Abstract 1819 Pulmonary: Control of Breathing Poster Symposium, Tuesday, 5/4

Evidence suggests that vagal innervation is critical for the maintenance of continuous breathing and gas exchange during the neonatal period. Our group has recently shown that fetal lambs which have undergone vagal denervation prenatally manifest increased minimum surface tension, perivascular edema, partial atelectasis and develop respiratory failure or do not establish adequate alveolar ventilation shortly after birth (J. Appl. Physiol. 85:849-859,1998). In these studies, however, vagal denervation was performed prenatally and it is not clear whether the deleterious effects of vagal denervation on the surfactant system and respiratory drive were of prenatal origin or due to the lack of postnatal vagal feedback. To quantify the relative roles of prenatal vs. postnatal vagal denervation on control of breathing, we studied 14 neonatal lambs; six were sham operated, whereas eight were vagally denervated. To avoid laryngeal muscle paralysis, vagal denervation was performed intrathoracically below the origin of the recurrent laryngeal nerves. Each animal was instrumented within 24 h of birth to record electrocorticogram (ECoG), electro-oculogram (EOG), nuchal and diaphragmatic electromyograms, heart rate, blood pressure, esophageal pressure, and rectal temperature. ECoG, EOG and nuchal electromyogram were used to define various sleep states. By 24 hours post operatively, all denervated animals developed respiratory failure, whereas the sham operated animals maintained normal breathing patterns and pulmonary gas exchange (P<0.001). Expiratory time significantly increased in denervated animals as compared to the sham operated group(3.4±0.3 and 1.3±0.34 sec., respectively). In contrast to sham-operated lambs, vagally denervated animals had a decreased respiratory rate (37±1 vs. 15±1 breaths/min.), minute ventilation (439±196 vs. 271±96 ml/min./Kg) and lung compliance (14±5 vs. 5±1 ml/cmH2O) (sham-operated vs. denervated group, respectively. ANOVA; P≤ 0.02). Incidence of rapid, and non-rapid eye movement sleep and arousal states were similar in sham and denervated groups. No significant differences were observed in lung histology (light and electron microscopy), total phospholipids, large and small surfactant aggregates or surface activity of the bronchoalveolar lavage between the sham operated and vagally denervated animals. We provide new evidence that 1) postnatal as opposed to prenatal vagal denervation does not affect the surfactant system and 2) pulmonary vagal feedback is critical in the maintenance of respiratory drive during early neonatal period.

Funded by The Medical Research Council of Canada