Edward E. Lawson

Bronchopulmonary dysplasia: Possible relationship to pulmonary edema

The pathogenesis of bronchopulmonary dysplasia is controversial. Oxygen toxicity, mechanical trauma to the lung secondary to respirator therapy, and congestive heart failure with a left to right shunt through a patent ductus arteriosus have all been implicated. Our data suggest that in addition to these three conditions, all of which are edemagenic, infants with bronchopulmonary dysplasia have a significantly greater mean fluid intake in the first five days of life when compared with infants with respiratory distress syndrome or patent ductus arteriosus alone. We suggest that the addition of a fluid load may potentiate the effects of other factors and increase the risk of bronchopulmonary dysplasia in infants with respiratory distress syndrome who require respiratory support.

Saturated Phosphatidylcholine in Amniotic Fluid and Prediction of the Respiratory-Distress Syndrome

The lecithin/sphingomyelin (L/S) ratio in amniotic fluid is widely used to predict the risk of respiratory-distress syndrome. However, the results are unreliable if the specimen is contaminated or obtained during a complicated pregnancy. We therefore compared the predictive value of the L/S ratio with that of the concentration of saturated phosphatidylcholine (SPC) in 322 amniotic-fluid samples, 75 per cent of which were contaminated or obtained during complicated pregnancies or both. A positive result is one that predicted the development of respiratory-distress syndrome, taken as an L/S ratio equal to or less than 2/1 or an SPC below 500 mug per deciliter. The respiratory-distress syndrome was correctly predicted in 25 of 45 cases (55.5 per cent) with L/S ratios equal to or less than 2/1, and in 35 of 42 cases (82 per cent) with SPCs less than 500 mug per deciliter. When L/S ratios were greater than 2/1, there were 13 of 277 (4.7 per cent) false negatives, and when SPCs were above 500 mug per deciliter, there were three of 280 (1.1 per cent) false negatives. We conclude that determination of SPC is both more specific and more sensitive as a predictor of the respiratory-distress syndrome than the techniques currently in use.

Electrical potential difference and ion transport across nasal epithelium of term neonates: Correlation with mode of delivery, transient tachypnea of the newborn, and respiratory rate

We studied the change in ion transport function by measuring the basal transepithelial potential difference (PD) across the ciliated epithelium of the nose in 85 term neonates during the first 72 hours of life. Differences in PD associated with the mode of delivery or the presence of respiratory disease and differences in the PD response to the superfusion of amiloride (10(-5) mol/L) were assessed. We also studied term neonates with transient tachypnea of the newborn (TTN) and acute respiratory insufficiency. Basal PDs during the first 24 hours of life were higher in neonates delivered by cesarean section without prior labor (-29.7 +/- 2.5 mV) and in those with TTN (-38.5 +/- 6.0 mV) than in neonates born during normal spontaneous vaginal delivery (-23.0 +/- 2.9 mV) or cesarean section with prior labor (-23.7 +/- 0.7 mV) or in those with respiratory insufficiency (-22.4 +/- 2.3 mV). The percentage inhibition of PD by amiloride superfusion (less than 24 hours) was significantly lower in infants with TTN (30.9 +/- 4.9%) and after cesarean section without prior labor (31.8 +/- 2.2%) than in other groups (37.6 +/- 1.6%). By 48 hours, nasal PDs after cesarean section without prior labor and in neonates with TTN had declined; and by 72 hours, values were similar to those in other groups; respiratory rate paralleled the decline in PD. The respiratory rate of neonates with respiratory insufficiency remained high and paralleled the persistence of respiratory distress. Amiloride sensitivity was similar for all groups by 72 hours. These findings indicate (1) that PDs vary with the mode of delivery and support a role for labor in the normal transition of respiratory epithelial ion transport and (2) that TTN is associated with abnormal epithelial ion transport.

Augmentation of Pulmonary Surfactant Secretion by Lung Expansion at Birth

Summary: To study the effect of lung expansion at birth on surfactant secretion, we delivered by hysterotomy 11 litters of rabbit pups at 30 days of gestation and divided them into three groups that were killed: 1) after 30 min air-breathing, 2) after 30 min nitrogen-breathing, and 3) after 30 min tracheal occlusion. Each group was compared to a littermate group killed at birth. Groups 2) and 3) continued respiratory efforts for 30 min despite progressive asphyxia. Six additional litters were pretreated with atropine; at delivery one-half of each litter was killed, the remaining pups were subjected to 30 min of hypoxic gas breathing. After sacrifice, alveolar surfactant was recovered by saline lavage and estimated quantitatively on a surface-tension balance. Surfactant concentration at birth was 1.40 ± 0.22 mg/g dry lung and increased to 1.86 ± 0.19 (± SEM) after 30 min air-breathing (P < 0.01). Also, surfactant was increased in the nitrogen-breathing pups (from 1.61 ± 0.35 in littermate controls to 2.41 ± 0.58; P < 0.03), but not to a significant degree in the occluded group (1.34 ± 0.33 vs. 1.41 ± 0.28), or the atropine pretreated breathing pups (1.77 ± 0.29 vs. 1.89 ± 0.25).Speculation: The data indicate that lung expansion at birth enhances surfactant release from intracellular sites and suggest that the vagus nerve mediates this effect. It is possible that the effect of maternal atropine may have clinical significance in preterm infants.

Neonatal pneumopericardium: Current management

Neonatal pneumopericardium (PPC) is a frequently encountered complication of ventilator therapy. However, the appropriate management remains controversial. We describe seven infants who demonstrate the clinical spectrum of PPC. It is apparent that PPC can occur as an asymptomatic finding and may not require invasive therapy. PPC may present also with cardiac tamponade and require immediate diagnosis and therapy. Simple needle pericardiocentesis is appropriate therapy for most cases with tamponade, however a few babies with PPC uncontrolled by needle aspiration required placement of pericardial catheter for continuous drainage of the air. Mortality from PPC with tamponade (86% without therapy) should be much improved with modern management.

Radionuclide diagnosis of infradiaphragmatic total anomalous pulmonary venous drainage

SummaryWe hypothesized that infradiaphagmatic total anomalous pulmonary venous drainage (ITAPVD), because of its unique physiology, could be diagnosed with radionuclide angiography. Seven neonates with severe respiratory distress were injected intravenously with 3 mCi technetium-99m pertechnetate. In each of four neonates demonstrated to have ITAPVD by pulmonary angiography, nuclide recirculation through the right atrium occurred 3–6 s after initial passage. In addition, direct visualization of the anomalous common pulmonary trunk with nuclide as a “tail” below the diaphragm was obvious in the third infant studied. This prompted review of the first two infants with ITAPVD; in retrospect the anomalous trunk was also visualized with nuclide in both of these infants. All three were injected via the upper extremity. In the fourth ITAPVD infant, nuclide was injected via the lower extremity. In that infant, preferential streaming of the inferior vena caval flow and nuclide across the foramen ovale into the left heart led to simultaneous opacification of anomalous trunk and descending aorta, obscuring the “tail” sign.

Delayed lung maturation in fetuses of alloxan diabetic rabbits

Maternal diabetes has been associated with an increased incidence of hyaline membrane disease. We have studied this relationship in rabbit does injected with alloxan and then mated. A total of 26 litters were studied. Fetuses from saline-injected control and diabetic litters were examined at 27.5 and 29.5 days gestational age. Pressure-volume curves were performed and surfactant from alveolar lavage fluid was quantified on a surface balance. Blood sugars of diabetic does ranged from 175-400 mg/dl throughout pregnancy as compared with 80-120 mg/dl in the controls.We conclude that fetuses of diabetic rabbits have less deflation stability and quantitatively less surfactant when born prematurely but these effects are diminished close to term.

1203 NEUROGENIC MEDIATION OF AUGMENTED SURFACTANT SECRETION AT BIRTH

The observation that alveolar lavage surfactant increases at birth following air or nitrogen breathing suggests that lung expansion affects net surfactant secretion (Ped Res 11:574, 1977). To study the mechanism of secretion we treated 13 pregnant rabbit does at 30 days gestation with repeated infusions of atropine (total, 2.4mg IV) or propranolol (total, 3-10mg IV) over a ½ hour period immediately prior to sacrifice. The pups were delivered by hysterotomy and divided into two groups. One group was sacrificed at birth without breathing. The remaining pups were sacrificed after 30 minutes hyperventilation induced by hypoxia (10-15% O2) or anoxia. Following sacrifice, alveolar surfactant was recovered by saline lavage and quantitatively estimated on a surface-tension balance (Science 169:603, 1970).These results provide additional support for the hypothesis that pulmonary surfactant secretion is stimulated following the onset of gas ventilation in newborns. We conclude that augmented surfactant secretion at birth is mediated by a neural mechanism. Furthermore, since the secretion is blocked by atropine and not propranolol we suggest secretion is under cholinergic control.

233 INCREASED FETAL BREATHING WITH PILOCARPINE IN FETAL LAMBS

Rapid irregular fetal breathing (FB) is present 35% of the time in the fetal lamb and 70-80% of the time in the human fetus near term. Several pharmacologic agents affect FB patterns. CNS stimulants, such as epinephrine, doxapram, and caffeine,increase fetal breathing, while depressants, such as phenobarbitol, depress it. Pilocarpine (PC), a cholinergic drug, has known CNS excitatory action. To study the effect of PC (3 mg/kg fetal weight) on FB, tracheal pressure(TP) was monitored in three chronically catheterized fetal lambs between 139 and 147 days gestation. Drugs were infused directly into the fetal jugular vein.The effect of PC on FB may be mediated through one of two mechanisms or both: the short latent period suggests a direct cholinergic mechanism; the longer latency seen in atropine pretreated fetuses resembles that of epinephrine, consistent with a nicotinic action at the sympathetic ganglia.

EVIDENCE THAT ENDORPHIN (S) MODIFY THE RESPIRATORY RESPONSE TO NEONATAL ASPHYXIA

Endorphins are endogenous polypeptides with morphine-like activity which are widely distributed in the central nervous system and bind to opiate receptors. They presumably function as inhibitory neurotransmitters in pain pathways. We tested the hypothesis that endorphins modified the respiratory response to asphyxia in newborn rabbit pups (3-5 days of age). Pups from the sane litter were injected I.P. with either 1 ml saline or 1 ml (0.4mg) naloxone, a specific endorphin antagonist. Five minutes later asphyxia was produced by tracheal occlusion and maintained until gasping resumed after primary apnea. Four occlusions were done on each pup and 3 minutes allowed for recovery between occlusions. The time to primary apnea increased by 20% from 44.2±1.5 (S.E.) sec in saline pups to 52.9±1.9 sec in naloxone pups (p<.001) while the duration of primary apnea decreased by 60% (45.5±11.1 vs 18.3±2.0 sec) (p=.01). The tracheal pressure achieved during the first gasp following primary apnea was identical in saline and naioxone pups (54.2±2.7 vs 54.3±2.5 cm H2O). Naloxone acts by competitive blockada of opiate (endorphin) receptors. These data therefore provide evidence that endorphins modify the respiratory response to asphyxia by decreasing the frequency of respiratory center discharge but do not appear to decrease the amplitude of the respiratory center output at the time of the first gasp.