Changes in respiratory timing induced by hypercapnia in maturing rats

Departments of 1 Pediatrics, 2 Medicine, and 3 Anatomy, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106 Premature infants respond to hypercapnia by an attenuated ventilatory response that is characterized by a decrease in respiratory frequency. We hypothesized that this impaired hypercapnic ventilatory response is of central origin and is mediated via -aminobutyric acid-ergic (GABAergic) pathways. We therefore studied two groups of maturing Sprague-Dawley rats: unrestrained rats in a whole body plethysmograph at four postnatal ages (5, 16-17, 22-23, and 41-42 days); and ventilated, decerebrate, vagotomized, paralyzed rats in which phrenic nerve responses to hypercapnia were measured at 4-6 and 37-39 days of age. In the unrestrained group, the increase in minute ventilation induced by hypercapnia was significantly lower at 5 days vs. beyond 16 days. Although there was an increase in tidal volume at all ages, frequency decreased significantly from baseline at 5 days, whereas it increased significantly at 16-17, 22-23, and 41-42 days. The decrease in frequency at 5 days of age was mainly due to a significant prolongation in expiratory duration (T E ). In the ventilated group, hypercapnia also caused prolongation in T E at 4-6 days but not at 37-39 days of age. Intravenous administration of bicuculline (GABA A -receptor blocker) abolished the prolongation of T E in response to hypercapnia in the newborn rats. We conclude that newborn rat pups exhibit a characteristic ventilatory response to CO 2 expressed as a centrally mediated prolongation of T E that appears to be mediated by GABAergic mechanisms. carbon dioxide response; infant; premature; chemosensitivity; development; -aminobutyric acid; control of breathing