Changes in respiratory timing induced by hypercapnia in maturing rats.
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 (GABA(A)-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 CO(2) expressed as a centrally mediated prolongation of TE that appears to be mediated by GABAergic mechanisms.
Abu-Shaweesh
J M
JM
Department of Pediatrics, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA.
Dreshaj
I A
IA
Thomas
A J
AJ
Haxhiu
M A
MA
Strohl
K P
KP
Martin
R J
RJ
D000367:Age Factors; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D002245:Carbon Dioxide / Q000494:pharmacology*; D003655:Decerebrate State; D018756:GABA Antagonists / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists; D006935:Hypercapnia / Q000503:physiopathology*; D010791:Phrenic Nerve / Q000378:metabolism; D010991:Plethysmography; D051381:Rats; D017207:Rats, Sprague-Dawley; D012119:Respiration; D012121:Respiration, Artificial; D013990:Tidal Volume; D014628:Vagotomy; D012122:Ventilators, Mechanical
D018756:GABA Antagonists; D058787:GABA-A Receptor Antagonists; D002245:Carbon Dioxide; D001640:Bicuculline