SummaryTo 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 nitrogenbreathing, 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 f 0.19 (k SEM) after 30 min air-breathing (P < 0.01). Also, surfactant was increased in the nitrogen-breathing pups (from 1.61 , f 0.35 in littermate controls to 2.41 f 0.58, P < 0.03), but not to a significant degree in the occluded group (1.34 + 0.33 vs. 1.41 k 0.28), or the atropine pretreated breathing pups (1.77 + 0.29 vs. 1.89 + 0.25). SpeculationThe 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.Studies with newborn rabbits have shown that the percent of acetone precipitable lecithin in pulmonary lavage (12), pulmonary stability (29), and pulmonary lavage phospholipid content (25) increase after birth. These findings indicate that immediately after birth the secretion of surfactant into the alveoli is increased over and above the fetal secretion rate. With the onset of breathing, augmented surfactant secretion may be due to mechanical, neuronal, or humoral factors. Both lower surface tension and increased saturated lecithin in alveolar wash result from constant air-expansion of excised adult dog lungs (8), a mechanical stimulus. In rabbits, fetal injection of pilocarpine or P-adrenergic stimulants (e.g., isoxsuprine) also result in increased alveolar surfactant (5,6,7,18,30). These pharmacologic effects suggest autonomic control of surfactant secretion.To determine the physiologic stimulus for increased alveolar surfactant after birth, we measured quantitatively the surfacebreathing and the occluded pups differentiate the effects of asphyxia with and without gas ventilation of the lungs. The findings in the atropine pretreated groups establish that neural factors mediate surfactant secretion at birth. MATERIALS AND METHODS ANIMAL PROCEDURESTwenty litters of New Zealand white rabbits were used. The gestation of each litter was known to be 30 days within 3 hr (term = 31 days). In 11 litters, the does were sacrificed immediately before laparotomy with an iv infusion of 300 mg pentobarbital. Within 2 min, all the pups of a litter were gently delivered within their amnioti...