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J Appl Physiol 87: 484-490, 1999;
8750-7587/99 $5.00
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Vol. 87, Issue 2, 484-490, August 1999

Changes in respiratory timing induced by hypercapnia in maturing rats

Jalal M. Abu-Shaweesh1, Ismail A. Dreshaj1, Agnes J. Thomas2, Musa A. Haxhiu1,2,3, Kingman P. Strohl2,3, and Richard J. Martin1

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 gamma -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 (TE). In the ventilated group, hypercapnia also caused prolongation in TE at 4-6 days but not at 37-39 days of age. Intravenous administration of bicuculline (GABAA-receptor blocker) abolished the prolongation of TE in response to hypercapnia in the newborn rats. We conclude that newborn rat pups exhibit a characteristic ventilatory response to CO2 expressed as a centrally mediated prolongation of TE that appears to be mediated by GABAergic mechanisms.

carbon dioxide response; infant; premature; chemosensitivity; development; gamma -aminobutyric acid; control of breathing


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