to better understand mechanisms that control pulmonary vascular tone and reactivity in the fetus, the authors infused tolazoline either continuously or as bolus into the left pulmonary artery of 15 chronically instrumented normoxic fetal lambs during late gestation. The vasodilatory effects of bolus injections of tolazoline (2.5 mg) were inhibited by the prior administration of the histaminergic receptor blockers, cimetidine (56%), diphenhydramine (56%), or both (100%). During the continuous infusion of tolazoline (4.5 mg/h for 9 minutes), pulmonary blood flow to the left lung increased from 61 _+ 6 mL/min (mean .+ SE, control) to 100 _+ 10 (peak) at 30 minutes (P < .001). However, following this initial vasodilatation, pulmonary blood flow steadily decreased toward control values by 90 minutes, despite the continued infusion of tolazoline (P < .001). Although the calcium channel blocker, verapamil, and the c~adrenergic blocker, phentolamine, had little effect on fetal pulmonary blood flow when infused alone, both drugs increased the vasodilatory response to tolazoline (P < .001). The authors conclude that tolazoline affects pulmonary vasodilation by a histaminergie mechanism and that subsequent refractoriness to the drug is a calcium-dependent process that may be partially mediated by an c~-adrenergic mechanism.--Prem Puri Extracorporeal Membrane Oxygenation for Newborn Respiratory Failure. T.R. Weber, D.G. Pennington, R. Connors, et al. Ann
Thorac Surg 42:529-535, (November), 1986. Extracorporeal membrane oxygenation (ECMO) is being used with increasing frequency to treat neonatal respiratory failure. Twenty-two newborns were treated with ECMO for 41 to 310 hours and 15 survived. Complications occurred in many of the patients and included seizures (8), renal failure (5), bleeding (4), and neurologic deficits (3). Sepsis was a major complication contributing significantly to mortality. One to 18 month follow-up finds 12 of 15 children surviving with normal neurologic examination. The series supports others in the literature that show convincingly that ECMO is an effective modality for the treatment of what would otherwise be fatal respiratory failure.--Marleta Reynolds Extraeorporeal Membrane Oxygenation (ECMO) in Neonatal Respiratory Failure: 100 Cases. R.H. Bartlett, A.B. Gazzaniga, J. Toomasian, et al. Ann Surg 204:236-245, (September), 1986.
The authors present a continuing follow-up of their experience with the use of extraeorporeal membrane oxygenation (ECMO). This report details clinical trials of 100 consecutive infants treated for respiratory failure. The patients were studied in three phases. Phase I included patients in whom all other therapy had failed and the attending neonatologist considered the infant moribund. The purpose of this group was to evaluate the safety and efficacy of ECMO. Phase II involved a prospective controlled randomized evaluation in which ECMO was compared with conventional ventilation. In Phase III, ECMO was used for all patients with an expectant mortality risk of 80% or greater. Seventy-two of the 100 patients studied survived: Phase I, 27 of 50 (54%); Phase II, 27 of 30 (90%); and Phase III, 18 of 20 (90%). Diseases treated included meconium aspiration syndrome (44), respiratory distress syndrome (26), persistent fetal circulation (10), congenital diaphragmatic hernia (9), sepsis (8), and other (3). Average time of therapy was 93.2 hours (range 1 to 265 hours). Bleeding was the most common complication and was treated with lowering the systemic heparin dose and providing platelets, Twenty-nine patients suffered intracranial bleeding with the highest rate being in premature infants <35 weeks gestational age (89%). Hypoxic cardiac arrest occurred in four patients during cannulation; none died. Follow-up was from 3 months to 11 years. Forty-five (63%) are normal or near normal, 12 (17%) suffer major neurologic dysfunction, and eight show pulmo-
nary dysfunction requiring supplemental oxygen at discharge. The technique of ECMO is briefly reviewed and a comparison made with operating room cardiopulmonary bypass. The technique offers advantages as to the site of cannulation (neck), the ability to cannulate prior to anesthesia thereby avoiding hemodynamic instability, the absence of a reservoir and direct gas interfaces, and a decreased need for anticoagulation and hypothermia. The authors conclude that almost all respiratory failure in infants over 34 weeks gestation is reversible and that ECMO offers a treatment alternative for those patients who have reached a high mortality risk with conventional treatment. ECMO circumvents the damaging effects of mechanical ventilation, and bypass support allows the resolution of functional transient pulmonary hypertension (the underlying mechanism of respiratory failure in these patients).--Edward G. Ford Oligohydramnios-lnduced Lung Hypoplasia: The Influence of Timing and Duration in Gestation. A.C. MoesMnger, M.H. Collins, W.A. Blanc, et al. Pediatr Res 20:951-954, (October), 1986.
The authors drained amniotic fluid for periods of five and ten days at various times in gestation between days 40 and 55 in the guinea pig (term is 67 days). They analyzed the impact of this procedure on fetal lung growth and used untouched littermate fetuses as controls. During the canalicular stage of lung development, total lung DNA per gram of fetal weight was significantly reduced after only five days of oligohydramnios, and the percent change did not vary between the two consecutive five-day periods studied (period A, days 40 to 45, SD of -0.047 rag, P = .004; period B, days 45 to 50, SD of -0.042 mg, P = .002). The impact of the same duration of oligohydramnios on lung growth later in gestation during the terminal sac stage of lung development was less (period C, days 50 to 55, SD of -0.027 mg, P = .097). This reduction in effect between period A or B and C was significant at the 0.05 level using a one-way analysis of variance. Two overlapping ten-day periods were also studied. In both experiments, the percent changes in lung DNA per gram of fetal weight between experimental and littermate controls were significant (period D, days 40 to 50, SD of -0.072 mg, P = .001; period E, days 45 to 55, SD of -0.047 mg, P = .001). The inhibitory effect of oligohydramnios on lung growth was more marked in period D than E (significant at the 0.05 level). A two-way analysis of variance indicated that the magnitude of the changes was related to both the time of onset and the duration of oligohydramnios. The authors conclude that even a short period of oligohydramnios interferes with lung development, and that the extent of this interference depends to a large extent on the time of onset and to a lesser extent on the duration of oligohydramnios. Irrespective of duration, the greatest effects were observed during the canalicular stage of lung developm e n t . - - P r e m Puri Morphometry of Hypoplastic Fetal Guinea Pig Lungs Following Amniotic Fluid Leak. M.H. Collins, A.C. Moessinger, d. Kleinerman, et al. Pediatr Res 20:955-960, (October), 1986.
Deficient quantity of amniotic fluid causes fetal guinea pig lung hypoplasia. Oligohydramnios that lasts only five days in early gestation is sufficient to reduce fetal lung growth significantly. The authors quantitated lung structural alterations at 50 days gestation (term is 67 days) of fetal guinea pigs whose amniotic fluid was drained on day 45 gestation. The study period spans the late canalicular, early saccular phases of guinea pig lung growth. Compared with littermate controls (n = 4), experimental fetuses (n = 5) have reduced lung to body weight ratio (2.81 +_ 0.16 v 3.21 • 0.20 x 10 -2, P < .01), indicating lung hypoplasia. Lung volume is significantly decreased in the experimental fetuses. (1.17 ,+ 0.15 v 1.34 ,+ 0.07 mL, P < .05). The proportion of lung containing parenchyma (ie, developing alveoli and alveolar ducts) is