (36 percent) died 2-60 days postbiopsy, but no fatalities were related to the biopsy procedure. Brush biopsy alone proved to be the safest procedure, but had a lower diagnostic yield. Trephine and transhronchial biopsy produced better diagnostic results but with a higher incidence of complications. Both of these procedures yielded comparable results in diagnosing both infectious and neoplastic diseases. The diagnostic yield was augmented to 48 percent when a combined transbronchial biopsy and bronchial brushings were done. Because of the high incidence of hemorrhage in immunosuppressed patients (29 percent) , and especially in patients with uremia (45 percent), caution is advised in considering these patients for dosed chest biopsy procedures. Lung biopsy results did not influence the overall survival.

Use of Lidocaine in Atrial Fibrillation and Atrial Flutter. Daniel T. Danahay ; Wilbert S. Aronoui, Irvine, Cal. The effect of lidocaine on ventricular rate (VR) was investigated in 16 atrial flutter (AF) patients and 35 atrial fibrillation patients. Lidocaine (mean dose 100 mg) was injected intravenously over 20 seconds with continuous electrocardiographic recording for five minutes before and at least 10 minutes after lidocaine. The atrial rate decreased in 15 of 16 AF patients (94 percent), mean maximal decrease 26 heats/min (P 0.(01). In atrial fibrillation patients, the mean VR increased 6 beats/min (P 0.01). In three of 16 AF patients (19 percent) and three of 35 atrial fibrillation patients (9 percent) , the VR increased more than 20 beatsj min (P 0.001). VR changes in AF and atrial fibrillation and atrial rate changes in AF occurred at therapeutic lidocaine revels, at all serum potassium levels, and despite therapeutic digoxin levels. Lidocaine-induced VR increases are common in atrial fibrillation and AF and appear mediated by atrial slowing.

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Measurement of Diaphragmatic Length in Normal Individuals and Patients with COPD. Joseph Danon ; Howard C. Fish man; John Lin; Muhammad Sharif; Walter S. Druz; John T. Sharp, Hines, Ill. Chest x-ray films were taken at FRC and TLC on a group of normals and COPD patients, and the length of the diaphragm

CHEST, 70: 3, SEPTEMBER, 1976

in the PA projection was measured from these films. If tlie actually measured length at FRC was bigger or smaller than the calculated, this was assumed to be due to lengthening or shortening of the muscle proper. which was assumed to 1)(' 46 percent of the total length (measurements done on 2H cadavers showed that in the latero-Iateral diameter of the diaphragm the muscle averaged 46 percent of the total length, the rest being tendon) . The amount of lengthening- or shortening was added to or subtracted from the ill-situ leng-th of the muscle proper, and the result expressed as percentage of the in-situ length of this muscle, In normals, the diaphragmarie length at FRC was around 90-140 percent of their insitu length, at TLC it shortened to around 65-100 percent of the ill-situ length. In COPD, the diaphragmatic length at FRC was considerably shorter than the ill-situ length. In patients where the diaphragm at FRC was longer than 40 percent of the in-situ length, the diaphragm further shortened at TLC. In contrast, in those who had initial lengths smaller than 40 percent the diaphragm did not shorten further at TLC or during inspiratory effort against an occluded airway. These patients showed actual inspiratory ascent of the diaphragm. These findings cannot be explained by the classic length-tension diagram of skeletal muscles, but they fit nicely into the length-tension relations which we measured on dogs' diaphragms. In dogs we found maximal active tension at about 125 percent of in-situ length, and zero tension only when the muscle was shorter than 43 percent of in-situ length. Application of this relationship to the present measurements on humans suggests that the diaphragms of most normals at FRC are stretched considerably beyond their resting lengths. When they inspire to TLC, the diaphragm usually remains within the relatively flat part of its length-tension curve and loses only 10-40 percent of the maximal tension. The diaphragms of patients with large FRCs operate on the steep portion of the length-tension curve and sacrifice considerable tension to achieve more shortening. In patients whose diaphragms at FRC are shorter than 40 percent of the in-situ length, the diaphragms apparently do not generate appreciable tension and are pulled up dur ing further inspiratory efforts.

Lipid Deposition in Pulmonary Alveolar Macrophages after Cigarette Smoke Exposure: A Morphometric Study. Paul Davies; Clinton Sornberger; Helen Benes; Gail Korman; Gar)' Huber, Boston The ready availability of alveolar macrophages (AM), by fiberoptic bronchoscopy in man or by lavage of animals, makes them potentially useful early indicators of lung disease. To study the effects on the lung of chronic experimental cigarette smoke inhalation, we have developed quantitative techniques for defining alterations in the structure of AM. In AM recovered by bronchopulmonary lavage from CD male rats exposed for 30 consecutive days to whole cigarette (2RI Kentucky reference tobacco) smoke, the most striking change noted was the cytoplasmic deposition of lipid. Lipid inclusions were specifically identified within AM by oil red 0 staining. In electron microscope preparations, these structures were moderately osmiophilic and resembled lipid vacuoles. Ultrastructural morphometry was used to determine the sub-cellular distribution of the lipid, as well as other structural components, with 419 whole profiles of cells from non-exposed controls and 319 from smoked animals photographcd ·at constant magnification and analyzed by pointcounting with a Weibel test lattice. The maximum diameters of profiles of lipid vacuoles were also measured. Stercologic

42ND ANNUAL SCIENTIFIC ASSEMBLY 423

calculations gave a volume density of lipid vacuoles per unit volume of total cytoplasm of 1.53 percent in control cells. After cigarette smoke inhalation. this value rose to 12.68 percent (P 0.001) with an eight-fold increase in the number of lipid vacuole profiles per cell profile. Size distribution studies gave mean vacuole profile diameters of O.9p. and 1.25p. in control and smoked cells, respectively. although both groups shared a similar modal diameter of 0.85p.-O.95p., indicating, perhaps. an optimal size for a cytoplasmic lipid inclusion. Although the precise origin of lipid in AM has not yet been determined, its relation to cell and tissue dysfunction may be considerable. With its ability to precisely detect pathologic changes in a cell population, morphometry has a powerful potential to identify very early structural alterations in a study of lung injury and the development of lung disease.

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The Carboxylic Ionophores-A New Group of Cardiotrophic Agents. Norberta T. de Guzman, Berton C. Pressman, Miami The introduction of ion-permeability inducing agents (ionophores) in the biological field provided a unique approach in the pharmacologic modifications of organ functions. Our discovery of the poten t inotropic effects of X -537A has been extended to other members of the carboxylic ionophores (CI) including Monensin, Salinomycin, A-204, X-206, Lysocellin, Dianemycin and Nigericin. Studies in anesthetized normal and infarcted dogs and isolated guinea pig hearts showed that CI increase the force of myocardial contraction and heart rate, dilate the coronary arteries and decrease total peripheral resistance, which all translates into increases in cardiac output, coronary flow and enhancement of left ventricular work efficiency. The mechanism of action of CI in intact animals involves their capacity to increase intracellular Na + in exchange for K + thus triggering increase Ca + + exchange and releasing neurohormones, ie catecholamines and glucagon. The hemodynamic effects of CI provide an ideal therapeutic approach in pump failure after myocardial infarction. Pheochromocytoma in the Modem Context. Norman C. Delarue; John Morrow; James Kerr; Ronald Colapinto, Toronto The hypertensive patient faces an uncertain future. Search for potentially curable disease is, therefore, eminently worthwhile. It has become increasingly productive because of the specific diagnostic aids now available and the present safety of surgical intervention. Detection and localization of pheochromocytoma allows a planned surgical approach. Correction of hypovolemia pre-. operatively ensures a safe postoperative course. The use of blocking agents preoperatively and their peroperative availability avoids the hazardous hypertensive crises and arrhythmias which colored earlier surgical experience. Monitoring of central venous pressure and arterial pressure, as well as the electrocardiographic tracing during the operative procedure permits prophylactic therapy when necessary. The present series of 30 patients compares the current situation with earlier experience in the same institution. The incidence of multicentric tumors and malignant change has been lower than usual (less than 10 percent) in this group of patients, although abdominal exploration remains the approach of choice in most cases. The treatment of the solitary tumor has now become straightforward. Management of the familial syndromes and malignant disease still requires careful scrutiny.

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Presystolic Anterior Septal Motion-A New Echocardiographic Sign in Hypertrophic Cardiomyopathies. Vincent R. deMello; Robert E. Kleiger; Kent Kreisman, St. Louis Although abnormal septal thickness is a well known abnormality of hypertrophic cardiomyopathies (HCM) analysis of septal motion particularly in presystole has received little attention. Amplitude of presystolic anterior septal motion (PASM) was analyzed in three groups of patients: HCM (n= 33), normals (n=25) and patients with decreased left ventricular compliance (DL VC) (n=20) by the echocardiographic criterion of decreased E to F slope of the anterior leaflet of the mitral valve. All patients were in normal sinus rhythm and the PASM occurred simultaneously with the A wave of the anterior leaflet of the mitral valve and followed the P wave of the ECC. The hypertrophic patients were divided into non-obstructive (n=ll) and obstructive (n=22). It was seen that PASM occurs more frequently and its amplitude is significantly increased in HCM. Within this group, PASM did not correlate with septal thickness, ejection fraction, or the E to F slope. We believe increased PASM represents the increased contribution of atrial contraction to left ventricular filling. In conclusion PASM 0.2 em was seen only in HCM and represents a new echocardiographic criterion.

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Effects of Cardiac Pacing in Acute Carbon Monoxide Intoxication in Dogs. Elias Dergal; Hassan Hodjati; Leo Goldbaum; Karel Absolon, Washington, D.C. Previous studies with carbon monoxide in dogs demonstrated ischemic electrocardiographic changes. In the present study three series of five dogs each were given 2, 5 and 10 percent CO respectively. All developed progressive sinus bradycardia, hypotension and cardiac standstill. The carboxyhemoglobin average levels in the first series were 24 percent (13-35); in the second 54 percent (45-65); and in the third 69 percent (50-76). A fixed rate pacemaker with the lead placed epicardially reverted the sinus bradycardia to normal sinus rhythm; as a result 5~ percent (8 of 15) of the dogs survived, compared to no survivals in the control group. Also, observed was an increased survival rate in dogs with higher hematocrits. The Hb appears to bind the inhaled CO, decreasing the dissolved CO fraction which is thought to block the cardiac cytochrome system. Cardiac pacing and red cell transfusion is the probable treatment of choice in CO poisoning. A Multi-Disciplinary Approach to Weaning of RespiratorDependent Patients. Gautamkumar Desai; Nathan S. SeriD; Faroque Khan; Joan Mogil; Errol Hunte, Queens, New York Inability to wean a patient from a respirator is a not uncommon cause for transfer to a respiratory intensive care unit. This study concerns 16 such patients who were transferred to the respiratory intensive care unit of this institution over a three-year period when weaning could not be carried out at the referring hospital. All had COPD and three had associated ASHD with left ventricular failure. Their mean age was 67 years; there were six women and ten men. Their mean period of continuous mechanical ventilation prior to transfer was 29 days. Factors commonly present in these patients contributing to their inability to be weaned were: social and psychological difficulties, based on a profound fear of sudden death if removed from the respirator, depression over their chronic illness, and interpersonal strife with the spouse, making the

CHEST, 70: 3, SEPTEMBER, 1976

prospect of discharge unpleasant; metabolic abnormalities, the most C0l111110n of which were hypokalemia, hypochloremia, anemia and hypoalburnencmia: continuing severe airway obstruction or co-existent passive congestion of the lungs from ASHD, both of these reflected in a vital capacity and negative effort which were so low as to indicate that they were not ready to be weaned. A multi-disciphnarv effort was undertaken to overcome these problems and will be discussed. Ten of the 13 patients were successfully weaned. extubated and discharged. The time for weaning was unrelated to the duration of their prior mechanical ventilation. Two died in the hospital, and one was discharged with a permanent tracheostomy. It is our feeling that difficult weaning problems Inay be approached successfully and permanent invalidism and institutionalization avoided if a multi-disciplinarv approach is used and the procedure carried out when the patient is psychologically prepared and the objective physiological requirements (ie, vital capacity and negative effort) are fulfilled.

A Comparison of Ventricular Arrhythmia in Coronary Artery Disease Patients Randomized to Surgical and Medical Therapy. •V eil de Soyza; Marvin IHurIJ/zY; Joe Bissett; James Kane, Little Rock

The effect of medical treatment (MT) compared to surgical treatment (S'I') on ventricular arrhythmia (VA) in coronary artery disease (CAD) is unknown. Forty-three patients on MT for at least I yr and 40 patients at least I yr after saphenous vein bypass grafting had 6 h Holter monitoring during a clinic visit without interrupting drug therapy. All were men of similar ages with disabling angina and significant CAD angiographically. Four MT and 10 S'T patients were in functional class I. Graft patency at I yr in 32 ST patients was 90 percent. Significant VA was still present after at least I yr of therapy in ambulatory CAD patients randomized either to M'I' or S'T. Furthermore, no significant differences in VA exists between the two treatment groups. Whereas the overall incidence of PVCS is higher in patients with CAD, PV']" was documented in both patients and controls.

The Sustained Bronchodilating Effect of Terbutaline Aerosol. William E. D()f!,g(~tt; Edward H. Chester; Hugo D. Montrnegro: Howard ]. Schwartz, Cleveland A double-blind crossover study was performed to compare the efficacy of terbutaline with that of metaproterenol. isoproterenol and placebo aerosols. Sixteen asthmatic patients were studied with spirometry and body plethvsmography at frequent intervals during six hours following a single, metered-dose aerosol administration. Heart rate and blood pre&'iure were monitored during these intervals. Statistical significance was determined by analysis of variance. Terbutaline and metaproterenol produced as significant an improvement as isoproterenol in flow rates and airway resistance (Raw) when compared to placebo. Improvement in FEV 1 , FEF200-12()(h and Raw lasted for two hours for all drugs. At five hours, the effect of terbutaline on FEF ~:1-7fi% and FEF;.() was greater (P 0.05) than that of meraproterenol and isoproterenol. No significant change of heart rate or blood pressure as compared to placebo was noted with any of the aerosols. \Ve conclude that all three drugs had an equivalent bronchodilating effect on the large airways that was relatively short acting. Only terbutaline had sustained bronchodilation in measurements of small airways.

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CHEST, 70: 3, SEPTEMBER, 1976

Sterilization of the Fiberoptic Bronchoscope in an Environment of High Bacterial Density. John Donaldson; David Stoop; Susan Williams, Bethesda

The preferred method for decontaminating a fiberoptic bronchoscope is by gas sterilization. This is impractical in a busy practice. Chemical sterilization techniques have not been adequately evaluated in the milieu of high density bacterial contamination. A double-blind study involving Sta ph vlococcus aureus, Streptococcus pyoge1les, Escherichia coli; Klebsiella pnru moniar and Pseudo monas aeruginosa was perfonned. The bronchoscope tip was inserted into liquid bacterial suspensions (Hl1t organisms per ml) which were aspirated through the lumen. The shaft and inner channel were cleansed with each of four antiseptic combinations (120 ml per solution): I) 70 percent isopropyl alcohol/saline; 2) alkaline glutaraldehyde/alcohol/saline; 3) benzalkonium chloride/alcohol/saline, and 4) povidone-iodine/alcohol/saline. Qualitative cultures of previously contaminated external surfaces and quantitative colony counts from a final 10 ml saline rinse were obtained. All combinations were effective in eliminating the organisms or reducing the colony counts (Icr..~ loa organismsj ml) . 'These results suggest that any of the four combinations provides effective decontamination if adequate volumes are used. Pulmonary Manifestations of Late-onset Hypogammaglobulinemia. Russell J. Dukes; Edward C. Rosenow, III; Paul E. Hermans, Rochester, Minnesota

Since respiratory symptoms are the most common presenting complaint of late onset immune deficiency (LID), a review of the records and chest x-ray films of 54 patients with this entity was undertaken to further define the spectrum of respiratory disorders in this disease. Upper or lower respiratory infections were encountered in approximately 90 percent of the patients, Cylindrical bronchiectasis was demonstrated in 21 patients (39 percent) . A thymoma was found in 4 patients (7.4 percent). Two patients were discovered to have diffuse interstitial disease. one with proved lymphocytic interstitial pneumonitis (LIP) and the other with presumed LIP. Of interest were five patients (9 percent) who had no evidence of any puhnonary disease, including one patient with essentially no immunoglobulin and another with known LID for at least 21 years. In patients with severe recurrent infection, an attempt was made to assess the response to therapy.

The Clinical Value and Safety of Graded Exercise Testing Soon after Myocardial Infarction. Laurence Favrot; Sid111~)' C. Smith ; Arlene Niccoli; Homer L. Brammell, Denver

Shorter hospitalization and rapid return to activity after myocardial infarction (MI) has promoted exercise testing (C;Xi') as a guide to rehabilitation. Three hundred fortysix Gx'r on III patients (98M,13F) were obtained within 14 weeks after 120 Ml , 'Three groups were reviewed: A) :; to 42 days after MI (92 eXT); B) 43-63 days (121 cxrj . C) 6498 days (133 GXT). No deaths. repeat MI. or arrhythmias (AR) requiring treatment occurred. Mets increased from 4.0 ± .12 (SEM) in A to 4.8 ± .14 in B, to 5.6 ± .14 in C. Systolic blood pressure and percent maximum heart rate at termination were 148.1 mm Hg ± 2.4 and 69.8 percent ± .87 in A, 1:;6.3 ± 2.3 and 73.7 ± .82 in Band 163.4 ± 2.3 and 78.9 ± .92 in C. Gx'r was usually stopped because of heart rate (61 percent) or symptoms (36 percent) . Most common SYlllPtoms were angina (50 percent). dyspnea (19 percent) and fatigue (14 percent). Abnormal repolarization occurred in

42ND ANNUAL SCIENTIFIC ASSEMBLY 425

16.8 percent of patients. Ventricular AR occurred in 49 percent of patients: 68 percent < 6/min, 22 percent> 6/min, 5 percent paired, 5 percent multifocal. Of 105 rehabilitation efforts, 90 patients were working by 10.5 ± .72 weeks of MI. GXT is safe and useful after MI.

Right Ventricular Contraction Abnormalities in Chronic Coronary Artery Disease: Incidence and Relationship to Prior Myocardial Infarction. Jack Ferlinz; Michael Dell/icario; Richard Gorlin, New York City Left ventricular (LV) contraction abnormalities in coronary artery disease (CAD) are quite common, and have been studied in detail. In comparison, virtually nothing is known about the incidence of right ventricular (RV) asynergy in CAD. The purpose of this study was to evaluate the patterns of RV contractility in normal subjects and in patients with CAD, to determine the frequency of R V wall motion abnormalities when CAD was present, and to establish its relationship to a prior myocardial infarction. Biplane R V cineangiograms were performed on 26 patients. Seven segmental axes of shortening (SAS) were analyzed in each end-systolic and end-diastolic frame, and normalized as percent decrease (or increase) in axis from end-diastolic length. Of 26 patients, eight served as normal (control) subjects (group I), while 18 patients had significant CAD. Of these 18 patients, six had no significant disease of right coronary artery (RCA) (Group 2) while 12 patients had a significant RCA lesion (group 3). Four patients in group 2 had a prior anteroseptal myocardial infarction (ASMI), while six patients in group 3 had a prior inferior myocardial infarction (I MI). There was a progressive decrease in SAS from group I to 2 and to 3. None of the decreases was significant at a P < 0.01 level, however. Only one patient in group 2 exhibited a frank dyskinetic segmental motion of the interventricular septum (patient had a prior ASMI), while two patients in group 3 had a localized dyskinetic segmental motion of the free R V wall (both had prior IMI) . It is concluded that CAD only infrequently produces significant RV asynergy. The dyskinetic motion of the free R V wall is localized and rare, and occurs only in patients with the RCA lesion and a prior IMI. RV damage in chronic CAD therefore does not appear to be of sufficient magnitude to cause significant hemodynamic abnormalities. When such abnormalities are present, they are most frequently due to the significant concomitant LV dysfunction.

Echocardiographic Study of the Acute Hemodynamic Changes Induced by Hemodialysis. Hemal Fernando; Howard S. Friedman; Qa,nar Zaman; Alvaro Celis-Vargas; Emmanuel Masih ; Richard Stein; Anita Yap, Bronx Previous studies of the effect of hemodialysis on cardiac performance have yielded conflicting results. To assess the acute effect of hemodialysis on cardiac performance, 12 echocardiographic studies were performed on patients averaging 44 years of age, who were on maintenance hemodialysis and had no history or ECG evidence of coronary artery disease, asynergy or congestive heart failure. Echocardiography was done in a postabsorptive state immediately before and after four hours of hemodialysis with a Gambro single pass dialyzer. The average weight loss after dialysis was 3.6±0.6 (SE) lbs. Ejection fraction (b.7±1%, P<.()OI), mean rate of circumferential fiher shortening (b.0.27±0.04 citcl sec, P<'()OI), normalized posterior wall velocity (b.O.l7±0.02 sec 1, P < ,(>01) , and normalized interventricular septal veloc-

426 42NO ANNUAL SCIENTIFIC ASSEMBLY

ity (~O.l4±0.03 sect, P<.OOI) increased significantly after dialysis, whereas left ventricular end-diastolic volume (!:::J.II ±2 ml, P<.OOI), mean blood pressure (~6±2mm Hg, P< .05) and systemic resistance (P < .05) declined significantly. There was no significant change in heart rate. Concomitantly, BUN, serum creatinine and potassium declined significantly, whereas bicarbonate and calcium increased significantly. Thus, hemodialysis improves cardiac performance in patients on chronic hemodialysis without apparent coronary artery disease or congestive heart failure. This effect might be explained by the reduction in afterload and / or to an increase in contractility, perhaps attributable to the improvement in serum electrolytes and/or to the removal of a toxic uremic factor.

Vectorcardiographic ST Magni.tude as a Measure of Epicardial ST Elevation and Myocardial Damage in Experimental Acute MI. James M. Foerster; Zakauddin Yera; David Janzen; Dean T. Mason, Davis, Cal. Epicardial ST elevation sum from a grid of electrodes is considered a predictor of the magnitude of myocardial damage. The present study was undertaken to assess the relation between precordial vectorcardiographic (VCG) ST magnitude and epicardial ST elevation sum (EST). Twenty epicardial electrodes on an II mm grid were applied and the thoracotomy closed. After external snare occlusion of a coronary underlying the grid, orthogonal XYZ Frank leads and epicardial leads were recorded every three minutes over two hours during control period and following infusions of isoproterenol, methoxamine, nitroprusside, and during a final reflow period. The VCG ST magnitude was plotted as a function of EST and a least squares straight line approximation was calculated. The r in seven dogs was 0.92, 0.99, 0.95, 0.78, 0.84, 0.93, and 0.97 with a mean of 0.91. Conclusion: VCG ST magnitude accurately reflects the epicardial ST sum during acute ischemic injury. This correlation holds with the use of pharmacologic agents tested and during reflow. VCG ST magnitude is easy to obtain and allows a rapid clinical estimate of acute MI damage and response to interventions.

Oxygen Therapy in Secondary Polycythemia. Larry Foster; Kathryn Corrigan; Allan L. Goldman, Tampa Polycythemia (P) from hypoxemia is an indication for supplemental oxygen (SO). P also occurs in smokers with normal Pa02' but with desaturailon from carboxy-hemoglobin (COHb). P in hypoxemic smokers may respond incompletely to SO because even though hypoxemia is relieved, the COHb may prevent adequate saturation. Sixteen patients with stahle COPD, hematocrit (Hct) ~ 54 percent and Sa02<90 percent were studied. Smokers were encouraged to quit; two stopped and reversed their polycythemia. Fourteen patients were placed on continuous low flow so. Three nonsmokers who used SO inadequately (for less than six hours a day) failed to respond. The Pa02 of the groups were not different (P>.49) and were higher on SO (P<.OI). The COHb and Hct were higher in the smokers before and after SO (P<.OI). Both groups responded to so with an increase of 5a02 and decrease of Hct (P < .01) , but the changes were less dramatic in the smokers in spite of comparable increases in Pa02. Conclusions: I) nonresponse may be due to noncompliance in using SO; 2) hypoxic smokers with P may respond to discontinuing smoking and not require SO; and 3) continued smoking may cause an incomplete response to SO.

CHEST, 70: 3, SEPTEMBER, 1976

Evaluation of Ventilation and Perfusion Changes in Anesthetized Dogs following Saline Lobar Lavage. Richard A. Francoz; Ronald Konopka; Vincent Sgroi; Bernard B. Brach; Kenneth M. Moser, San Diego The therapeutic application of endobronchial lavage has been inhibited hv concern regarding alterations in gas exchange, particularly hypoxemia. However, the sequence of post-lavage gas exchange alterations, and attendant ~ /Q disturbances, is not well defined. To define this sequence, we studied ten mongrel dogs following lohar lavage with approximately R5 Inl/kg of saline solution via a fiberoptic bronchoscope. Sequential v and Q scintiphotography ( 133 xeno n ) and arterial blood gas measurements were performed. Computer linkage to the scintillation camera allowed quantification of V and Q data fro In the lobar area of interest. T'he data indicated the following: lavage induced a reduction of lobar ~ and Q in all dogs. The reductions usually were present immediately post-lavage, began to clear as early as one hour, and cleared completely by six hours postlavage. Significant drops in computed lobar ~ /Q relationships did not occur. Wh ile hypoxemia did occur immediately post-lavage, it was mild and transient.

Transthoracic Needle Biopsy. Willard A. Fry, P. Manalo, Evanston, Illinois Transthoracic needle biopsy by fine needle aspiration of peripheral pulmonary lesions is being recognized as the most accurate means of diagnosing lung tumors beyond the reach of the bronchoscope. I t deserves more acceptance and use in America, because it is easily performed and traditional fears of seeding the needle tract with tumor cells have not been substantiated by critical analysis of results. In our series of over 60 patients, our accuracy in tumor diagnosis is in the 90 percent range for both primary and metastatic lesions. There has been no mortality and no seeding of the needle tract with tumor cells. Some patients experienced temporary streaking, but none experienced pulmonary hemorrhage. The incidence of pneumothorax is 30 percent, hut most patients do not require pleural intubation. The procedure is performed under local anesthesia with a long 2'2-KauKe needle, a 20 ml disposable syringe, and a special aspirating handle (Cameco pistol) under fluoroscopic control. A biplane fluoroscopic set-up is not essential. The aspirated material is "blown" out of the needle, and smears are prepared by both the Papanicolaou and Giemsa techniques, as they are complementary in the cytologic diagnosis of lung tumors. The accuracy of this technique in lung tumor diagnosis far exceeds that of all other standard diagnostic measures. 'Ve feel that it is particularly important for poor risk patients who are, nonetheless, candidates for thoracotomy if the lesion is known to he malignant, and for patients in whom certain tumor diagnosis is essential before the institution of chemotherapy or radiotherapy. It is a procedure which should be available and easily performed in every full service hospital in this country. It does not require complicated equipment or technique.

The Effects of Diuretic Induced Metabolic Alkalosis on Respiratory Center Sensitivity (RCS) in Decompensated Cor Pulmonale. (;eo/lre)' Cordon; J. Eugene Millen; Frederick L. Glauser, Long Beach We have observed that patients with decompensated cor pulmonale may experience an elevation in their PaC0 2 (with-

CHEST, 70: 3, SEPTEMBER, 1976

out a change in pH) following vigorous diuresis and weight loss. 'Ve hypothesized that a diuretic-induced alkalosis led to transient RCS depression. 1'0 test this theory we studied ten cor pulmonale patients receiving diuretics during ten episodes of increasing failure employing P U. l (inspiratory pressure 100 nlSCC after onset of occlusion) as an index of RCS. When stable the patients' mean PaC():! was 52.3 ± 2.fi mm Hg. HCO;l: 31.1 ± 3.1 mf.qz l.; pH: 7.37 ± 0.06. During decompensation. PaC():! increased to :)9 ± H.2, HC()~ to 35 ± 3.9, pH to 7.3H ± 0.07. Employing correlation coefficients and regression analysis the following relationship existed (40 separate measurements): PO. l to HCO:r r == 0.47, (P 0.01); P O. l to PaCO:!: r == 0.15, ns, Po 1 to pH: r == -0.14, ns. 'Ve conclude that in acutely decompensated cor pulmonale patients, an increase in HC0::l (induced by diuretics) can decrease RCS leading to an increase in PaC().) without a change in pH. -

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Systemic Air Embolism following Penetrating Lung Injuries. joseph ill. Grah am ; Arthur C. Beall, [r.; G. Dennis Vaughan; Kenneth L. Mattox, Houston Although systemic air embolism has been reported in association with penetrating lung injury, such occurrence recently has been questioned. Results of animal experiments designed to elucidate this phenomenon have heen at variance. Design of such experiments, however, has not alwavs simulated the clinical setting. Intratracheal pressure was me~sured in 12 patients undergoing emergency thoracotomy for resuscitation following trauma, and exceedingly high pres..~ures were found. Six dogs then underwent thoracotomy and a penetrating lung injury was produced. Intratracheal pressures similar to those observed in the clinical situation were applied, and in each animal air was seen in the coronary arteries within five minutes. These results strongly suggest that systemic air embolism can occur during thoracotomy for resuscitation following penetrating lung injury unless certain precautions arc observed. When a hand ventilatory bag is used for positive endotracheal respiration, a pressure monitor should be included in the system.

Effects of Aortic Balloon Pumping During Cardiopulmonary Bypass on Myocardial Perfusion, Metabolism, and Contractility. Frederick L. Graver; [oh n G. Fetoel; [oseph Vinas: [olin J" Ghidoni; Kit V. Arom ; J. Kent Trinkle, San Antonio Pulsatile flow during cardiopulmonary bypass produced by an intraaortic balloon pUlnp has been advocated to improve intraoperative myocardial perfusion and metabolism. Total cardiopulmonary bypass was instituted for one hour in 32 dogs. Coronary sinus lactate and pyruvate, and myocardial lactate and ATP were measured before, during and for one hour after bypass. Myocardial blood flow was sequentially measured by the radioactive microspherc technique. Balloon pumping was initiated after obtaining the 10' data and continued for the remainder of bypass. The animals were divided into five groups: group I-control, beating heart; group 2balloon pump, beating heart, bypass inflow via femoral artery; group 3-balloon punlp, heating heart, bypass inflow via aorta; group 4-control, ventricular fihrillation; J.,Troup !)balloon pUlnp, ventricular fibrillation. No statistically significant differences between groups were found. It is concluded that intraaortic balloon pumping during cardiopultnonary bypass does not improve myocardial perfusion or nu-t.rhol ism.

42NO ANNUAL SCIENTIFIC ASSEMBLY 427

The Bronchoscopic Application of Helium. Susan Harris; Roger Bone; William Ruth, Kansas City, Kansas Reports have demonstrated that when fiberoptic bronchoscopy (FB) is done on patients intubated with endotracheal tubes smaller than 8.0 mm there is critical rise in airways resistance with resultant inadequate ventilation. The purpose of this study was to demonstrate in a laboratory mechanical analogue and subsequently in intubated patients that by use of a 70 percent helium-30 percent oxygen mixture (0.55 density) as the ventilating gas instead of a 70 percent airSO percent oxygen mixture (1.304 density) there was significant decrease in the airway resistance (RAW) with the low density gas. In the analogue the decrease in RAW using low density gas was 50 ± 7 to 26 ± 4 percent (mean ± standard error) with endotracheal tubes varying from 7 to 9 mm in size. Our observations demonstrate that use of a low density helium-oxygen mixture during the time of FB may allow the procedure to be done with smaller endotracheal tubes than previously considered safe and may obviate the need to reintubate the patient with a larger tube prior to the procedure. Diagnosis of Atypical Esophageal and Cardiac Pain. Robert D. Henderson; Douglas E. Wigle; Karen Sample, Toronto One hundred five patients were studied with chest pain which was considered atypical because of distribution, precipitating or relieving factors, and presented as a diagnostic problem. Each patient was investigated by esophagogram, manometry and acid perfusion, as well as exercise ECG andj or coronary angiogram. Forty-three were diagnosed as having esophageal pain because of a positive acid perfusion test, together with radiologic or manometric evidence of esophageal disease; 12 were diagnosed as cardiac because of positive exercise and/or angiographic narrowing greater than 70 percent in one or more arteries, together with negative acid perfusion; 21 had both cardiac and esophageal disease, and in 29 no diagnosis was made. Sixteen with esophageal disease were effectively treated by hiatal hernia repair. Esophageal pain induced by exercise, radiating to the ann and hand, or relieved by nitroglycerin is easily confused with cardiac disease. The incidence of these symptoms and the reliability of the evaluation methods are described. Aspiration and Gastroesophageal Reflux. Robert D. Henderson, Colin R. Woolf, Toronto Aspiration in patients with gastroesophageal reflux may cause respiratory disease. The frequency mechanisms involved and incidence of respiratory symptoms are undetermined. One thousand consecutive refluxing patients were studied by history, radiology, manometry and where indicated pulmonary function tests to determine the incidence of aspiration, mechanisms involved and their respiratory effects. Reflux and gastric aspiration occurred at night while aspiration of food and saliva occurred during swallowing from cricopharyngeal obstruction and forward spillage. Two hundred sixty-four patients aspirated, 124 without respiratory symptoms, 89 with laryngeal symptoms, 15 with bronchitis, 2 with bronchiectasis and 34 with asthma. Night aspiration produced respiratory symptoms in 69.5 percent and cricopharyngeal dysphagia and aspiration in S9.7 percent. Obstruction at the cricopharyngeus is shown to be secondary to motor incoordination. This symptom together with reflux aspiration has been corrected by hernia repair in 128 patients. Respiratory symptoms of cough,

428 42ND ANNUAl SCIENTIFIC ASSEMBLY

recurrent infection and bronchiectasis are improved, but improvement by history and pulmonary function studies in the asthmatic patient is unpredictable. Management of Coarctation of the Aorta in Infancy. Virginia M . Herrmann; Hillel Laks; Leonard Fagan; David T'erschluse; Vallee L. Willman, St. Louis Twenty-six infants under one year (mean 12.4 weeks, 4.1 kg) underwent coarctation repair. Eight had ventricular septal defect (VSD) , three transposition of the great arteries with VSD and five had severe tubular hypoplasia. One required mitral valve replacement and one repair of total anomalous pulmonary venous return. Fifteen had repair by primary anastomosis. Eight underwent Dacron or subclavian aortoplasty. Three required bypass grafts. Eighteen survived the operation. Mortality for repair with simultaneous pulmonary artery banding was high accounting for seven of eight early deaths. For coarctation with VSD, we recommend repair without banding followed by VSD closure if indicated. Three patients have been treated successfully in this manner. Eighteen were followed-up a mean of 48 months with three late deaths. Of the 13 survivors with preoperative hypertension, seven have persistent hypertension, and four have a gradient between upper and lower extremities. The advantages and technique of aortoplasty will be discussed. Inhalation of Triamcinolone Acetonide Via IPPB or Compressor Pump Therapy. John E. Hodgkin; Richard H. Guth; Jerald C. Nelson, Lorna Linda, Cal. Inhalation of triamcinolone, using cartridge-inhalers, has been reported to provide symptomatic benefit in asthmatics while avoiding systemic side-effects. Since the inhalers are not commercially available here, we studied the effect of 2 or 3 mg of injectable triamcinolone aerosolized bid to qid along with a bronchodilator/saline solution using an IPPB device or a compressor pump. This regimen has been used in 90 patients with obstructive airway disease allowing the majority to avoid or withdraw oral corticosteroids, or to tolerate alternate-day dosage. To test for pituitary-adrenal suppression, 12 patients on daily steroid aerosol for 1.5-14 months (mean 8) but not receiving oral steroids underwent insulin-induced hypoglycemia studies. The serum cortisol rise (peaks 17-32 fJ.gj 100 ml; mean 23) and serum HGH rise (peaks II-56 ngjml; mean 33) were not significantly different (P .05) from untreated controls. Despite prolonged adrenal steroid therapy by this route, there was no evidence of adrenal or pituitary suppression.

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Review of 190 Cases using the Intra-Aortic Balloon Pump. James F. Hoffman, Jr.; Kenneth L. Kayser; Richard T. Shore; W. Dudley Johnson, Milwaukee The intra-aortic balloon pump has become an accepted and extremely important adjunct to the critically ill patient. It is usually used in cardiac patients, but occasionally is used in septic, bum, and other critically ill patients. From June, 1971, through April, 1976, we have used the IABP in 190 cases. Elective cardiac cases comprised 134 with 95 (71 percent) surviving. These can be divided into 32 known poor risk cases in which the IABP was inserted during or prior to surgery, and 102 in which the IABP was used after surgery was completed and the patient could not be successfully taken off cardiopulmonary bypass. Twenty-two patients undergoing emergency cardiac surgery required the use of the

CHEST, 70: 3, SEPTEMBER, 1976

IABP with 50 percent survival. Twenty-five patients in severe cardiac distress not undergoing cardiac surgery had the IABP inserted; 32 percent were successful. Included for completeness are eight patients with burns and one patient with septic shock who were balloon pumped. There were no survivors. These 190 cases will be discussed in detail by groups and further divided into the years 1971 through 1976. The use of the IABP at the right time and correctly is an invaluable cardiac surgical adjunct.

Radioisotope Scanning in the Initial Staging of Bronchogenic Carcinoma. Robert G. Hooper; Cash R. Beechler; Merrill C. Johnson, Washington, D.C. The use of radioisotope scans (liver, brain, and bone) for the detection of possible metastatic disease was studied and compared to clinical evalution (history, physical exam, and laboratory screening tests) in patients undergoing initial work-up for carcinoma of the lung. A total of 173 patients (130 retrospective and 43 prospective) underwent 161 liver, 138 brain, and 102 bone scans using standard techniques. Patients were grouped according to the radiographic stage of disease using the admission chest roentgenogram. The clinical findings were compared with the scan results. Patients (30) with radiographic stage disease and no clinical evidence of spread had no positive scans (0/67). Patients (33) with radiographic stage I disease and clinical evidence of spread had 17.7 percent positive scans (14/79). Eighty-five patients with radiographic stage 2 and 3 disease had clinical evidence of spread and 23.8 percent positive scans (46/193). The patients (26) with stage 2 and 3 disease without clinical evidence of spread had 1.6 percent positive scans (1/61). The clinical evaluation of patients with carcinoma of the lung is as sensitive as routine radioisotope scanning in screening for metastases.

Seasonal Variation of Thoracic Airway Obstruction in Allergic Rhinitis. David W. Howard; William E. Doggett; Adi A. Gerblich ; Edward H. Chester; Howard J. Schwartz; Michael J. Belman, Cleveland We have previously documented airway abnormalities during pollen season in subjects with allergic rhinitis. To determine whether these abnormalities persist out of season, 17 of the same subjects were studied with body plethysmography, spirometry, maximum expiratory flow volume curves breathing air and a helium-oxygen mixture, and methacholine inhalation challenge. Ten of the 17 had elevated specific airway resistance (SRaw) during pollen season, mean 5.74 ± 1.79, compared to 3 of 17 with increased SRaw out of season, mean 4.19 ± 1.36, (P 0.005) . There was no significant difference between mean values for FEF 25-7!)%' FEV l' or volume of isoflow determined in and out of pollen season. Thirteen of the 17 subjects demonstrated hyperreactive airways with methacholine challenge. We conclude that intrathoracic airways in allergic rhinitis are abnormal in the majority of patients during pollen season. Measurements of SRaw rather than FEF :!!)-i!i%' FEV i: or volume of isoftow detects this alteration. This abnormality reverses out of season, although the majority of subjects continue to demonstrate hyperreactive airways.

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Echocardiographic Diagnosis of Calcified Mitral Anulus. Paul F. Howard; Sergio V. Cabizuca; Alberto Benchimol; Kenneth B. Desser; Connie Sheasby, Phoenix Six

women, ages

75-80

(x==78)

CHEST, 70: 3, SEPTEMBER, 1976

years

presented

with

pansystolic apical murmurs. Standard two-view chest roentgenograms demonstrated calcification of the mitral anulus (CMA) in only one suhject. The patients underwent echocardiography (lJCG) with a 2.25 MHz transducer focused at 7.5 cm. All subjects manifested the abrupt appearance of dense heavy echoes emanating from the posterior MA during an lJC(; scan from the aortic root to the left ventricle. These echoes extended into the left ventricular midcavity to the region of the papillary muscles. Densest echoes were contiguous with the posterior mitral valve leaflet. Fluoroscopic image intensification demonstrated a "C" or ")" CMA in all patients. One subject developed complete heart block and another had large echo-free spaces anteriorly and posteriorly. Pericardiocentesis in this latter patient resulted in the removal of 800 ml of intrapericardial fluid. CMA may result in UCG findings that superficially resemble those of pericardial effusion (PEFF) and careful analysis of the UCG sweep must be accomplished to identify posterior left ventricular endocardial and pericardial structures. Coexisting CMA and PEFF can, however, be diagnosed by UCG. It is concluded that UCG represents a valuable method for the noninvasive diagnosis of CMA.

Does Tobacco Smoke Impair Alveolar Macrophage Function? Gary L. Huber, John Shea, Boston The question of the health effects of cigarette consumption, shrouded in controversy and partial truths since its inception, deserves definitive clarification. In an attempt to establish direct causal relationships between tobacco and lung disease, the in uitro effect of smoke on alveolar macrophages (AM) bactericidal function has been extensively studied by many investigators. Publications on AM function from human smokers and from experimental anirnals, however, have been paradoxically contradictory, with results ranging from totally impaired AM function to no impairment or even enhanced function reported. To investigate this problem, studies were performed comparing in vitro exposure of AM to tobacco smoke versus in vitro function after in vivo exposure. Rat AM were harvested from nonsrnoked animals by pulmonary lavage and in vitro bactericidal inactivation of S albus quantified. Control AM inactivated 74.8 percent of the bacteria after three hours of incubation. Exposure in vitro to 2, 4, 6 and 8 ml of whole smoke impaired bacterial inactivation to 50.4. 37.4,22.6 and 17.7 percent, respectively, with differential filtration revealing that the AM cytotoxin was a highly water-soluble component of the gas-phase of the smoke, However, AM harvested from animals acutely exposed in vivo to progressively increasing doses of tobacco smoke had no impairment in vitro of bactericidal activity, even when the in vivo tobacco exposures were at a near lethal level. Analysis of tobacco gas-phase components indicated that because of their very high water solubility the AM cytotoxins reach an unrealistically high concentration when added to in vitro systcms. Conversely, data generated from lun~ ana log analysis indicated that when tobacco smoke is inhaled the wet airways of man selectively remove these cytotoxins and reduce the concentration of these gas-phase components at the alveolus to levels not detectably toxic to AM. Thus, the adding of whole tobacco smoke or smoke components to AM in in vitro bactericidal systems does not provide a realistic bioassay. The selective absorption of water soluble cytotoxins in these systems to concentrations five logs or higher than in the lungs of man Inay provide an explanation of the paradoxic results reported to date.

42NO ANNUAL SCIENTIFIC ASSEMBLY 429

Oxygenation during Chest Physiotherapy. Jon Huseby; Leon(Jf(1 l l u dson : Katlirvn Stark; Martha Tyler, Seattle

Postural drainage and chest percussion are physiotherapy measures used in patients with retained secretions or decreased ahilitv to cough. Because several patients developed arrhythmias. including ventricular tachycardia, during chest physiotherapy, a study was initiated to look at oxygenation during the procedure. Arterial blood gas levels were obtained at baseline, in each drainage position, and 30 minutes after procedure. Of 17 patients studied, the Pa02 decreased an average of 19.4 111111 Hg. In nine patients, Sa02 decreased 3 to 15 percentage points. Five of these patients were in a position with the 1110st diseased lung down. Three increased their PaC0 2 but this only partially accounted for the decreased Pa02' T'he decreased arterial saturation during physiotherapy n1ay be due to increased shunt or V IQ abnormality, especially if the diseased lung is down. The effect of a possible decrease in cardiac output has not been evaluated. Supplementary oxygen during physiotherapy may be indicated if oxygenation is borderline.

Angina Pectoris and Coronary Atherosclerosis in Patients with Mitral Stenosis. Tetsuo Ishimori; Fred A. Heupler; Earl K. Shire)'; William C. Sheldon, Cleveland The pathophysiology of chest pain in patients with mitral stenosis (MS) remains uncertain, and the incidence of coexisting coronary atherosclerosis (CAS) is believed to be low. One hundred sixty-nine patients with predominant MS and no aortic valve disease were evaluated for the presence of significant CAS and chest pain. Group A included all patients with typical angina pectoris (AP). Group B included those with no angina. CAS was considered significant where there 'Was !i0 percen t or more narrowing of a t least one major coronary artery. The female.male ratio was 2.5: I. Twentythree percent (39/169) of all patients had typical angina. Significant CAS was present in 16 percent (27/169): 28 percent (11/39) in group A and 12 percent (16/130) in group B, P

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Thus, significant CAS is not infrequent in MS, especially those with AP and may account for the chest pain syndrome. HOWe\Tr, the mechanism underlying AP in patients with MS and no CAS cannot be determined from this investigation and deserves further study.

Comprehensive Management of Patients with Left Main Coronary Disease. Ellis L. Jones; John S. Douglas; Joel A. Kaplan: Spencer R. King, Ill; Charles R. Hatcher, lr.. Atlanta Previous reports have stressed the increased morbidity and mortality in patients with left main coronary disease (LMCD) dur ing catheterization and surgery. To avoid this increased morbidity and mortality, the catheterization, anesthetic and surgical management must be different from that used in most patients with CAD. Experience with 137 patients and Ll\1CD of 70 percent stenosis was reviewed. Catheterization mortality was 2 percent using a special single catheter, femoral percutaneous technique. Stable anesthetic induction was provided by reducing myocardial O 2 demand with IV nitroglycerine during episodes of hypertension and avoidance of tachycardia by continuing propranolol until the night prior to surgery. Sixty-six patients have undergone myocardial revascularization (MR) with a 7.5 percent hospital mortality. There have been three late deaths (4.1 percent). Criteria for selection of patients with LMCD undergoing MR and long-

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430 42NO ANNUAL SCIENTIFIC ASSEMBLY

term results of operated and unoperated patients will be discussed with regard to LV function, extent of CAD, previous AMI and anginal pattern. Special techniques in ECG and hemodynamic monitoring and indications for use of the intra-aortic balloon in patients undergoing MR with LMCD will be discussed.

Bronchial Carcinoids: 15 Years' Follow-Up. Jean Guy Joseph; Andrew Churg; Tom R. DeMeester; David B. Skinner, Chicago The natural history of bronchial carcinoid tumors has been debated, with some authors finding in excess of 90 percent five-year survival, while others report only 50-60 percent five-year survival. Longer term follow-up studies in excess of 15 years are nonexistent. Histologic classification and patient status were reviewed for all patients with a diagnosis of bronchial carcinoid at the University of Chicago Hospital prior to 1960. Twelve such patients were found. There were five men and seven women, with an age range of 17 to 70, and a mean of 34.5. All patients presented with cough associated with recurrent respiratory infection in eight and hemoptysis in eight. All tumors were in a main or lobe bronchus. All were treated by surgical excision (six pneumonectomies, two bilobectomies, and four lobectomies). All tumors involved the bronchial cartilages and seven extended into adjacent lung parenchyma. Tumor sizes ranged from I to 4.5 em, but size did not correlate with the presence of metastasis. Three patients had hilar lymph nodes involved and two of these had distant metastases, dying 3.1 and 5.7 years after surgery from widespread disease. The third one is still living 32.6 years after surgery without recurrent disease. Of nine patients with no lymph node involvement, two died from nonrelated causes 12.7 and 23 years after surgical treatment. The remaining seven patients are living with no recurrence 15 to 27 years post surgery (five of them more than 22 years). The overall 15 year survival (corrected for tumor related deaths only) was 83 percent.

Abstinence from Smoking: Effect on Pulmonary Deposition and Mucociliary Clearance of Inhaled Particles. Bharat V. Joshi, Peter Werner, Chicago In smokers, reversibility of small airways obstruction has been documented after cessation of smoking. Since mucociliary clearance (MCC) was found abnormal in smokers, we reasoned that cessation of smoking might also normalize impaired MCC. Thirteen former (years quit == 1.9), eight current, and nine nonsmokers, all age matched, were studied. Pulmonary function tests included flow rates at low lung volumes. Pulmonary deposition and MCC of labeled monodisperse iron oxide particles was measured with a scintillation camera. Current smokers did not smoke for at least two hours prior to the study. Pulmonary function tests were normal and not significantly different between the three groups. Deposition of particles was uniform throughout both lung fields in all subjects. MeC was faster in former smokers (Tso == 3.8 b ± 0.6 SD) when compared to current smokers (T:. o == 4.3 b ± 0.6) but was significantly slower (P 0.01) than in non-smokers (Tr.o == 1.6b ± 0.3). These data suggest improvement but not complete normalization of Mec after abstinence from smoking and question the easy reversibility of smoking induced damage to the airways.

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CHEST, 70: 3, SEPTEMBER, 1976

Myocardial Revascularization in Patients with Severe Coronary Artery Disease and Marked Impairment of Left Ventricular Function. Jerome Harold Kay; Pablo Zubiate; A. Michael Mendez., Los Angeles A total of 304 bypass grafts were performed in 140 patients with an ejection fraction (EF) 0.2 or less (normal 0.70) . Age ranged from 27 to 76. Angina was present in 134 patients; 102 were in New York Heart Association class 3 and 38 in class 4. There were 31 hospital deaths (22 percent). There were five hospital deaths in the last 57 consecutive operations (9 percent) . At postoperative studies 3 to 49 months (mean 17) following surgery, 80 of 89 grafts (90 percent) were patent. Average increase in EF was from preoperative 0.16 to postoperative 0.25, P 0.001. Left ventricular end-diastolic pressure decreased an average of 7.4, P 0.01. Of the 83 living patients, 79 are improved with regard to physical activity and angina. Seventy-nine patients were followed medically with 62 deaths, a survivability of 22 percent at five years. Of the patients operated upon, actuarial studies revealed 59 percent survivability at six years. Surgery is advised for patients with an ejection fraction of 0.2 or less.

Left Ventricular Function During Airways Obstruction in Normal Subjects. Anthony Kerigan, David H. Spodick, Boston Six normal men were studied to define the changes that occur acutely in left ventricular function during simulated expiratory obstruction. Measurements were made in milliseconds of pre-ejection period (PEP), left ventricular ejection time (LVET) and rate corrected LVET as ejection time index (ETI). Blood pressure, including the presence of pulsus paradoxus (PP) , was recorded. Three subjects developed PP. This group was characterized by greater respiratory changes in both ETI (6=46) and PEP (6=14) than those without PP (6ETI=12, 6PEP=6). The direction of change remained that seen in nonresistance breathing. In addition, the PP group showed greater increase in systolic pressure during resistance (22 mm Hg) than those without PP (9 mm Hg). Changes seen during resistance breathing were due mainly to decrease in inspiratory ETI and increase in inspiratory PEP. These results suggest marked alterations in left ventricular filling during inspiration in the presence of pulsus paradoxus.

Cuff/Trachea Ratio as an Indicator of Tracheal Damage. Earoque Khan; Narayan C. Reddy; Aria Khan, Jamaica, New York A prospective study froin July, 1974 to December, 1975 was conducted in 135 intubated adult patients who had cuffed intratracheal tubes for more than two days. Tracheal lumen diameter at the level of the clavicle was measured and the inflated cuff transverse diameter measurements around the endotracheal tube or tracheostomy were made daily on the portable bedside chest x-ray film in all 135 patients. The "ratio of these two we refer to as the cuff/tracheal or CIT ratio. Of the 115 patients with CIT less than 150 percent, 85 survivors developed no clinical evidence of tracheal stenosis or fistula. Of the 30 patients who died, 15 were autopsied and none had evidence of exposed tracheal cartilage at the cuff site. Of the 20 patients with CIT greater than 150 percent, nine died, four were autopsied, and all four showed severe tracheal mucosal damage with exposed cartilage at the cuff site. Of the remaining 11 patients, three returned with symptomatic tracheal stenosis two weeks, four months and one year after

CHEST, 70: 3, SEPTEMBER, 1976

removal of the intratracheal tube. These three patients had CIT ratios of 156, 200 and 210 percent respectively during the

course of their acute respiratory failure. All three required tracheal resection and reanastomosis. The remaining eight patients are currently being followed-up and evaluated for tracheal stenosis. In retrospective analysis of our previous cases of tracheal stenosis (three) and tracheoesophageal fistula (four) seen in the preceding four years, all showed a CIT ratio above 150 percent with a mean ratio of 225 percent. We conclude that a CIT ratio greater than 150 percent is indicative of severe tracheal damage. Such patients are at a very high risk of developing tracheal stenosis or fistula at the cuff site. Some comments as to prevention of this complication will be presented.

Stress Ulcer Bleeding as a Major Cause of Death in Patients Undergoing Treatment for Acute Respiratory Failure. Faroque Khan, Nathan S. Serif], Jamaica, New York Analysis of eight years' experience at our institution with the management of acute respiratory failure (AF) in over 1,()()() patients in our respiratory intensive care unit (RICU) has demonstrated that rather than ventilatory problems, the complication of massive upper GI hemorrhage from stress ulcers has emerged as the leading cause of death. Although upper GI bleeding has been noted in approximately one quarter of our RICU patients, a recent 12-month prospective study revealed that 19 of our 211 RICU admissions bled severely enough to require transfusions of two or more units of blood. The mortality in this group of patients was an alarming 55 percent, compared to our overall RICU mortality of 16 percent. The precise etiology of stress ulcer bleeding in ARF is unknown. Our attempts at prevention in the last three years with the routine use of nasogastric suer ion and hourly antacids, have, in our noncontrolled experience, been obviously inadequate. Diagnosis is best confirmed by endoscopic visualization. Prompt treatment of massive u nr ontrollable bleeding with blood transfusions and pitressin infusion into the coeliac axis using a constant infusion pHlllp has become standard therapy in our unit in that it has almost eliminated the need for surgery in the last 18 mouths, and appears to lessen the danger of hypotension and result inK acute renal failure. When the latter complication dc\ clops. survival is rarely seen. Laboratory and cooperative cliu ii a I studies and pathogenesis, prevention and management of stress ulcer bleeding in ARF are strongly urged.

Effect of Therapeutic Concentrations of Theophylline.' 011 Calcium Exchange in Tracheal Rings. Ralph C. Kolbrrk: William A. Speir, [r.; W. Robert Grabenkort.: Edwin 1). Bransome, Jr., Augusta, Georgia A number of investigators have suggested that inhibition of cyclic nucleotide phosphodiesterase is the mechanism of action of theophylline (Theo) bronchodilators. Increased intracellular levels of cyclic 3',5' adenosinemonophosphate «("AM P) have been found in tracheal rings in studies utilizing high concentrations of Theo (usually 1 millimole) which arc toxic in vivo. A careful analysis of the relationship between thcrapeutic concentrations of Theo (5-20 p.g/ml) and cAM P accumulation was needed. Guinea pig tracheal rings were incubated (n= 10 to 20) for 6 minutes in solutions containing Theo concentrations of 5, 10, 12.5, 15, 20 and 200 J.LK/Illi. cAMP levels for each incubation were 12.6 ± 2.3, 14.4 ± 1.3, 18.4 ± 2.8, 16.6 ± 2.2, 18.0 ± lA, and 20.4 ± 2.7. picomoles per milligram of protein (pmol/rng protein) respcctivelv.

42NO ANNUAL SCIENTIFIC ASSEMBLY 431

None of the values in the therapeutic range was statistically different from the control value of 14.4 ± 1.9 pmolj mg protein. On the other hand, therapeutic concentrations of Theo exerted a profound stimulatory effect on 45calcium (45Ca) uptake. Theo concentrations of 0, 2.5, 5, 12.5, 20 and 200 p.g/ml resulted in tissue/bath 45Ca ratios of 8.37 ± 1.05, 8.60 ± 1.42, 15.11 ± LIS, 17.67 ± 1.S9, 18.86 ± 1.S8 and 19.55 ± 1.91 percent respectively. Thus, calcium exchange rates were substantially elevated at Theo concentrations which exerted no measurable effect on tissue cAM P levels. The results of our study show that further investigations of the mechanism of action of Theo bronchodilators are indicated. Familial Prevalence and Genetic Characteristics in Chronic Obstructive Pulmonary Disease. F. Kueppers; R. Drew Miller; H. Gordon; Norman G. Hepper; K. Offord, Rochester, Minnesota Documented search for COPD or chronic bronchitis in 1,441 parents and siblings of 111 index cases and III matched controls revealed twice the frequency of disease among siblings of index subjects, but not among parents. Measurement of pulmonary function in closest sibling of the same sex available for study confirmed the higher frequency of COPD reported by probands on family questionnaire. Comparison of reported vs measured involvement in each closest sibling showed more frequent false negative reporting by index than control probands, a phenomenon different than expected. Analysis of the distribution of sibship size and frequency of airway disease in relation to size showed no family clustering that would inflate the prevalence of the disease in the index group. There were 3 PiZ alphaj-antitrypsin phenotypes among the index cases, but none among the controls. Nine MZ pi phenotypes were seen in the index grou p and six among controls. Both of these frequencies are greater than found in the general population. The occurrence of the Z or MZ phenotypes does not explain the entire difference of frequency of COPD in the two groups of families. Other genetic or environmental factors appear to be also at play which account for the underlying difference in prevalence in the two groups of siblings. The Effect of Aminophylline on Ventilatory Responses in Normal Man. S. Lakshminarayan; Steven A. Sahn; John Y Weil, Denver

The effect of aminophylline infusion on hypoxic and hypercapnic ventilatory responses (HVR and HCVR) was studied in six normal subjects. Isocapneic HVR was measured by monitoring end-tidal oxygen and carbon dioxide tensions (PA02' PAC0 2) and minute ventilation (VE) while 100 percent nitrogen was added to inspired gas to produce a gradual decrease in PA02 from 120 to 40 mm Hg. HVR was measured as the shape parameter A, of the VE-PA02 curves, such that the higher the value of A, the greater the HVR. Following intravenous aminophylline (5mg/kg body weight) a significant increase of A was noted (P 0.05). HCVR was measured as the slope S of the VE/C0 2 line. No increase was noted in S and the point of intercept, B, following aminophylline (P 0.05) . The mean serum theophylline level 30 min, following infusion was 9.41 JLg/ ml. There was a statistically significant increase in O 2 uptake (Vo 2) and CO 2 production (Vco2) following aminophylline. Spirometry showed no change following the infusion. The data suggest that pharmacologic doses of aminophylline augment hypoxic ventilatory responses.

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432 42ND ANNUAL SCIENnFIC ASSEMBLY

Usefulness of Air and Helium Flow-Volume Curves in the Evaluation of Upper Airways Obstruction. Thomas F. Lavelle, tr.. Harold H. Rotman; John G. Weg, Ann Arbor We evaluated the ability of air and helium flow-volume curves to distinguish upper airways obstruction (U AO) from the diffuse peripheral airways obstruction of chronic obstructive pulmonary disease (COPD). We determined the percent increase in the peak expiratory flow rate (PEFR) and maximum flow at 75 percent, 50 percent, and 25 percent of vital capacity during helium breathing as compared to air breathing (~PEFR, ~ Vmax75, ~ Vmax50, ~ Vmax25) in five normal subjects and three patients with COPD while breathing through fixed resistances and in six patients with tracheal obstruction. In normals, the helium response (~V) at all four points remained normal and unchanged from baseline until the simulated obstruction was severe (6 mm orifice) when all of the ~ V's increased by over 50 percent. The COPD patients maintained their low baseline ~ V's until the obstruction was severe (6 mm orifice) when only their ~PEFR, ~ ~max75, ~ Vmax50 increased by over 50 percent. Five of the six patients with U AO had ~ Vs very similar to the normal subjects with similar degrees of simulated obstruction, and the one patient with concomitant airways obstruction extending below the carina had very low ~ Vs at each point. We conclude that U AO can be identified by high ~ Vs and that severe UAO can be identified even in the presence of more peripheral airways obstruction by a normal ~ V at high lung volumes (normal ~PEFR, ~ Vmax75).

Coronary Artery Bypass Surgery at the Extremes of Age. Gerald M. Lawrie; George C. Morris, [r.; Michael J. Murray; Don. W. Chapman, Houston Surgery has been performed for angina pectoris in 110 patients age 21-40 years « 40 group) and 170 patients age 65-81 years. The 40 group comprised 97 men and 13 women. Mortality (30 day) was 0.9 percent. Mean hospital stay was 9.5 days. Follow-up at 3-67 months showed excellent relief of angina in 88 patients and improvement in 12. Graft patency in 25 patients (37 grafts) was 87 percent. In the 65 group, there were 128 men and 42 women. Mortality was 12.8 percent. Mean hospital stay was IS.S days. Follow-up at 4-52 months showed excellent relief in 133 patients and improvement in 13 patients. Graft patency in 20 patients with 31 grafts was 89 percent. Thus, despite a high incidence of significant metabolic problems such as diabetes mellitus and hyperlipidemia, good relief was obtained at low risk in the young patients. The high mortality in the older age group was related to advanced and severely symptomatic coronary disease and ger:teralized atherosclerosis with myocardial infarction, stroke and renal failure the main causes of mortality. Despite this, symptomatic relief and graft patency were comparable in the survivors to that of the young patients.

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Absorption of tgtf-Albumin from the Pericardium by the Cardiac Lymphatics of Dogs. Sanford E. Leeds; Herman N. Uhley; Richard B. Meister; Kenneth McCormack, San Francisco Efferent cardiac lymphatic channels drain the heart and pericardium. Studies based primarily on the lymphatic drainage of the peritoneal cavity have been interpreted as showing that the principal lymphatic drainage of pericardium and other serous cavities is to the right lymphatic duct. There

CHEST, 70: 3, SEPTEMBER, 1976

have been few investigations of the lymphatic drainage of the pericardium. In order to determine the lymphatic pathways of absorption from the pericardium, 131I-albumin was instilled into the pericardial sac after cannulation of the right duct (RD) and the thoracic duct (TD) in anesthetized dogs. Radioactivity / ml (cpfim r ml) (it' concentration) was measured in lymph from the RD and TD and in blood serum, collected at intervals. Total radioactivity (cp5m/ml X lymph flow ml j hr) (ie content) was calculated for RD and TD lymph. Our results indicate that 131I-albumin is rapidly absorbed. The concentration of 131I-albuminjml is higher in lymph from the RD in all the experirnents. The average total radioactivity after two hours in ten experiments was higher in lymph from the RD than from the TD. However, both the RD and TD received 131I-albunlin from the cardiac efferent lymphatics which drain the pericardium and heart, and in four of ten experiments the TD received more 131I-albumin from the RD. This indicates that a multiple efferent lymphatic system exists for drainage of the pericardial sac and heart. The clinical implications are discussed. Stimulation of Ventilation by Dinitrophenol (DNP): Role of Tissue Hypermetabolism. Sanford Levine, Philadelphia 2,4-Dinitrophenol. a potent uncoupler of mitochondrial oxidative phosphorylation. elicits large increases in ventilation (VE) . These increases in ~E occur in the absence of conventional chemical stimuli in arterial blood. Nonetheless, we have suggested that the increases in VI-: elicited by DNP may be related to DNP-induced tissue hypermetabolism 0 Appl Physiol 38: 827-833. 1975). The present study examines this hypothesis by evaluating ventilatory and metabolic responses elicited by isomers of Dinitrophenol. Accordingly, 2.4-DNP (3 mg/kg) was infused into anesthetized dogs. Following 2.4-DNP infusion, VE increased 105 ± 17 percent and oxygen consumption (Vo 2) increased 107 ± 14 percent; arterial PC02 (PaC0 2) decreased [4 ± I mm Hg], arterial pH increased [.04 ± .01 units] and arterial oxygen saturation (5a02) remained constant. A second group of dogs was infused with 2.5-D~P (3 mg/kg) ; VE, Vo., PaC0 2 , art pH and 5a02 remained constant. A third group- of dogs was infused with 2.6-DNP (3 mg/kg) ; VE increased 42 ± 6 percent and V0 2 increased 30 ± 5 percent; PaC0 2, art pH and 5a02 remained constan 1. It is concluded that isorners of dinitrophenol exhibit similar structure-activity relationships with respect to (a) stimulation of ventilation and (b) stimulation of oxygen consumption. These results are consistent with the hypothesis that ventilatory stimulation by DNP may be related to tissue hypermetabolism. Detection of Cystic Fibrosis Heterozygotes by an Abnormal Response of Lymphocytes to Phytohemagglutinin (PHA). Jack Lieberman, Wallace Kaneshiro, Duarte, Cal. The detection of heterozygosity for cystic fibrosis (CF) is important for purposes of genetic counseling. Previous reports of abnormalities in cultured lymphocytes suggest that they may be utilized for this purpose. Forty-eight hour cultures of lymphocytes obtained by ficoll-hypaque gradient from both CF heterozvgotes and homozygotes were found to respond abnormally to PHA in autologous serum as determined by total-protein and ~-glucuronidase assay; 22 of 26 healthy adult controls showed increases averaging 45 percent in both total-protein and P-Klucuronidase, whereas 12 adult patients

CHEST, 70: 3, SEPTEMBER, 1976

with CF showed a mean decrease of 20 percent, and 25 heterozygotes showed no significant response to PHA. Failure of either total-protein or p-glucuronidase to increase by more than 10 percent (measured per 1010 cells) was consistent with the presence of a CF gene (either homozygous or heterozygous) . The baseline level of total-protein or tJ-glucuronidase in lymphocytes was not significantly different between those with a CF gene and controls, but when cultured in the presence of PHA the tJ-glucuronidase was lower in lymphocytes from CF patients (O.lll ± 0.068 vs 0.194 ± 0.121 units/ 1010 cells; P = 0.026). Further studies of lymphocytes in culture should be useful for studying the basic defect causing cystic fibrosis. Combination Chemotherapy for Squamous Cell Carcinoma of the Lung. William C. I.owe; William Mietlouiski; Roswell Phillips From April, 1974 to April, 1976, 139 patients with extensive well-differentiated and 83 patients with extensive poorly differentiated squamous cell carcinorna of the lung received chemotherapy in 18 Veterans Administration Hospitals. Chemotherapy was administered at random to four groups -eytoxan plus CCNU, cytoxan plus adriamycin, adriamycin plus CCNU and cytoxan alone. Using survival data as end points for evaluation, it was shown that the median survival for the well-differentiated variety was 12.0, 22.1, 15.2, and 12.1 weeks, and for the poorly differentiated variety, 23.6, 24.5, 30.0, and 8.7 weeks respectively. Using change in performance status according to the Karnofsky scale as the criterion for evaluation, it was shown that for these four groups of chemotherapy, improvement was seen in 17 percent (25), 16 percent (25), 7 percent (39), and 0 percent (35) in the welldifferentiated variety and in 21 percent (21),16 percent (17), 23 percent (15), and 10 percent (14) in the poorly differentiated variety respectively. For the agents used in this statistical study, it is concluded that combination chemotherapy achieves better results than single drug chemotherapy (cvtoxan) for squamous cell carcinoma of the lung. Successful Management of Refractory Tachyarrhythmias by Rapid Cardiac Pacing following Open Heart Surgery. Arthur ]. Lurie; Antone F. Salel; Zakauddin Vera; Dean T. Mason: Edward]. Hurley, Davis, Cal. Arrhythmias in postoperative cardiac patients occasionally pose a major therapeutic problem. From July. 1972 through June, 1975, 640 patients underwent open heart surgery. In this 36-month period, coronary artery bypasses were performed on 291 (45.3 percent) , valve surgery on 273 (42.6 pt.")'cent). and other procedures on 76 (12.1 percent). A wide spectrum and severity of arrhythmias were encountered in 55 percent of patients. In patients dying of pump failure, ventricular tachycardia and ventricular fibrillation were noted as terminal events. In eight patients, refractory ventricular tachycardia precipitated marked hemodynamic impairment and resulted in death in spite of large doses of antiarrhythmic drugs and repeated countershocks. However, in two similar patients, deteriorating rapidly with refractory tachyarrhythmias unchecked by vigorous conventional therapy, rhythm control was easily achieved by the introduction, as a last resort, of rapid rate (150-210jmin) pacing of the heart. One patient had acute massive anterior myocardial infarction and recurrent ventricular tachycardias, Infartectomy, to improve cardiac performance and to eliminate the focus of ventricular irritability was performed. Postoperatively. rc-

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fractory ventricular tachycardia continued. Overdrive suppression by ventricular pacing was effective in aborting ventricular tachycardia and suppressing further recurrences. The second patient developed refractory supraventricular tachycardias following aortic valve replacement. Ventricular overdrive suppression was the only effective method for the abolition and continued suppression of these arrhythmias. Rapid cardiac pacing is a safe means of controlling refractory tachyarrhythmias, eliminates the need of large doses of myocardial depressant drugs and can be undertaken in the early postoperative course before significant hemodynamic compromise is established. Routine insertion of a temporary epicardial electrode in postoperative cardiac patients is recommended.

The Mechanisms of Impairment of Alveolar Macrophage Defenses by Acute Exposure to Tobacco Smoke. Vijay Mahajan; Carlton McCarthy; John Shea; Denise O'Connell; Gary L. Huber, Boston Epidemiologic associations in man have linked tobacco cigarette smoking to an enhanced susceptibility to pulmonary infection. A model of intrapulmonary bactericidal inactivation was used to pursue this observation under controlled conditions in CD male rats. Inactivation rates of S aureus at six hours were calculated for an acute exposure after bacterial inoculation to an accumulative dose of 15, 30, 40, 50 and 90 cigarettes. Control animals inactivated 86.6 ± 1.2 percent of the staphylococci. A tobacco exposure of 30 cigarettes or less did not impair intrapulmonary antibacterial defenses, whereas increases in exposure to higher levels of tobacco smoke resulted in a progressive dose-dependent impairment, with a maximum effect after 90 cigarettes (71.5 ± 5.2 percent inactivation). Alveolar macrophages (AM) harvested from a low (30 cigarettes) and a high (90 cigarettes) tobacco smoke exposure were equivalent to controls in cell number and viability, and had no demonstrable alteration in in vitro bactericidal activity. Studies evaluating the temporal relationships between staphylococcal challenge and exposure to tobacco smoke suggested that any impairment in bactericidal function occurred during the process of bacterial phagocytosis. This impairment not only did not occur once the staphylococci were internalized by phagocytes within the lung, but smoke exposure resulted in an enhanced bactericidal capacity if delivered after phagocytosis was complete. When tobacco smoke exposure preceded rather than followed bacterial challenge, bactericidal activity was severely impaired (38.5 percent inactivation), although recoverable AM again had normal in vitro bactericidal function. These results imply that the antistaphylococeal defense system of the intact lung is acutely impaired in vivo only above a threshold level of tobacco smoke exposure. Furthermore, the toxicity of cigarette smoke can exert its effect only during the process of phagocytosis and may even enhance intracellular killing once phagocytosis is completed. Finally, the in vitro function of the AM per se is not acutely altered by tobacco under any in vivo exposure conditions, implying that the impairment observed is mediated not via AM but by an alteration in the acellular component of the bacterial defense system of the lung.

A Comparative Evaluation of Synthetic Smoking Materials and Natural Tobacco Smoke on the Antibacterial Defenses of the Lung. Vijay Mahajan; G. Clinton Sornberger; Alan Homans; Carlton McCarthy; Gary L. Huber, Boston Because of epidemiologic associations of tobacco cigarette consumption with lung disease in man, recent interest has

434 42NO ANNUAL SCIENTIFIC ASSEMBLY

centered on the development of total "tar" reduction by a potentially "safe" synthetic tobacco substitute. To compare the biologic effects of two currently available, nicotine-free synthetic smoking materials. Cytrel and New Smoking Material (NSM) , with natural tobacco smoke (IRI Kentucky reference cigarette) , rates of intrapulmonary bacterial inactivation were quantified in smoke-exposed and control animals. Following an intrapulmonary challenge of aerosolized S aureus, male CD rats were exposed acutely to fresh whole smoke from each product at six one-hour intervals. Using decachlorobiphenyl (DCBP) as a tracer, the amount of smoke particulate or "tar" deposited in the lungs of individual animals was monitored and correlated with the pulmonary bactericidal impairment, measured as the difference in percent bacterial inactivation at six hours post-inoculation in experimental animals and controls. While there was no nicotine in either product the total intrapulmonary particulate deposition after smoking Cytrel and NSM was only 16 percent and 13 percent, respectively, of the amount found after smoking natural tobacco, the degree of bactericidal impairment associated with synthetic smoking materials did not significantly differ from whole tobacco. These data imply that a gas-phase component of smoke, not "tar," may be cytotoxic to the lung and indicate that the alleged "safeness" of these synthetic materials, relative to tobacco. deserves further evaluation. The production of cigarettes with a reduced tar yield may lead to an increased personal consumption as compensation for the lowered tar delivery. Thus, the end result may actually potentiate rather than reduce any potential adverse health effects attributed to natural tobacco smoke inhalation in man.

Acquired Supravalvular Aortic Stenosis. John Mathieu; William G. Williams; Gordon Culham, Toronto Fourteen children have undergone reoperation for recurrent aortic stenosis at HSC between 1965 and 1975 inclusive. During the same period, 117 children have had a primary aortic valvotomy, two children required aortic valve placement as a primary operation for combined aortic stenosis with insufficiency, and one child required aortic valve replacement for insufficiency following a previous valvotomy. In 11 of the recurrences, the pathology was limited to the valve, and prosthetic replacement was necessary in four, while repeat valvotomies provided satisfactory palliation in seven. The other three children with recurrent aortic stenosis had narrowing of the supravalvular area. Pressure gradients prior to reoperation were 120, 170 and 100 mm Hg. The surgical pathology consisted of gross thickening of the sinus ridge and marked narrowing of the opening into one or more of the sinuses of Valsalva. Patch arterioplasty of the ascending aorta including the sinus, reduced the pressure gradients to 30, 50. and 5 mm Hg. Aortic valve replacement was not required in these three children. Recognition of this iatrogenic pathology is important in avoiding supravalvar stenosis after valvotomy and in avoiding unnecessary valve replacement in children with recurrent aortic stenosis.

Diagnostic Fiberoptic Bronchoscopy in the Immunoeompromised Host. Richard A. Matthay; Wayne C. Farmer; Dickson O. Odero, New Haven Fiberoptic bronchoscopy (FB) utilizing brush and transbronchial forceps biopsies is an established procedure for determining the etiology of focal and diffuse pulmonary in-

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filtrates. However, a study evaluating this diagnostic method in immunocompromised patients specifically has not been reported. Twenty-five procedures were performed on 19 irnmunocompromised patients (ages 19 to 75, average 44) with pulmonary infiltrates. Underlying diagnosis included lymphoma (8) ; leukemia (5); renal transplantation (2); histiocytic medullary reticulosis, primary lung cancer, multiple rnyeloma, and systemic lupus erythematosus one each. Eighteen patients had received chemotherapy and five radiotherapy. Thrombocytopenia was present in eight instances with platelet counts ranging frorn 2,400 to 90,000 (average 46,(00); PTT was prolonged in seven and PT was abnomal in three. Arterial hypoxemia was present in 16 cases (Pa02 40-67 mm Hg, average 54). Platelet transfusions were given for platelet counts <50,000 and supplemental oxygen was adrninistered to maintain Pa02 >50 mrn Hg. FB with hrush and forceps biopsies was diagnostic in II of 14 (79 percent) cases with diffuse lung disease and 10 of II (91 percent) with localized infiltrates. Mild bleeding occurred in two cases and a chest tube requiring pneumothorax in two. FB with transbronchial biopsy was safe and diagnostically accurate in this group of immunocompromised patients with pulmonary infiltrates.

Advances in the Salvage and Recycling of Thoracic Blood Loss. Kenneth L. Mattox; Lear Von Koch; Arthur C. Beall, Ir-. Houston Increases in traumatic thoracic injuries coupled with increases in cardiovascular surgery caseloads have resulted in requirements for rnore banked blood to replace losses. Techniques to recycle shed blood would lessen these demands and reduce the hazards of homologous blood transfusion. Five devices have been utilized to collect and recycle blood in more than 1,000 patients with intrathoracic bleeding. Two of these units utilized roller pump configurations, and in three, regulated negative pressure came from available hospital wall sources. Anticoagulation is achieved through the addition of local citrate solutions. These devices have been utilized in the emergency center, intraoperatively, and in the postoperative period. Each device has advantages as to site of utilization. Laboratory and clinical data support the safety of the concept of autotransfusion. Recovery of traumatic hemothorax and persistent postoperative thoracic blood losses provide the thoracic surgeon greater breadth of therapy.

Long Term Duration of Positive Myocardial Scans with Stannous Pyrophosphate in Patients with Ventricular Aneurysm. A luaro Mayorga-Cortes; Stuart Gottlieb; Stephen Mallon; David Sheps; Robert ]. Myerburg, Miami

99 m T ech netium

Eight patients with angiographically proven ventricular aneurysm (VA) and positive 99 m tech n etiu m stannous pyrophosphate (PYP) were followed by repeated PYP to evaluate the natural history of the positive uptake. All patients had a localized area of dyskinesis and severe two or three vessel coronary artery disease (CAD) C> 75 percent narrowing) Scintiphotos were obtained 90-120 minutes after intravenous injection of 15 mCi of 99 mT c PYP and were graded by three independent observers from (no uptake) to 4+ (intense uptake) . All eight patients had positive scans (2+4+) that were repeated serially over periods ranging from 2 to 18 months (average: 12 months) . During this follow-up period, no patient exhibited historical, electrocardiographic or enzymatic evidence of acute myocardial infarction (AMI).

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CHEST, 70: 3, SEPTEMBER, 1976.

All eight patients had posinve repeat scans which remained unchanged (± I grade), in terms of the intensity and location of abnormal myocardial uptake from the first to last studies. I t is concluded that the positive myocardial uptake seen in patients with VA may persist for long periods of time. On this basis, AMI should not be diagnosed because of a single positive scan in the presence of known or suspected VA. Persistently abnormal myocardial uptake would be in favor of the diagnosis of VA.

Pulmonary Resection in Metastatic Carcinoma. Patricia McCor"lack; Edward I. Beattie, jr.; Nael Martini, New York City Resection of pulmonary metastases in osteogenic sarcoma was reported by us to result in five-year survival rate of 27 percent. A later report of surgical management of pulmonary metastases from all types of sarcomas showed a five-year survival rate of 26 percent. This paper reviews the experience with 223 patients treated surgically for pulmonary metastases from carcinomas, demonstrating that survival of 25-30 percent is obtainable by surgical excision of these metastases. Surgical treatment is predicated on the absence of effective treatment by nonsurgical means. Two hundred twenty-three patients underwent 233 thoracotomies for metastatic pulmonary carcinomas. Most frequent sites of origin were genitourinary (26 percent), gastrointestinal (23 percent) , melanoma and breast (15 percent) . The majority underwent wedge resections or segmentectomy. When the following criteria was adhered to: control of primary site; absence of disease outside lung; preservation of lung tissue; and close followup with frequent chest x-ray examinations, surgical treatment of these metastases is justified.

Periodic Sustained Inflation (PSI): A New Modality for Treatment of Airway-Alveolar (A-a) Collapse. ]. Eugene Millen; john Lewis; Frederick L. Glauser, Long Beach Clinically, it is well appreciated that in the mechanicallyventilated patient with A-a collapse, sigh volumes do not effectively provide the volume history and time constants necessary to reach critical opening pressures. We therefore have developed a new modality: PSI, which allows the ventilator to deliver multiple inspiratory volumes until an airway pressure of 50-60 em H 20 is reached; this is sustained for 10-30 seconds. We studied three groups of dogs: cardiogenic pulmonary edema (7) -sigh and PSI increased baseline Pa02 (93 ± 48 mm Hg) by 4 ± 22 percent and 367 ± 136 percent respectively (P
The Role of the Leukocyte (WBC) in an Animal Model of the Respiratory Distress Syndrome. l- Eugene Millen; Deborah Smeltzer; Frederick L. Glauser, Long Beach Although the final common pathway of RDS is an increase in permeability of the alveolar capillary membrane (ACM), the syndrome remains multietiologic. Many investigators believe the WBC become trapped in the lung capil-

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laries, release lysozyme and disrupt the ACM. In five dogs, RDS induced by IV ethchlorvynol (15-20 mg/kg) an A-V decrease in WBC across the lung from 8.2 ± 2.4 X ..~ to 4.4 ± 1.6 to 1().3 mm 3 was found. To determine whether this leukopenia was a primary cause of the RDS we established an isolated, perfused, ventilated lung model and after obtaining baseline stable weights for 30 minutes injected ethchlorvynol into the input lines. Three groups (three experiments each) were studied and weight gain, as an indication of increasing lung water, observed: I-whole blood perfusion, weight gain of 2.5 ± I gm/5 min; II-plasma, weight gain 2.8 ± 1.1 gm/5 min; III-serum, weight gain 4.5 ± °1.6 grn/5 min. We conclude that ethchlorvynol induces RDS directly and the leukopenia is a secondary phenomenon related to intrapulmonary WBC trapping. Postexercise Systolic Time Intervals in the Midsystolic Click Syndrome. Alan B. Miller, Robert C. Bahler, Cleveland Postexercise systolic time intervals (STls) were measured in ten patients (study group) with phonocardiographic documentation. of the midsystolic click syndrome (MSC) and compared to eight age-matched volunteers (control group) with no evidence of heart disease. Following measurement of supine STls, the subjects pedalled an upright bicycle ergometer at progressive workloads un til a target heart rate (HR) representing 85 percent of the age adjusted maximum was attained, or an abnormal end point was noted. Immediately postexercise, a repeat measurement of STls was obtained. A shortened or unchanged postexercise left ventricular ejection time corrected for HR (.6.LVETc) and a marked shortening of total electromechanical systole after exercise (.6. QS2c) constituted a normal STI response to stress testing and was noted in all control subjects. All of the study group exhibited evidence of left ventricular dysfunction characterized by a prolonged .6.LVETc. It is concluded that left ventricular dysfunction can be demonstrated in patients with the MSC syndrome by the response of the postexercise STI. A Four-Year Study of 123 Programmable Pacemakers. Dryden Morse; Javier Fernandez; Gerald M. Lemole, Browns Mills, N.J. Starting in August, 1972 a new type of demand pacer was implanted which featured electromagnetic noninvasive control of the pacer rate and power output. Whereas we reported in 1973 an average pacemaker life of slightly less than two years (23 months) with standard demand units, a cumulative survival curve on the present (programmable) series calculated as outlined in the AAMI draft pacer longevity standard shows that 75 percent of the pacers are working at the 42month mark (3~ years) , and if those pacers that failed due to an early moisture problem in the sealed circuits are excluded, the 42-month pacer survival rat~ is 90 percent. A large part of the increased longevity was due to the fact that in 85 percent of those patients it was possible to turn the power ou tpu t down to 4.0 rna (less than half the usual pacer output of 9 rna), although integrated sealed circuits also were a factor. This decreased use of power possible in a programmable pacer is particularly significant as we begin to employ lithium programmable units (we can report only a six-month preliminary experience with these) since lithium batteries characteristically have little deterioration with time alone (unlike mercury cells) and therefore can be expected to take full advantage of any low output mode or standby mode of operation. Standby pacer position can be more fre-

436 42ND ANNUAL SCIENTIFIC ASSEMBLY

quently attained with the ability to set the pacer rate down to 60 pulses per minute. Twenty percent of our patients were reprogrammable in rate with clinical benefit; this also allows sinus rhythm at 60 to 70 to take over and is another example of the advantage of programmability. Thus, there is a peculiar multiplicative felicity to the programmable lithium unit in terms of increased longevity. Cardiopulmonary Effects of Continuous Positive Airway Pressure. Gary S. Mintz; Mark Davis; Ellen Eidelson; Martin F. Hayes, Jr., Philadelphia A mainstay in treating neonatal respiratory distress syndrome, continuous positive airway pressure (CPAP), is now being used to treat adult respiratory insufficiency. A similar modality, mechanical ventilation with positive end-expiratory pressure (PEEP), may decrease cardiac output (CO) and cause hypotension. The cardiovascular effects of CPAP are not well established. CO, A-V O 2 difference, and pulmonary capillary wedge pressure (PCWP) were measured in six patients at different levels of CPAP (0, 3, 6, 9, and 12 em H 2 0 ) . CO, A-V O 2 difference, and blood pressure did not change; PCWP neither changed nor increased. Two patients had chronic obstructive pulmonary disease (COPD); four patients did not. CPAP augmented arterial 1'02 in patients without COPD, but did not in patients with COPD. Arterial Pco2 and pH did not change in any patient. Unlike PEEP, CPAI' does not decrease CO or blood pressure perhaps because inspiratory augmentation of venous return is preserved. CPAI' may be more effective in increasing oxygenation in patients without COPD than in patients with eOI'D. Risks and Benefits of Postoperative Cardiac Catheterization in Patients with Caged Ball Valve Prostheses. Mark Morton; John McAnulty; Shahbudin Rahimtoola, Portland, Oregon One hundred six consecutive postoperative cardiac catheterizations, (POCC) in 100 patients with caged ball-valve prostheses (BVP) were evaluated. Indications for POCC included: clinical-hemodynamic deterioration (CHD) 59 percent, routine hemodynamic evaluation 20 percent, arterial emboli 27 percent, hemolysis 12 percent, and other 6 percent. Ninety-one transeptal left heart and 77 retrograde femoral artery catheterizations, and 17 transthoracic left ventricular punctures with ventriculography (TTLVP) were performed. Major complication rate (MC) 8.5 percent included: four excessive bleeding, two cerebral emboli, one ventricular fibrillation, two other. No deaths, myocardial infarcts or infective endocarditis occurred. Me for POCC with TTLVP, 24 percent (4/17) and therapeutic anticoagulation, 18 percent (6/34) were higher than MC without these risk factors, 2 percent (1/60). Significant abnormality (S) was detected in 55 percent and reoperation (R) performed following 34 percent of all POCC. In patients with CHD incidence of S, 75 percent (57/63) and R, 51 percent (32/63) was higher (I' .(01) than in patients without CHD [S 19 percent (8/43) and R 9 percent (4/43»). TTLVP with ventriculography, and therapeutic anticoagulation were associated with increased risk for MC at POCC. Patients with BVP who manifest clinical hemodynamic deterioration should undergo POCC because of the high incidence of correctable abnormalities.

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Red Cell Oxygen Transport in Obstructive Pulmonary Disease. Everett Murphy; Roger Bone; Charles Hiller; Dennis Diederich; William Ruth, Kansas City, Kansas Little is known about red cell oxygen transport in patients

CHEST, 70: 3, SEPTEMBER, 1976

with various types of respiratory insufficiency. The purpose of this study was to study three parameters which affect red cell oxygen transport-2,:J DPG, adenosine triphosphate (ATP) , and PrlO-in the following groups of patients: group 1-25 stable COPD patients; group 2-1:J stable steroid-dependent asthmatics receiving daily equivalent steroid dosage of 12 mg ± 4.4; group :J-Il stable steroid-independent asthmatics; and group 4-5 COPD patients in acute respiratory failure (ARF) on day 0, day 2 (group 5) and day 6 (group 6) of their clinical course. These data will be presented. Stable COPD and asthmatic patients had the same 2,~ DPG and ATP values despite different FEV t values. Chronic corticosteroid administration had no effect on red cell oxygen transport. The acutely ill COPD patient, after correction of acidosis and hypoxemia, regained normal 2,:JDPG values within 48 hours (P <0.05) and remained stable. Economic, Bronchial and Parenchymal Resection (or Bronchogenic Carcinoma. A. P. Nae], ]. Schmid De Gruneck, Yuerdon, Switzerland Application of "minimal" resection for bronchogenic carcinoma is justified by limited pulmonary reserve, possible enhancement of immunocompetence by "tumor reduction" and favorable long-term results. Thirty-two sleeve-lobectomies and 42 segmentectomies were performed. The indications should be selective and will be discussed. Twenty-three segmentectomies were done on the left and 19 on the right side. The risk of local recurrence should not be increased (2 of 74 cases) . The majority of patients were operated for epidermoid or adenocarcinoma (61 cases). Oat-cell and large cell or bronchioalveolar carcinomas were resected only for an uncertain diagnosis or a very poor pulmonary function. Ideal indications for a small tumor without lymph gland involvement (40 cases) should be distinguished from compromiseindications (:J4 cases) motivated by poor respiratory reserve. Results depend upon indication and operation. Postoperative mortality was 4.6 percent. Five-year survival after a curative segmentectomy or sleeve-resection is 49 percent or 26 percent, whereas it is only 6.2 percent and nil after "incomplete palliative," segmental or bronchial resection. These results justify "economic resection" for bronchogenic carcinoma in well selected cases. In addition to a reasonable quota of cancer cures, the quality of survival is improved and maybe immunocompetence is enhanced by "tumor reduction" with a better chance of success for adjuvant chemo- or immunotherapy. Electrocardiographic Abnormalities in lapse Syndrome (MVPS) Mimicking ease (CAD). Charles Z. Naggar, with Pamela Harrigan and Lori Downing,

the Mitral Valve ProCoronary Artery Distechnical assistance of Boston

MVPS is Dot, as commonly believed, a disease of the young adult. Our experience revealed that echocardiographicallyproved MVPS was first diagnosed in 124 patients between the ages of :JI and 70 years; many had symptoms suggesting CAD. The resting ECG (RE) and su bmaximal exercise testing were analyzed for ST-T abnormalities (STY A) and ventricular extrasystoles (VE). Of the patients, :J4 percent had STTA during RE. Exercise precipitated ST depression 1.0 mm in 1:J patients; none had angina pectoris or myocardial infarction. Incidence of VE from the fourth to the seventh decades were: 22 percent, :JO percent, :J4 percent, and 25 percent respectively. Our results compared to those obtained in normal and CAD patients will be presented.

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We conclude that: MVPS is prevalent in the coronaryprone age population, incidence of VE in MVPS is higher than normal population, and echocardiography should be performed whenever dou bt overshadows the diagnosis of CAD. Clinical Profile of the Mitral Valve Prolapse (MVP) Syndrome in Ambulatory Patients. Charles Z. Naggar; Sidney A lexander; Donald Breslin; with technical assistance of Pamela Harrigan, Lori Downing, Boston In a referral practice of a largely ambulatory population, 161 patients with echocardiographically-documented MVP were seen in an 18-month period. Mean age was 44 years, with female preponderance 2.3: I. Presenting symptoms were atypical chest pain (ACP), 40 percent; palpitations, 55 percent; fatigue, :JO percent; syncope, 3 percent, and dyspnea on exertion, 19 percent. Three patients had bacterial endocarditis (BE) , 128 patients had either midsystolic click (MSC) and/or late systolic murmur, and :J:J patients had neither MSC or LSM. Electrocardiographic analysis revealed a 7 percent incidence of left atrial conduction delay, M percent with ST-T abnormalities (STTA) -2/:J localized to the inferolateral leads -and 6 percent with LVH. Ventricular extrasystoles were documented in 29 percent of the entire group. Six patients had associated interatrial septal defects, and the remainder were free of any cardiovascular disease. MVP syndrome is a largely benign, common cardiac affliction in the adult. Electrocardiography may be indicated in patients with ACP and STTA even in the absence of auscultatory findings of MVP. Pulmonary Embolism in Respiratory Failure. Aron Neuhaus; Rodney R. Bentz; John G. Weg, Ann Arbor The incidence of pulmonary embolism (PE) and the value of lung scans were studied in a group of patients with respiratory failure. Of 617 admissions with respiratory failure, 88 had lung scans. There were 102 deaths and 66 autopsies. Three subpopulations were studied: I) 12 patients with lung scans and pulmonary arteriograms, 2) II patients with lung scans within few days prior to autopsy, and :J) 66 autopsy examinations. There was no correlation between lung scan and arteriogram results in 9 of 12 patients. The lung scan did not correlate with autopsy findings in 9 of II patients. PE was found in 18 of 66 autopsies (27 percent) with half of them not suspected clinically. In none was PE the primary cause of death, but in 8 of 18 patients, PE was a contributory cause of death. Physical examination, chest roentgenogram and electrocardiogram results were nonspecific and could not predict PEe These data indicate a high incidence of PE in patients dying with respiratory failure, and also that lung scans are not a reliable diagnostic tool to demonstrate or exclude PE in patients with respiratory failure. Sudden Death Syndrome Associated with Heritable Q-T Interval Prolongation. Richard M. Newton, William S. Elias, Charlottesville, Virginia We present the 82nd symptomatic case of heritable Q-T prolongation syndrome, with recurrent paroxysmal ventricular fibrillation. Severe episodes, both self-limited and requiring defibrillation, began postpartum. Intravenous lidocaine controlled the ventricular fibrillation. QT-C increased to 0.682 sec with giant T waves occupying over 50 percent of this interval. Onset of ventricular tachycardia precipitated by a premature atrial beat falling in the increased vulnerable

42NO ANNUAL SCIENTIFIC ASSEMBLY 431

phase is shown, as well as strips of extremely bizarre configurations and rapidly changing atrial and ventricular arrhythmias. Emotional stress precipitated several episodes. The asymptomatic syndrome was present in the patient's mother, sister and grandmother. This is only the fifth time that Q-T prolongation in more than two generations has been reported. Our patient was ultimately controlled with diphenylhydantoin and propranolol. She has had no more episodes in 16 months of followup.

The Effect of Tracheal Tube Cuff Pressure on Microcirculation and Ultrastructure of the Rabbit Tracheal Mucosa. ViI Nordin, C. E. Lindholm, Uppsala, Sweden Capillary blood perfusion of the rabbit tracheal mucosa has been studied by injection of isotope-labelled microspheres. Normally, the perfusion of the mucosa is about 0.3 mlyrninute per gram mucosa, (about 60 percent of the cerebral blood flow per gram tissue). When a tracheal tube is inserted, the blood perfusion of the tracheal mucosa usually shows a more than tenfold increase. It may be predicted that the commonly used small-resting-diameter, small-resting-volume cuff stops the microcirculation in the mucosa covering the tracheal cartilages at cuff-to-tracheal wall pressure (C-T pressures) as low as 30 mm Hg. The large-resting-diameter, large-restingvolume cuff, il really ideal, would not seriously hinder the capillary blood perfusion of the tracheal mucosa until the C-T pressure approaches the systemic arterial mean pressure, ie about 85 mm Hg. No cuff, however, has this property and we can not, therefore, give general figures for a safe C-T pressure range, as this will vary with the quality of the cuff. The large cuff should have as thin and flexible walls as possible, so that it will drape evenly over the mucosa. The best guarantee for maintaining a satisfactory blood flow along the entire mucosa and for preven ting a risk of local ischemia is for the cuff wall to be so thin as to be almost non-existent, as near as possible giving the cuff the quality of an air cushion. The tracheal mucosa is very easily damaged by even a very slight C-T pressure. On the other hand, the damage usually is very superficial and the basement membrane of the mucosa is fairly resistant. The healing capacity of the mucosa is very good; complete regeneration of damaged mucosa takes place usually within 15 days, and after that time, the mucosa does not have any visible ultrastructural damage left.

Combinations of Four Physical Signs as Indicators of Ventilatory Abnormality in Obstructive Pulmonary Disease. Neely E. Pardee; Edward A. Morgan; C. James Martin, Seattle During an evaluation of the usefulness of physical signs in diagnosis of obstructive pulmonary syndromes, 183 patients underwent both ventilatory tests and standardized physical examinations. Physical signs gave a good indication of ventilatory function, though they failed to identify some subjects with modest defects. Examiners made a semi-quantitative estimate of intensity of breath sounds in brisk deep inspiration. They recorded palpable recruitment of scalene muscles at rest, expiratory wheeze with rapid deep breaths, and moist crackle with cough as present or absent. Grading the findings by assigning one point for borderline breath sounds, two for definitely reduced breath sounds, and one for presence of each of the other signs produced an index with a range of 0 to 5. Index values had a strong negative correlation (P less than 0.01) with forced expired volume at one second (FEV1). Differences in grading performance between four examiners were not statistically significant.

438 42ND ANNUAL SCIENTIFIC ASSEMBlY

A Longtenn Prospective, Retrospective and Autopsy Study of Laryngeal Effects of Prolonged Endotracheal Intubation (or Acute Respiratory Failure. Mah en dra Patel; Benjamin Zielinski; Nathan S. Serii]; Aoraham Ham-pel, Queens, New York

The use of prolonged laryngotracheal intubation for continuous mechanical ventilation in adults with acute respiratory failure continues to be a controversial subject. Our experience in a respiratory intensive care unit over an eightyear period has led us to the belief that prolonged oral endotracheal intubation is both safe and efficient. In addition, it eliminates the small but real mortality of tracheostomy, Also, it has been shown that complications at the cuff site, (tracheal stenosis and tracheoesophageal fistula), occur no more commonly with cuffed endotracheal than with cuffed tracheostomy tubes. Little is known, however, about the laryngeal effects resulting from prolonged oral endotracheal intubation. This study included a total of 65 patients intubated for a mean period of 12 days. Twenty patients died. Of the remaining 45, 38 were followed-up prospectively, and 7 retrospectively, so that information was available as to the state of the larynx up to one year postextubation. Seventy percent of the patients had moderate to severe hoarseness immediately after extubation. Laryngoscopy indicated that this was due to immobility of one or both cords. However, follow-up showed marked to complete recovery of laryngeal function and cessation of hoarseness in 86 percent of the patients, the remainder experiencing only mild hoarseness. Three patients developed upper airway obstruction, post extubation, and had to be tracheostomized , In two, it was due to bilateral immobility of the vocal cords in adduction, and in the third patient, subglottic granulation tissue was noted. Of the first two, improvement in cord mobility and voice is still occurring at I Y2 months post extubation in one, and we hope decannulation will soon be possible. 'The second is lost to follow up. In the third, the subglottic lesion is only five weeks old, and hopefully will improve. Autopsy evidence of significant acute laryngeal damage was seen in three' patients and will be demonstrated. Factors possibly leading to the laryngeal damage will be reviewed. We feel that oral endotracheal intubation is the airway of choice in adults with acute respiratory failure requiring mechanical ventilation and can be maintained for a prolonged period of time, without a high incidence of cornplications, and with no mortality.

Clinical and Immunologic Consequences of Thymomas. Carlos A. Pellegrini; Torn R. DeMeester; Mark Lawrence; David B. Skinner, Chicago Limited knowledge concerning the immune function of the thymus gland and failure of histology to accurately determine malignancy have made the natural history of thymic tumors most unpredictable. From 1950 to 1975, 36 patients with primary thymic tumors were seen at the University of Chicago; 22 were classified as invasive tumors based on the extension into adjacent structures on gross examination, 14 were classified as noninvasive. Nine patients had associated myasthenia gravis. Of the 22 patients with invasive tumors, 5 had lymph nodes or distant organ metastasis. Four patients developed a second carcinoma. Treatment consisted of surgery alone (6), surgery plus radiation (6), radiation alone (7) and nothing (3) depending on the stage of the disease. The best survival followed surgical therapy. Of the 22 patients, 8 died from their

CHEST, 70: 3, SEPTEMBER, 1976

thymic tumor, with widespread metastasis in three; 3 died from associated myasthenia gravis, 2 died from a secondary neoplasm. Of the 14 patients with noninvasive tumors, six patients developed a second carcinoma and four died from it at 2 months, 12, 16 and 23 years. Twelve patients had surgical removal of the tumor and 2 were not treated, both of whom died of myasthenia gravis. Eight postoperative patients survived 5 or more years, and 3 are alive less than 5 years. It is concluded that: prognosis of thymic tumor is related to its invasive nature on gross examination and cure from invasive thymomas occur only with early extirpative surgery; invasive thymomas do give rise to distant organ metastasis; in patients with thymic tumors there is a high incidence (28 percent) of associated second cancer; patients with noninvasive thymomas have a good result from surgery but have a 45 percent chance of developing a second carcinoma.

Colloid Osmotic Pressure as a Prognostic Indicator in Critically III Patients. Eric Rackow; A Ian Fein; Jeffrey Leppo, Brooklyn Colloid osmotic pressure (COP) was determined in 15 normal subjects with a mean of 25.5 ± 1.4 mm Hg and 128 critically ill patients with a mean of 20.4 ± 4.4 mm Hg (P .001) . The critically ill patients were divided into three clinical groups: 71 with no pulmonary edema (NPE) , COP of 21.5 ± 4.0 mm Hg; 40 with cardiogcnic pulmonary edema (CPE) , COP of 21.4 ± 2.6 mm Hg; 17 with noncardiogenic pulmonary edema (NCPE), COP of 13.6 ± 3.4 mm Hg. The NCPE patients' COP was significantly lower than that of the NPE and ePE patients (P .001) . There was no significant difference between the COP of NPE and CPE patients. The COP of the 86 survivors was 22.0 ± 3.6 mm Hg versus 17.2 ± 4.4 mm Hg in the 42 deaths (P .001). Furthermore, COP was significantly lower in the dying patients within each of the three groups (P .001). Low COP is a reliable prognostic index for the development of noncardiogenic pulmonary edema and mortality in critically ill patients.

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Mitral Valve Prolapse in Patients with Coronary Artery Disease. Echocardiographic-Angiographic Correlation. Veena Raizada; Flauio D. Reich; Alberto Benchimol; Kenneth B. Desser; Connie Sheasby; Phoenix Echocardiography (ECHO) was performed in 25 consecutive patients with angina pectoris and angiographcally-demonstrable coronary artery disease. No subject had a systolic click on auscultation. ECHO detected late or pansystolic mitral valve bowing suggestive of MV prolapse in 6/25 (25 percent. Left ventricular angiography demonstrated prolapse of the anterior mitral valve leaflet, posterior mitral valve leaflet or both leaflets in 15/25 (60 percent) . The degree of coronary artery disease in the study group was: single vessel, n==3; double vessel, n==1; triple vessel, n== II. Thirteen of 15 subjects with angiographic evidence of prolapse had left ventricular asynergy: anterior, n==3; anteroapical, n==2; inferior, n==7; inferoposterior, n== I. Five of 6 patients who had ECHO evidence of mitral valve ballooning manifested angiographic findings compatible with prolapse. A single subject with prolapse had mitral insufficiency. It is concluded that mitral valve prolapse is frequently observed in patients with triple vessel coronary artery disease and inferior wall asynergy; ECHO will detect such prolapse in only 1/3 of affected patients but is highly specific when positive; angiographic evidence of mitral insufficiency is unusual in patients

CHEST, 70: 3, SEPTEMBER, 1976

with coexisting coronary artery disease and mitral valve prolapse.

Closing Volumes with Changes in Wedge Pressure. David Rice; Warren Simi; Carlos Bedrossian; Warren Miller, Hous-

ton Closing volumes (CV) were measured in anesthetized mongrel dogs while pulmonary capillary wedge pressure (PCW) was increased in increments. pew was varied by way of a left atrial balloon which had been inserted during thoracotomy. To measure ev by the single hreath nitrogen method, following thoracotomy closure the lungs were inflated with oxygen and then emptied using a withdrawal syringe. In a control group of five dogs there was no change in CVover the same time period as the study group. In the study group CV, as a percent vital capacity, were measured immediately (period I) and 20 minutes following (period 2) elevation of the PC\V in six dogs. These data will be presented. We could find no relationship between CV and PCW until the PCW was elevated to a level which would be expected to produce pulmonary edema.

Prolonged Intra-Aortic Balloon Pumping in Klebsiella-Induced Sepsis. Arthur J. Roberts; Eddie L. Hoover; John R. Combes; Daniel R. Alonso: wuus». A. Gay, Jr.; Valavanur A. Subramanian, New York City Recent experiments suggest that decreased coronary perfusion pressure causes myocardial depression in sepsis. In this study, intra-aortic balloon pumping (IABP) is used to increase coronary perfusion in an attempt to improve the course of hypodynamic septic shock over a 24-hour period. Twelve anesthetized closed chest mongrel dogs were given an intravenous injection of 2 X 1010/kg live Klebsiella or'ganisms in divided doses. At one hour after induction of shock, the dogs were divided equally into control or IABP groups. Right atrial pressure was maintained at preshock levels with Ringer's lactate to prevent intravascular volume depletion. Hemodynamic measurements and blood gas determinations were monitored frequently. Myocardial depression was not seen in either group for the first five hours but at 24 hours, left ventricular stroke work in IABP was 39.2 ± 2.9 gram-meters while only 20.1 ± 2.7 in controls (P .01) . Myocardial performance curves at 24 hours were also better in IABP. Systemic vascular resistance was increased to 6,420 ± 425 dynes-sec-em -5 in controls, while only 2,994 ± 294 in IABP (P .01) . Respiratory insufficiency was not seen in either group documented by near normal arterial P02 levels and pulmonary histology. Light microscopic evidence for necrosis in kidney, liver and small bowel were seen in both groups, but larger areas of necrosis were seen in controls. Electron microscopic studies of left ventricular myocardium in IABP showed only nonspecific edema with mitochondrial preservation while myocardial high energy phosphate levels were maintained at near normal levels

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in both groups.

Leaper's Lung-Respiratory Sequelae of Massive Blunt Chest Trauma. Thomas Robertson: Leonard D. Hudson; S. Lakshminarayan, Seattle Sixteen survivors of 139 persons falling 165 feet to the water from Seattle's Aurora Bridge were reviewed. Five men and II women (mean age 29) survived, while 83 men and 43 women (mean age 42) succumbed. Fifteen are long term survivors. Clinical features included ecchymoses (14 patients) ,

42ND ANNUAL SCIENTIFIC ASSEMBLY 439

bilateral rales (10), shock (9), and bloody sputum (6). Blood gas levels obtained in II patients showed significant hypoxemia. Five had Pa02 50 on a Flo2 of 1.0. Eight required assisted ventilation (mean 7.9 days) and 3 required ~ 20 an H 20 of PEEP. The initial chest roentgenograms showed patchy parenchymal infiltrates in 12 patients. Pneumothorax developed in 10 patients and was bilateral in 3. Rib fractures were noted only in the 3 oldest subjects. Frequently associated injuries included spleen and liver lacerations. These manifestations of blunt thoracic trauma resemble pulmonary blast injury. Salvage is dependent upon prompt rescue and respiratory support.

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Rationale for Re-Testing with PPD following Chemoprophylaxis; A Child-oriented Program. Irving 1. Rubin, Clement Curd, Pittsfield, Mass. This is a ten-year study of 483 patients who have been repeatedly re- tested following one or more years of chemoprophylaxis with 10 mg INH per kilo to find a scientific as well as an empirical guideline. It is based on a Berkshire County, Mass., school population of 34,000 per year from 1966 through 1975 for a total of 340,000. They were divided in three groups: group I, 247 documented recent converters .(207 [84 percent] reverted to negative); group 2, 62 unknown date of conversion, to PPD (43 [69 percent] reverted) ; group 3, 71 known positive for years (36 [51 percent] reverted) . The remaining 103 either were not re-tested or were receiving chemoprophylaxis. This year we have re-evaluated 338 subjects: 220 (65 percent) remained consistently negative, 118 (45 percent) have remained or again have become positive. These findings may suggest that: elimination of the bacillus reverts the skin test; some are infected with resistant organisms and should receive some other drug; some who convert again should remain under long-term surveillance.

Flexible Fiberoptic Bronchoscopy and Endobronchial Tamponade in the Management of Massive Hemoptysis. Eng C. Saw, Leon S. Gottlieb, Los Angeles From June, 1975 thru January, 1976, emergency bronchoscopy was performed for massive hemoptysis in nine consecutive patients using a flexible fiberoptic bronchoscope. Causes of hemoptysis included cavitary tuberculosis (6); bronchiectasis (2); pulmonary contusion due to blunt trauma (1 patient) . The tracheobronchial tree was systematically lavaged and bleeding was localized to the segmental and subsegmental levels in all cases. The bleeding site was selectively cannulated with a No. 4Fr Fogarty catheter inserted through the channel of the flexible fiberoptic bronchoscope and the balloon was inflated with 3/4 ml of a radiopaque dye to occlude and tamponade the bleeding focus. The proximal end of the catheter was clamped with a hemostat and the hub cut off. A straight-pin plug was inserted into the catheter to maintain pressure in the inflated balloon before the hemostat was removed. The bronchoscope was withdrawn over the Fogarty catheter, leaving the inflated balloon in place. The efficacy of balloon tamponade was assessed by re-inserting the bronchoscope, and observing the bleeding area. The position of the inflated balloon was verified by serial chest roentgenograms. This technique was effective in controlling lifethreatening hemoptysis in nine patients considered unsuitable for surgical resection due to prohibitive decrease in 'pulmonary reserve or other causes. There was no mortality or serious morbidity associated with this procedure.

440 42ND ANNUAL SCIENTIFIC ASSEMBLY

Experimental and Clinical Evaluation of a New Negatively Charged Bovine Heterograft for Use in Peripheral and Coronary Revascularization. Philip N. Sawyer; Boguslaw Stanczeuiski; Thomas R. Lucas; Martin l- Kaplitt; Frederic J. Vagnini, Manhasset, New York A suitable substitute to replace saphenous veins as aortocoronary bypass conduits has not yet been found. The benefits of such a new conduit would include reliability, availability, resistance to thrombosis, better handling properties and the elimination of tedious dissection with its attendant morbidity. Such a graft must have comparable or superior patency rate when compared to saphenous vein. In an attempt to provide a solution to this problem, a negatively charged bovine heterograft has been developed and utilized in both the laboratory animal and in patients in both the peripheral and coronary circulation. These prosthetic devices, in addition to their negative charge, have been proteinized with subsequent gluteraldyhyde tanning to produce a fine leather-like structure which in longterm implantation in the dog proved very resistan t to thrombosis for periods longer than one year when evaluated grossly, photographically, histologically and scanning electron micrographically. These prosthetic arteries of biological origin appeared superior to all of the several materials and artery types tested now or previously. They have now been implanted in the peripheral vascular tree of 25 men as axillary-femoral, femoral-popliteal, aorto-fernoral-popliteal and renal bypasses. Implanted for periods up to nine months, they have proven superior to any other type of graft material heretofore implanted in man with patency at the 90 percent level in all patients. Their most striking characteristic has been a resistance to thrombosis at low flow rates. In view of this experience, selective aortocoronary implantation of a 4 mm version of this graft has been carried out in seven patients with longterm multiple implantation in three. Initial experience in early follow up has been very gratifying. These grafts are now being utilized as an alternative to missing saphenous veins when indicated for coronary revascularization. Cell-Mediated Immunity in Silicosis. Mark Schuyler; John

Salvaggio; Morton Ziskind; Hans Weill, New Orleans Cell-mediated immunity was evaluated in 14 patients with silicosis (10 with conglomerate masses) and 10 age-matched controls. Forty-eight hour skin test responses to PPD, SKSD, Candida and Trichophyton were measured. Peripheral blood lymphocyte responses (3HTdr uptake) to phytohemagglutinin (PHA, 75.0 and 7.5p. g/ml) , pokeweed mitogen (PWM, 1:10 and 1:50), concanavalin A (Con A, 10.0, 1.0 and O.IJL g/ml) and the above antigens were determined. T cell (SRBC rosettes) and B cell (zymosan-complement [zq rosettes) lymphocyte percentages were calculated. There were no significant group differences (P 0.05) of the following: SRBC and ZC rosettes, number of positive delayed skin tests, lymphocyte responses to PHA and antigens. The silicotic group had significantly (P 0.05) lower lymphocyte responses to PWM and Con A. These data suggest that chronic respiratory tract exposure to silica, a potent macrophage toxin, selectively depresses some of the parameters of mononuclear cell function but does not otherwise effect systemic cell-mediated immunity.

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High Altitude Pulmonary Edema in a North American Community. Charles H. Scoggin; John T. Reeves; Robert F. Grover, Denver High altitude pulmonary edema (HAPE) is a unique con-

CHEST, 70: 3, SEPTEMBER, 1976

dition which has never been studied in a North American high altitude population. Therefore, we retrospectively analyzed all cases of HAPE hospitalized in Leadville, Colorado (altitude ~IOO meters) from November, 1970 to June, 1975. Twenty-nine individuals were treated for HAPE (13 females and 16 males) ranging in age from 3 to 41 years (average 13.5 years). All but two were native to high altitude, and 28 of 29 had reascended to high altitude prior to onset of symptoms. Cough (20{29), shortness of breath (17{29), and vomiting (8{29) were the most common symptoms. Slight fever (13/29), rapid pulse and respirations (29/29), and pulID()nary rales (29/29) were the most frequent physical findings. All had radiographic pulmonary edema. All survived, responded rapidly to oxygen therapy at high altitude, and were able to remain at high altitude. We conclude that there is a significant incidence of HAPE in a North American high altitude population; the young of either sex are most frequently affected; HAPE responds rapidly to oxygen therapy at high altitude.

False-Positive Cytologic Diagnosis of Lung Carcinoma in Patients with Pulmonary Infarction. William G. Scoggins; Rodney H. Smith; William J. Frable; Walter J. O'Donohue, [r.; James W. Brooks; Lazar J. Greenfield, Rich mond, Va. Cytologic examination of specimens obtained from the tracheobronchial tfee has become an integral part of the evaluation of pulmonary lesions. Cytologic criteria for the diagnosis of carcinoma exist and are well defined; however, certain benign processes may possess features strongly suggestive of carcinoma of the lung. We will present three cases in which a positive cytologic diagnosis of carcinoma of the lung was made by an experienced cytopathologist. At surgery, each patient was found to have pulmonary infarction and no evidence of carcinoma. Two of the false-positive diagnoses were made on material obtained by brush biopsies during flexible bronchoscopy. The third false-positive diagnosis was made from a bronchial washing obtained during Jackson bronchoscopy. Review of this experience has disclosed clinical and cytologic features which should alert the clinician to the possibility that the cytologic diagnosis of lung cancer may be misleading in certain specific disease processes.

Pulmonary Alveolar Protcinosis: The Physiologic Response to Exercise After Whole-Lung Lavage in Nine Patients. Paul A. Selecky; Karlman Wasserman; Michael G. Cleary, TO'f'ranee, Cal. We used whole lung lavage in the treatment of 14 patients with pulmonary alveolar proteinosis, and documented the clinical and physiologic responses in nine. The patients were evaluated before and after both lungs were separately lavaged. Incremental exercise tests were performed on each of the nine patients, with on-line monitoring of multiple ventilatory parameters, as well as arterial blood gas levels. Other physiologic studies included measurements of standard pulmonary function variables (including DLco), dynamic compliance, and resting arterial blood gases; chest x-ray films were also obtained. The treatment of this disorder has included a variety of whole-lung lavage techniques, but our experience with 14 patients has resulted in a protocol which includes: I) unilateral whole-lung lavages. two to four days apart under general anesthesia; 2) isotonic saline solution as the lavage solution; 3) use of a mechanical chest percussor during lavage; .and 4) using the dynamic com pliance of the lavaged lung in the immediate postlavage period as a guide

CHEST, 70: 3, SEPTEMBER, 1976

for extubation. This lavage technique has removed an abundant amount of proteinaceous material in each instance, and is followed by an improvement in dynamic compliance of the lavaged lung to near-normal levels within 60 minutes postprocedure. As a result, patients are symptomatically improved, and the chest x-ray picture returns to normal. Physiologic studies likewise reveal a dramatic improvement in all ventilatory parameters, with a return to normal in most patients.

A Graphic Approach to Assess Vpf'PaC02 -V n / V T Relationships in Patients on Respirators. Paul A. Selecky; Mark Klein; Karlman Was.~erman, Torrance, Cal. In order to facilitate the care of patients receiving continuous respirator support, we constructed a graph illustrating the physiologic interrelationships between minute ventilation (~E)' PaC0 2 and the dead space-tidal volume ratio (Vn/VT ) . With the measurement of simultaneous VE and PaC0 2 , the clinician can use the graph at the bedside to quickly determine Vn/V T of the patient, and then' to use the Vn/V T curve as a guidelinee in adjusting the respirator, ie, to determine the ~ E necessary to achieve a desired PaC02 • We have corroborated the validity of the graph and demonstrated its clinical application on a group of critically ill patients on continuous ventilators. Using the graph, it was possible to accurately predict the change in PaC0 2 resulting from a change in VE. The graph also permitted us to determine any changes in Vn/V T that occurred as a result of a change in the patient's respiratory status.

Cardiopulmonary Effects of Marihuana Smoking during Exercise. Bertrand ]. Shapiro; Sheldon Reiss; Stuart F. Sullivan; Donald P. Tashkin; Michael S. Simmons; Robert T. Smith, Los Angeles The effects of smoking marihuana combined with exercise upon arterial blood gas levels, arterial lactate, minute ventilation ~E)' 02 consumption (~o2)' CO 2 production (~c()..l)' respiratory exchange ratio (R), end tidal CO2 (FETco2)' respiratory rate (f) and electrocardiograms were compared to the effects of exercise alone upon those parameters in two protocols. In the first protocol, eight healthy men were studied at rest and during a single level of suhmaximal exercise. In the second protocol, seven healthy men were studied at rest and at progressively increasing exercise loads to tolerance. The changes in arterial blood gas levels, lactate, ~ R, Vo 2, Vco2, R, FET e o2 and f with exercise following marihuana smoking were no different than the changes with exercise alone. However, the level of exercise tolerance following marihuana smoking decreased by 5.5 minutes (range 0 to 19.5) compared to the level obtained without marihuana smoking. The difference in exercise tolerance was probably due to the additive effects of marihuana-caused tachycardia with exercise-caused tachycardia resulting in the obtainment of peak heart rate' with marihuana and exercise at a lower work level than with exercise alone.

Effects of Dopamine and Nitroprusside Infusion on Myocardial Infarct Size. Clayton Shatney; Dean MacCarter; Richard Lillehei, Minneapolis Systemic vasodilator therapy can reduce myocardial infarct size. Because of our observation that not all vasodilators are efficacious in cardiogenic shock, we examined the effects of dopamine and nitroprusside infusion on myocardial infarct size. Anesthetized mongrel dogs with similiar anatomy under-

42NO ANNUAL SCIENTIFIC ASSEMBLY 441

went ligation of the distal third of the LAD coronary artery. Dogs were then randomized into control and treatment groups. Treated dogs received a continuous IV infusion of: 6 j.£g/kg dopamine, 15 j.£g/kg dopamine, or sufficient nitroprusside to maintain BP 20 percent lower then preligation values. Animals were monitored six hours, sacrified, and the heart removed. The left ventricle (LV) was dissected free, weighed, sectioned, and incubated in nitroblue tetrazolium solution, an LDH stain. Unstained tissue (infarct) was dissected from the slices and weighed. Results will be given. By decreasing afterload, myocardial necrosis can be reduced. However, peripheral vasodilatation is not the sole factor affecting infarct size. Dopamine, which also has chronotropic and inotropic actions, was ineffective at 6 j.£g/kg and questionably beneficial at 15 ~/kg (hearts edematous and hemorrhagic). To reduce myocardial infarct size, treatment with a pure vasodilator is preferable to the use of an agent which is both a peripheral vasodilator and a strong cardiac stimulant.

Concepts Involved in Serial Vein Grafting Techniques in Coronary Artery Surgery. Richard T. Shore; James F. HoDman; W. Dudley Johnson, Miluiaukee

Our experience in serial (or snake) vein grafting stems from over 700 cases requiring four or more grafts to complete the revascularization of diffuse coronary occlusive disease. Certain patterns lend themselves to serial or snake grafting techniques. Primary use involves the left anterior descending coronary system where the distal graft is placed into the distal anterior descending coronary artery, and proximal anastomoses are formed to the distal branches of the anterior descending system. The second most common utilization is into the right coronary artery system where combinations are formed between a large distal right or posterior descending branch and through the proximal right coronary artery at the bifurcation. The circumflex coronary arterial tree is more difficult to plot, and frequently requires multiple grafts to complete revascularization. Principles of serial grafting include careful immobilization of anastomoses and securement of graft loops to the epicardium. The placement of an anastomosis to a totally obstructed vessel proximal to a graft of a vessel with minimal or modest gradient may form a "steal" with the competitive flow creating a situation conducive to obstruction of the proximal vein graft. The concern for late obstruction in these multiple graft systems is not borne out by the review of graft patency at one year postsurgery which shows a similar graft patency in both groups of either single or serial grafts.

Effect of Fiberoptic Bronchoscopy on Cardiac Rhythm. David L. Shrader; Darwin L. Peterson; Sambasiva Lakshminarayan, Seattle. Fiberoptic bronchoscopy (FB) may be associated with multiple arrhythmogenic stimuli. Forty-five patients had Holter monitoring prior to, during, and following FB. Arterial blood gases and serum lidocaine (X ylocaine) levels were measured during FB. Six patients had significant cardiographic changes during or post FB. None had prior history of cardiac disease. Three of these six patients had > 10 PVC/hr at baseline. Two other patients with ECG changes developed significant hypoxemia during FB. One patient who received epinephrine for acute bronchospasm following FB developed ventricular tachycardia. Xylocaine and theophylline levels were nontoxic in all subjects when measured. None of seven patients with

442 42ND ANNUAl SCIENTIFIC ASSEMBlY

positive cardiac histories had ECG changes with FB. Conelusion: 13 percent of patients developed ECG changes during or post FB. One-half of those patients could be identified as having> 10 PVC/hr at rest. Cardiac monitoring may be indicated for select patients during and postFB.

Serum Angiotensin Converting Enzyme and Lysozyme in Sarcoidosis. Jean Simonouiitz; Lillian Celie; David W. Cugell; Norman Solliday, Chicago Angiotensin-converting enzyme (ACE) and lysozyme (LE) were measured in 45 sarcoidosis patients, 28 normals and 45 patients with nonsarcoid diseases associated with pulmonary abnormalities including 28 with diffuse roentgenographic infiltrates. Thirteen of 45 sarcoid patients had an elevated ACE: 4/13 of stage (S) I; 5/8 S II; 4/ I I S III. Eight of 33 sarcoid patients had an elevated LE: 6/8 S II; 2/8 S III. ACE was increased in three nonsarcoid patients with interstitial fibrosis and two with miliary tuberculosis. In untreated sarcoidosis ACE and LE were correlated to each other (r 0.69 .01); ACE was inversely correlated to single breath difP fusing capacity (DL co ) in SI through IV (r - 0.46 P .05) and total lung capacity (TLC) in SII through IV (r - 0.51 .05); LE showed similar correlations (P .05). Serial P measurements up to 12 months after initiation of steroids showed a decrease in ACE and LE as DL co and TLC improved. ACE and LE may be useful adjuncts to DL co , TLC and roentgenograms in following sarcoid activity.

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Cytotoxic Drug-Induced Lung Disease: The Clinical Spectrum. H. Dirk Sostman; Richard A. Matthay; Charles E. Putman; G. J. Walker Smith; Carl E. Ravin, New Haven The records of 152 patients who received cytotoxic drugs were reviewed. Fifteen developed diffuse lung disease not due to infection, pulmonary malignancy or radiation. Seven had received methotrexate (MTX) , five bleomycin (BLE) , and one each busulfan (BUS), cytoxan (CYT) or 6-mercaptopurine (6MP). Patients with lung disease due to BLE, BUS, or CYT had all received large cumulative doses; MTX or 6MP pneumonitis did not appear dose-related. Symptoms included fever (12/15), dry cough (I 1/15) and dyspnea (10/15). Eosinophilia was present in three cases due to MTX. Chest radiographs showed diffuse nodularity and interstitial or mixed interstitial-alveolar patterns with MTX and 6MP; bibasilar, linear densities predominated with BLE, BUS and CYT. Pulmonary function studies showed hypoxemia, a restrictive ventilatory defect and decreased diffusing capacity for carbon monoxide with all drugs. Histopathology in seven cases revealed acute and organizing interstitial pneumonia with hyaline membranes, atypical epithelial proliferation, desquamation and nodular inflammation or fibrosis. In each case the offending drug was withdrawn; five patients recovered fully, eight developed chronic radiographic and/or pulmonary function abnormalities and two died of respiratory failure.

Reoperation for Occluded Coronary Artery Bypass Grafts: Improved V.ein Graft Patency with Platelet Suppressant Therapy. Peter Steele; George Pappas; Robert Vogel; James Anderson; Edward Genton, Denver Platelet suppressants have been reported to improve corona.ry artery bypass graft (CAB) patency. Fifteen men who had one or more CAB occluded had a second operation (one

CHEST, 70: 3, SEPTEMBER, 1976

early and no late deaths; average follow-up 16 months) and were treated with platelet suppressants. Platelet survival time (SURV) (51ch rom iu lll ) was shortened in all (2.3 ± 0.08 days; average ± SE~f; normal 3.7 ± 0.04 days; P 0.0(1) and platelet suppressant therapy (sulfinpyrazone in 12, clofibrate in 2, dipyridamole in I) increased SURV (2.7 ± 0.11 days; P < 0.(1) . After second operation, 30 of 34 (88 percent) grafts were patent, whereas five of 34 (15 percent) were patent after first operation. Of four men with an occluded graft after second operation. three had no increase of SURV with platelet suppressants. Of II men with all grafts open, 7 (64 percent) had an increase in SURV. Results suggest that SURV is shortened in patients with CAB occlusion, platelet suppressants lengthen SCR V and Inay prevent CAB occlusion.

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Effect of Nitroprusside on Myocardial Metabolism in Patients with Obstructive Coronary Artery Disease. Simon H. Stertzer; Nicholas P. Del'asquale; Michael S. Bruno; Nino D. Marino Neui York City i

Sodium nitroprusside (SNP) improves myocardial performance in pump failure as judged by hemodynamic pararneters, but little is known about the effect of SNP on myocardial metabolism in man. Accordingly, the influence of SNP on lactate balance and oxygen extraction was studied in 15 patients with ohstructive coronary artery disease. Control lactate balance was less than 20 percent in eight patients and negative balance was found in four patients. Following SNP infusion (25-100 ,ug/min) lactate balance improved in six patients, deteriorated in four patients, and did not change significantly in five patients. Lactate extraction shifted to production in two patients and from production to extraction in three patients. There were no consistent changes in myocardial oxygen extraction. There was no correlation between changes in lactate balance and hemodynamic estimates of left ventricular performance. Conclusion: improved left ventricular performance induced by SNP is not always associated with improvement in myocardial metabolism perhaps because of a "steal effect" associated with a redistribution of coronary blood flow. Pleural Effusion: A Diagnostic Dilemma. Donald D. Storey; David E. Dines; Douglas T. Coles, Rochester, Minnesota The etiology of pleural effusion in 108 of 133 patients was determined by laboratory values and clinical presentation; 25 were indeterminate even after a complete diagnostic evaluation. In 164 diagnostic thoracenteses, 136 cytologic examinations were performed. of which 20 (15 percent) were positive. Of 19 patients with bronchogenic cancer, 5 showed positive results to cytologic examination (26 percent); of 25 patients with metastatic cancer of the lung, 13 had positive results (52 percent); and of 20 patients with lymphoma, two had positive results (10 percent). Thirty-five of 105 (33 percent) patients had pleural fluid protein of <3 g/dl. Five of ~5 effusions with protein content of <3 g/dl were not classic transudates, and three of these five were secondary to malignant disease. Of 143 routine bacterial cultures, only five were positive (3 percent) . Of 103 mycobacterial cultures, only one was positive; of 76 fungal cultures, only one was positive. Despite the high incidence of indeterminate diagnoses, we recommend that only protein content and cytologic examination be ordered routinely. Our algorithm provides a logical and cost-effective approach to the diagnostic prohlem of pleural effusion.

CHEST, 70: 3, SEPTEMBER, 1976

Pulmonary Ya,Hl110Suke

Effects of Vinyl Chloride on Mouse Lung. Suzuki, lroing ]. Selikoi], New York City

Pulmonary effects of vinyl chloride were studied in 27 male mice (Charles river strain, four to five weeks old at first exposure) exposed to vinyl chloride monomer at various concentrations (2,500 ppnl and 6,000 pplll; five hours a day, five days a week) and durations (five months and six months) . PulInonary tumors were observed in 26 of 27 experimental animals. None was found in II control "lice. The tumors were multiple, round, whitish in color and variable in size from a fraction of a milfimeter to 2 mm. Histologically, these tumors were usually seen in the peripheral part of the lung parenchyma, and tended to he subpleural. They lacked a connective tissue capsule. '[he neoplastic cells were arranged in either papillary or adcnornatous formations. Polymorphism and atypical structure were not striking though mitotic division was occasionally found. No metastases to regional lymph nodes or to other organs were observed. In many respects, these tumors corresponded to "alveologenic tumor" or "alveologenic carcinoma.' From these findings, it is concluded that vinyl chloride has a neoplastic effect on mouse lung. Correlation of Right Atrial and Pulmonary Artery Wedge Pressures: Assessment of Value in Volume Expansion in Acute Myocardial Infarction and Non-Coronary Heart Disease. IHei'vin ]. T'onkon ; Ezra A. Amsterdam; Anth ony N. DeMaria; Martha Wood; Roberta Brocchini; Dean T. Mason, Davis, Cal. Controversy persists regarding the utility of right atrial pressure (CVP) as a guide to cardiac function and therapy in various clinical settings. Thus, simultaneous CVP and pulmonary artery wedge pressures (PA \V) were obtained in 24 patients. Fourteen patients with acute myocardial infarction (AMI) and ten patients with non-CAD left ventricular dysfunction (LVD) were studied before and after volume expansion (VE) with dextran. VE produced the following changes: AMI group - evp t80 percent (5 mm H~ -+ 9 mrn Hg) and PAW tlOO percent (8 mm Hg -+ 16 mrn Hg'); LVD group - CVP t50 percent (4 mm Hg -+ 6 mm Hg) and PAW 60 percent (10 mm Hg -+ 16 mm Hg). In all but two patients, both with severe chronic obstructive pulmonary disease, directional changes in CVP and PAW were parallel during VEe Thus, CVP correlates poorly with absolute value of PAW and does not reflect absolute magnitude of change with VEe However, it may be useful as a guide to directional and relative magnitude of change in PA'V during volume expansion in patients with AMI and non-CAD ventricular dysfunction with the exception of those with obstructive pulmonary disease. Effect of Chronic Hypertension on Maximal Stress Testing in Detection of Coronary Disease: Preserved Sensitivity and Specificity Determined by Comparison of Arterial Stenosis and Ventricular Wall Thickness in Coronary Patients with and without Hypertension. Melvin T'onkon; Richard R. Miller; Anthony De Marin; Jess Kraus; Nemat Borhani; Dean T. Mason, Davis, Cal Despite wide use of exercise testing (EXT) to detect coronary disease (CAD), effectiveness relative to major vessel (V) stenosis(S: 75 luminal narrowing) in chronic hypertension (HT) is unclarified. Thus, 35 HT patients undergoing maximal (M) EXT with CAD defined arteriographicallv (CA) were compared to 35 CAD patients hy CA without HT

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42ND ANNUAL SCIENTIFIC ASSEMBLY 443

matched for age, sex, CAD risk factors and VS. Computerized discriminant function analysis was performed. Positive MEXT was defined ~ 1.0 mm flat or downsloping ST depression .08 second after J point. +MEXT occurred in 25/35 (71 percent) HT patients and 22/35 (66 percent) CAD patients (P >.05). Total VS was 3.6 in HT vs 3.3 in CAD (P > .05); 16/20 (80 percent) HT patients with 3VS had +MEXT vs 17/21 (81 percent) CAD patients with 3VS (P > .05) . MEXT in HT vs CAD: ST segment -l- 1.6 vs 1.8 mm (P > .05); incidence of rvcs > 5/minute ('P > .05). Echographic left ventricular wall thickness (LVW): 1.17 an in HT vs 1.08 in CAD (P > .05) . In 11 patients HT subset with ECG left ventricular hypertrophy (LVH): LVW 1.29 and STJ, 1.9 m~ (P > .05 vs all HT patients) . There was no difference (P .05) in +MEXT in HT with LVH vs HT without LVH: 7~11 (63 percent) vs 18/24 (75 percent) . MEXT functional class and angina were same in HT vs CAD (P > .05) . Thus, MEXT is useful in detecting CAD in HT. However, there is no difference (P > .05) in sensitivity or specificity of MEXT in CAD with or without HT. In addition, LVH with HT does not affect MEXT identification of CAD.

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Airways response to Micro-Aerosolized Delta-9-Tetrahydrocannabinol. Louis Vachon; Arthur G. Robins; Edward A. Gaensler, Boston Marihuana and delta-9-THC, its principal psychoactive ingredient, decrease airways resistance in normal individuals and asthmatics. In previous studies, bronchodilation has been accompanied by substantial tachycardia and psychologic "high." In an attempt to dissociate these effects from bronchodilation, we administered a micro-aerosol of THC (0.7 mg) dissolved in propylene glycol. Seven normal subjects and ten asthmatics were tested with propylene glyol alone, with THC, and with isoproterenol. In asthmatics, THC decreased airways resistance (-16 percent at 90 minutes, P .05) and increased flow rates (FEV 1 + 9 percent, MMF + 22 percent, P .01) . Tachycardia from THC was not significant and no subject experienced more than transient "relaxation." Four subjects increased their airways resistance after vehicle alone; of these, two had no response to THC and two decreased airways resistance. We conclude that low-dose micro-aerosolized THC is an effective bronchodilator. Interestingly, some asthmatics but no normal subjects responded to the propylene glycol aerosol with increased airways resistance.

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CO 2 Threshold Ventilatory Responses in Asthmatic and Normal Subjects. John C. Vandree, and Archie F. Wilson, Irvine, Cal.

Occlusion pressures (P 100 ) and minute ventilatory (VE) responses to CO 2 were measured in eight asthmatic patients and compared to a group of normal subjects. ~E was characterized by two and th ree phase linear increases to increasing carbon dioxide with wide interindividual differences in the threshold of CO 2 at which phase increases occurred. P 10 0 also demonstrated wide interindividual differences in the threshold of CO 2 at which exponential increase occurred. No differences between the asthmatic and control groups were noted, although individual asthmatic patients either had very blunted response to carbon dioxide or had linear increases occurring only after end tidal CO 2 with 55 mm Hg. No difference in response in ~E or P 100 to increasing levels of CO 2 was noted in the asthmatic group after terbutaline. It is concluded that as a group, asthmatic patients respond like normal control patients in respiratory response to increasing

444 42NO ANNUAL SCIENTIFIC ASSEMBLY

levels of carbon dioxide but wide interindividual differences commonly occur. A subset of asthmatic patients with blunted response or high threshold to carbon dioxide may be at increased risk if respiratory insufficiency should occur. The Effect of Colloid Osmotic Pressure and Pulmonary Capillary Wedge Pressure on Intrapulmonary Shunt. Richard W. Virgilio; David E. Smith ; Charles L. Rice; Charles L. Hobelmann ; Christopher K. Zarins; David R . [ames; Richard M. Peters, San Diego Application of the Starling equation to fluid dynamics within the lung would suggest that a significant decrease in the gradient between the serum colloid osmotic pressure (COP) and pulmonary capillary wedge pressure (PC\VP) secondary to either an increase in PCWP or a decrease in COP would cause an egress of fluid from the capillary and an increase in the amount of pulmonary extravascular water (PEV\V). This should create intrapulmonary shunting (Qs/Qt) and produce hypoxia. The relationship between changes in this gradient (COP-PCWP) and Qsj Qt were studied in 43 patients (157 simultaneous determinations) following hemodynamic resuscitation with various fluids. The mean values (± standard error) and extremes for each of the variables were: PCWP 10.3 ± .04 mm Hg (0-30). COP 19.1 ± 0.3 mm Hg (8.4-27.6), COP-PCWP 8.7 ± 0.4 1l1n1 Hg (-10.6 -23.4) and Qs/Qt 15.6 percent ± 0.4 (7.4 - 26.3) . The slopes of all regressions between QsjQt and the other variables were not detectably different from zero. Marked decreases in COPPCWP (-10 mm Hg) secondary to hemodilution (COP 8.4 mm Hg) with crystalloid resuscitation failed to produce clinical evidence of increasing PEV\\,. Only two patients demonstrated pulmonary edema. both of whom had normal COP's but elevated PCWPs. Evidence from our animal laboratory would indicate that decreasing serum COPs are associated with increases in puhnonary lyrnph flow with minimal increase in PEVW. The lack of correlation between decreases in COP and increases in Qsj Qt suggests that the use of oncotic agents such as albumin during resuscitation to minimize pulmonary insufficiency is unwarranted. Effect of Morphine upon Hypoxic Ventilatory Response. Jonathan M. Ward, John V. Wei!, Denver Little is known of how morphine depresses respiration. This study examines the effect of morphine on hypoxic ventilatory drive at different levels of arterial Pco., and pH. In 12 urethane-anesthetized cats, 0.25 to 1.0 mg/kK morphine decreased the ventilatory response curve 30.1 ± 4.4 percent (P .01) by decreasing respiratory rate 27.5 ± 4.0 percent (P .01), with an insignificant fall in tidal volume of 2.8 ± 5.3 percent. Morphine significantly depressed the ventilatory response to hypoxia at constant levels of arterial Pco-, and pH of 38.0 ± 2.1 and 7.298 ± 0.019 by 47.3 ± 8.3 percent (p. .01). The response was similarly decreased by morphine despite hypercarbia of 44.5 ± 1.6 and pH of 7.247 ± 0.018 by 33.9 ± 4.7 percent (P .01). There was no significant difference in the response to hypoxia at the two different levels of Pcoj and pH. Thus. morphine significantly depressed hypoxic ventilatory response separate from Pco2 and pH effect.

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Identification of Potential Iatrogenic Infections Associated with Fiberoptic Bronchoscopy. Harold Weinstein; Roger Bone; William Ruth, Kansas City, Kansas With the increasing use of the fiberoptic bronchoscope (FB)

CHEST, 70: 3, SEPTEMBER, 1976

for diagnostic and therapeutic purposes. it is important to identify immediately any potential problems which would increase the otherwise low morbidity and mortality associated with its USt'. Based on our routine methods of obtaining and recording bacterial. fungal. and tuberculosis cultures from patients at the time of bronchoscopy. as well as periodic culturing of the FU itself. we were able to identify an index case of contamination of the FB with a Proteus species. Following initially unrecognized contamination of the FB, there were 12 subsequent bronchoscopies over a seven-day period; II bacterial cultures obtained by aspiration produced a Proteus species with similar sensitivities to the index case. Culture of the bronchoscope at the same time recovered an identical organism. Although we could not document febrile episodes or roentgenographic changes in these patients postbronchoscopy. the event necessitated revision of our usual FB sterilization procedures. We have therefore developed a protocol for culture collection. data retrieval. and FB sterilization which should serve to prevent potential outbreaks of FB related infection. Analogy Tests and Psychopathology at Follow-up after Open Heart Surgery. Allen E. Willner; Charles ]. Rabiner; B. George Wisofl; [irina Fishman ; Bernard Rosen; Marvin Hartstein; Donald F. Klein, Glen Oaks, New York A study of 100 coronary bypass and cardiac valvular surgery patients were investigated to determine whether preoperative brain damage. as measured by the Conceptual Level Analogy Test (CLAT). is a major risk factor for postoperative psychiatric symptoms and mortality. Three cognitive psychologic tests. including the CLAT. and psychiatric interviews were given preoperatively, postoperatively. and at 18-month follOW-Up. Surgical outcome was specified as: catastrophic outcome (death or severe stroke). psychiatric complications, or good outcome (survival with no psychiatric complications). Inhospital outcome related significantly to analogy test scores. as did both surgical procedure and diagnosis of rheumatic heart disease. However. long term outcome was unrelated to medical diagnosis and only weakly related to surgical procedure. but highly significantly related to preoperative analogy scores. The CLA'f was a more consistent predictor of both short and long term outcome than any of the other ten variables considered (medical and surgical variables. inhospital outcome. demographic measures. other psychologic tests). Flow-Volume Relationships in Obstructive and Restrictive Lung Diseases. Keith Wilson; Warren Miller; Thomas Blair; Paul Stevens, Houston The forced vital capacity (FVC) may be reduced with severe airways disease (ohstructive lung disease. OLD) , or as a result of disease processes which decrease lung volume without airways obstruction (restrictive lung disease. RLD) . Both of these processes may be associated with a decrease in absolute expiratory flow (VE). but in the presence of RLD. VE is decreased in proportion to the decreased lung volume (LV) . In the presence of a normal FVC, RLD is unlikely and OLD is identified by a decreased VEe However. if the FVC is reduced. it is difficult to determine whether VE is reduced due to the decreased LV, the airways obstruction, or both (combined lung disease, CLD) . To ascertain the degree of obstruction necessary to reduce the FVC, complete pulrnonary function studies of patients with clinically pure OLD were evaluated with regard to the magnitude of VE limitation as related to the reduction in

CHEST, 70: 3, SEPTEMBER, 1976

FVC. Similar analyses were performed for patients with clinically pure RLD. Among patients with OLD and a FVC 86 percent predicted. the VE was reduced much more than the FVC with a mean FEF :m-75/FVC ratio of 0.45. However, this relationship was not linear and among patients with a FVC of 50-86 percent predicted, the mean ratio was <0.5, while when the FVC was 20-50 percent predicted. the ratio was <0.3. Patients with pure RLD and an FVC <86 percent predicted had a linear relationship between FEF 25-75 and FVC with a ratio >0.8). Patients with a FEF :Ui-7a/FVC ratio between 0.45 and 0.8 were reviewed and 95 percent were found to have clinical. as well as physiologic evidence of CLD. We conclude that spirometric testing alone can identify patients with CLD without the need for more complete pulmonary testing.

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Combined Prednisone and Azathioprine Therapy for Interstitial Pneumonitis. Richard H. Winterbauer; Neely E. Pardee; Edward H. Morgan; John D. Allen, Seattle Seventeen patients with a diagnosis of diffuse interstitial pneumonitis established through open lung biopsy and clinical evidence of progressive disease received combined prednisone and azathioprine treatment. Prednisone was initiated in a dosage of 100 mg daily for two weeks. tapered to 20 mg daily over the ensuing six weeks and continued at this level for one year. Azathioprine (3 mg/kg/day to a maximum daily dose of 200 mg) was begun after three months of prednisone therapy and also continued for one year. Detailed pulmonary function tests were performed prior to treatment and repeated at three-month intervals through a mean 17-month follow-up. Eight patients showed striking improvement with therapy. The group demonstrated a rise in vital capacity from 2.04 L to ~.29 L and a rise in the resting Pa02 on room air from 61 to 75 mm Hg. Four of these eight patients have completed the treatment course and all have maintained their improvement off therapy four to 14 months. Five patients showed an arrest of disease progression with stable pulmonary function during therapy. and four patients demonstrated a progressive loss of function despite therapy. The three-month interval between the start of prednisone and addition of azathioprine provided some insight into the relative efficacy of the two drugs. Seven patients demonstrated improved pulmonary function during the initial three months of prednisone treatment with six of the seven showing further improvement with the addition of azathioprine. Only one patient who failed to respond to prednisone exhibited improveprovement with azathioprine. Intracardiac Repair of Tetralogy of Fallot in Adults: Report of 41 Patients. Don C. Wukasch; Luigi Chiariello; Joseph Meyer; George J. Reul, [r.; Grady L. Hallman; Denton A. Cooley, Houston Among 40~ pa tien ts undergoing total repair of tetralogy of Fallot during the past five years. 41 patients were over 21 years of age. These patients were evaluated to delineate optimal indications and timing for operation. and long-term results. Average age was 28 years in 21 men and 20 women patients. Palliative surgery had been performed previously in 58 percent of patients. Pressure gradient between the right ventricle and pulmonary artery averaged 84.5 mm Hg. Hospital mortality (14.6 percent) was greater in these adult patients than in the entire series (8.8 percent) . Causes of early death were congestive heart failure. pulmonary edema. bronchopneumonia. and associated mitral stenosis.

42NO ANNUAL SCIENTIFIC ASSEMBLY 445

Nonfatal complications included postoperative hemorrhage (17 percent) , and recurrent VSD (5 percent) . Two late deaths occurred (5 percent); one following reoperation for recurrent VSD and the other from congestive heart failure. Surgical considerations, and indications and timing will be discussed.

Oral Practolol as Adjunctive Therapy in Patients with Chronic Atrial Fibrillation. Joachim Yahalom; Herman O. Klein; Elieser Kaplinsky, Kjar-Saha, Israel In many patients with chronic atrial fibrillation, it IS Impossible to prevent excessive ventricular rate under stress even with toxic doses and high blood levels of digoxin. The effect of practolol on the heart rate at rest and low grade controlled exercise was investigated in 28 patients with chronic atrial fibrillation of various etiologies and in ten normal controls, who were all on maintenance dosages (0.25-0.75 mg) of digoxin. Practolol decreased the heart rate at rest from 99.8 beats per minute (bpm) to 77.5 bpm (23 percent reduction) and at mild exercise from 148 bpm to 105 bpm (29 percent reduction), P 0.01. The heart rate responses both at rest and during exercise in patients with atrial fibrillation receiving practolol and digoxin were identical to the ones in normals under digoxin alone. Fifteen patients had clinically significant heart failure. Practolol did not intensify their symptoms nor initiate hypotension. No serious side effects were detected. When digoxin therapy is not sufficient in the control of ventricular rate in chronic atrial fibrillation, the addition of the cardioselective practolol is recommended as adjunctive treatment of these patients.

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Atropine in Asthma with Predominant Small Airways Obstruction: Aerosol (Sch 1000) versus Intravenous. Noe Zamel, Michele Leroux, Toronto Five asthmatic men (aged 24-59) with the diagnosis of predominant small airways obstruction based on subnormal response of maximum expiratory flow (Vmax) breathing 80 percent helium 20 percent oxygen (He02) were selected.

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446 42NO ANNUAL SCIENTIFIC ASSEMBLY

Specific airways conductance measured by plethysmography (SGaw) was 0.047 ± 0.031 sec -lC1UH:!O-l and following salbutamol inhalation was 0.122 ± 0.072. Maximum expiratory flow volume curves were obtained using a body plethysmograph breathing air and repeated after 10 min of He02 breathing. We calculated at 50 percent vital capacity Vrnax on air C~' 50) and the difference of HeO:! over air as percent of air flow (~V;>o). SGaw, V;)() and ~ V 50 were measured in a control period and 60 min after three inhalations (GO ,ug) of isopropyl atropine (Sch 1(00) in one day and after 2 mg atropine sulfate IV in the next day. The results (mean ± SD) will be given. The increase of ~ V;>o is indicative of improvement of small airway obstruction which was more marked after Sch 1000 than after atropine IV. 'These patients had increased bronchomotor tone in small airways which was vagally mediated.

Ample Evidence That Proteins Participate in Pulmonary Surfacant. Kurt Ziinket; Peter Wendt; lVerrzer Tolle; Gunther Bliimel, Munich, Germany Although the precise composition of the alveolar surfactant is as yet not known, it is well established that a major component is dipalmitoyl lecithin (DPL); the role of proteins remains obscure. Lung washings of rats were centrifuged (I 05 ,OOOg, Ih) and the supernatant was subjected to gel filtration (1.5m Agarose). Surface active fractions, analyzed in a Wilhelmy-balance, were pooled and investigated for protein-DPL interactions with a newly developed binding test, using uniformly labelled 14C-DPL. Binding isotherms for protein ligands to 14C-DPL revealed one group of identical and independent binding sites. The binding of the label to protein diminished by trypsin incubation and is reversible by adding nonlabelled DPL to the incubation mixture. Surface pressure-area curves showed a dependence on the amount of pre-purified lung wash proteins, when applied to a subsolution of 30mM Na-Kphosphate, pH 7.4 and 22°C. The data strongly suggest that specific proteins, which are not serum contaminants, play an essential role in pulmonary surfactant system.

CHEST, 70: 3, SEPTEMBER, 1976

Cecile Lehman Mayer Research Forum Transthoracic Cryosurgery of Bronchopulmonary Structures: An Approach to Lesions Inaccessible to the Rigid Bronchoscope. Robert J. Carpenter, III; H. Bryan Neel, 1//; David R. Sanderson, Rochester, Minnesota

Transbronchoscopic cryosurgery is a less invasive alternate to surgery and may prove satisfactory for the treatment of selected patients with bronchopulmonary tumors. Transbronchoscopic treatment of upper lobe lesions is not possible with the present rigid cryosurgical probe. This study was designed to assess the feasibility of transthoracic cryosurgery of upper lobe bronchi. In eight dogs the right upper lobe bronchus was identified, and a I cm diameter cryoprobe at -1f>O°C was applied to the serosal surface. The crvolesion extended from the origin of the right upper lobe bronchus to its trifurcation. Time-temperature relationships were assessed using needle thermocouples. In 12 other dogs, a 3 ern longitudinal bronchotomy was made in the right" upper lobe bronchus. In eight of these dogs, a 6 mm diameter cryoprobe was inserted through the bronchotomy into each peripheral bronchus. These freeze-thaw cycles were employed in. each area. including the margins of the bronchotomy. Four control dogs had bronchotomy only. All dogs survived. Mucosal temperatures adjacent to the probe tip reached a mean of _60°C in 120 seconds. Necropsies were performed 1,7, 14, 30,60, 90, and 180 days postoperation for gross and histologic examination, There was early complete necrosis of mucosa and glandular structures in the target sites. By 14 days, the target was covered with cuboidal epithelium. Normal ciliated epithelium was present by 180 days. Cartilage remained intact. There was no stricture formation or impairment of healing. Cryonecrosis of bronchi may be safely induced by application of the cryoprobe to serosal surfaces, or, under direct vision to mucosal surfaces through a bronchotomy. Transthoracic cryosurgery may reduce the necessity for surgery in selected patients with bronchopuhnonary tumors inaccessible to the genic tumors have been palliated by the transbronchoscopic rigid bronchoscope. Eight patients with recurrent bronchoroute.

The Effects of a Hair Spray Aerosol on Tracheal Mucociliary Transport in Humans. Mitchell Friedman; Richard Dougherty; Steven. R. Nelson; Robert P. White; Maroin A. Sackner; Adam Wanner, Miami Beach

The acute effects of a 20-second exposure to a commercially available aerosol hair spray preparation on pulmonary function and tracheal mucociliary transport were evaluated in seven healthy, seated nonsmokers. Five subjects exposed to a Freon propellant mixture alone served as controls. Pulmonary function tests consisted of expiratory flow-volume curves, spirornetrv, specific airway conductance, and single and multiple breath nitrogen washout curves. Tracheal nlUCOUS velocity was estimated by a new roentgenographic method that utilizes discs of Teflon mixed with bismuth trioxide as a marker. These discs were deposited on the tracheal mucosa and the linear velocities measured from videotape recordings of the fluoroscopic disc image. Physiologic measurements were made before and serially for three hours following either hair spray or Freon exposure. No significant changes occurred in the pulmonary function tests

CHEST, 70: 3, SEPTEMBER, 1976

after exposure to hair spray or Freon propellant. Mean tracheal mucous velocity (± SD) decreased significantly by 70 percent one hour following exposure to hair spray (10.2 ± 1.1 mm rrnin to 3.1 ± 5.7 mrn/rnin. Also, caudal movement of the discs were observed in two subjects. The values returned to baseline by the end of the three-hour period. Tracheal mucous velocity did not significantly change after exposure to Freon alone. Thus, acute exposure to aerosol hair spray produces a transient impairment of an important pulmonary defense mechanism. Repeated exposures may produce adaptation or airway damage which should be considered in the evolution of chronic obstructive lung disease. It is also apparent that respiratory effects of commonly used aerosol products may not be detected by conventional pulmonary function testing.

Role of Vasoactive Substances in the Pathogenesis of Respiratory Distress Syndrome. Scott Lerner; John Wolfe; Roger Bone; Daniel Stechschulte; Jerry Hood; Everett Murphy; Richard Sobonya, Kansas City, Kansas

The pathogenesis of the adult respiratory distress syndrome is unknown. In order to study the role of vasoactive mediators in this syndrome, a canine model of acid-induced pneumonitis was used. Eighteen experimental animals (Exp) received tracheal instillation of 3 ml/kg of 0.1 N hydrochloric acid, while seven control animals (Cont) received an equal volume of normal saline solution. This technique produced the following statistically significant (P<0.05) changes after acid instillation: I) decreased heart rate at 10 minutes (Cont 130 ± 15; Exp - 82 ± 10); 2) decreased arterial pH at 60 minutes (Cont - 7.41 ± 0.01; Exp - 7.18 ± 0.02); and 3) decreased effective static compliance at two hours (Cont - 37 ± I ml rcm H 2 0 ; Exp 21 ± I mlj crn H 2 0 ) . Serial plasma samples from II animals (10 Exp; I Cont) were assayed for slow reacting substance (SRS) and those from 21 animals (18 Exp; 3 Cont) were assayed for histamine (H). SRS was defined as guinea pig ileum smooth muscle contracting activity unaffected by histamine and acetylcholine antagonists, adsorbable on amberlite XAD-8 and sensitive to aryl sulfatase. Activity was detected in the plasma of 2/10 Exp animals. No plasma activity was found in the control. Pretreatment of animals with either H 1 (Mepyramine) or H 2 (burimamide) histamine receptor antagonists had no effect on the physiologic changes observed. Thus, acid-induced pneumonitis is associated with predictable pulmonary physiologic changes, transient increases in the circulating levels of histamine base and generation of a substance/substances which are nonacidic in nature, but capable of mimicking the acid-induced physiologic changes.

The Regulation of Airway Caliber in Healthy Subjects. Michael R. Littner; E. Neil Schachter; Arend Bouh uys, New Haven

Animal models have demonstrated that airway smooth muscle is constricted by beta adrenergic blockade and relaxed by phosphodiesterase inhibition. In addition, pretreatment with propranolol (P) potentiates and theophylline inhibits histamine (H) and acetylcholine induced airway constriction. In order to determine the applicability of such models to

42ND ANNUAL SCIENTIFIC ASSEMBLY 447

healthy subjects (HS) we obtained (in HS) linear dose-response curves to microaerosolized H and methacholine (M). Flow rates were measured with partial expiratory flow-volume curves at 60 percent of the vital capacity below total lung capacity (MEF4o (p) ) . A group of 8 HS was pretreated with single oral doses of 80 mg of P and placebo and the airway responses to H compared. A second group of seven HS was pretreated with single oral doses of 300 mg aminophylline (A), 400 mg cannabinoid bronchodilator (C), and placebo on separate days. The modification of the airway responses to H and M (separate days) by placebo, A and C was compared. Propranolol compared to placebo significantly augmented the decrease in MEF40 (p) induced by H without changing the threshold response. Aminophylline, when compared to placebo, did not protect against H or M, but C did so significantly. MEF40 (p) values were not significantly different two to three hours after pretreatment with P, A or C when compared to placebo. We conclude that in addition to similarities, there are distinctive differences in the regulation of airway caliber in HS from that predicted on the basis of experimental models. An Animal Model for Immune Complex Pulmonary and Renal Disease in Heroin Addicts. W. R. Smith; F. L. Glauser; L. C. Dearden; I. D. Wells; H. S. Novey; A. F. Wilson; D. M. McRae; D. Smeltzer; P. Egan, Irvine, Cal. The etiology of pulmonary edema, sudden death, ventilation perfusion abnormalities, and immune complex of glomerulonephritis in heroin addicts has remained obscure. We

448 42NO ANNUAL SCIENTIFIC ASSEMBLY

found, in addicts' sera, precipitating antibodies against several fungi, including Aspergillus species, A-I faeni, and T vulgaris (JAMA 232:1337, 1975). Also, we described decreased levels of IgM and C3 complement in the sera of addicts with heroin lung (Chest 68:651, 1975). Others cultured a variety of microorganisms (including Aspergillus) from street heroin. Subsequently, we demonstrated deposits of IgM, IgG, IgA, and C3 complement bound to lung tissue -of six addicts who died with heroin lung. We felt that contaminants in street heroin, specifically fungal organisms associated with hypersensitivity pneumonitis and allergic bronchopulmonary aspergillosis, might be responsible for these pulmonary abnormalities. Therefore, daily we injected, intravenously, ten rabbits with street heroin, six rabbits with USP-reference standard heroin, six rabbits with sterile saline, and eight rabbits with extracts of Aspergillus niger. At sacrifice, four street heroiit rabbits had immunofluorescent deposits of IgM, IgG and C3 complement in their pulmonary parenchyma and renal tissues, whereas saiine controls and USP-reference standard animals were negative. Four of the Aspergillus niger rabbits had deposits of IgM, IgG and C3 complement in their pulmonary parenchyma. In the immunofluorescent-positive lungs, electron microscopy showed increased basement membrane thickness, collagen deposition, fibroblastic proliferation and "activated" leukocytes. We conclude that the contaminants in street heroin, especially Aspergillus species, can lead to immune complex pulmonary disease. Whether these microorganisms are responsible for pulmonary edema and sudden death requires further study. .

CHEST, 70: 3, SEPTEMBER, 1976