CO2-induced prolongation of expiratory time during early development.
In these studies, we determined the contribution of central mechanisms and the role of GABA(A)-receptor signal transduction pathways in mediating hypercapnia-induced slowing of breathing frequency. Experiments were performed in decerebrate, vagotomized, paralyzed and mechanically ventilated piglets of 3-5 days and 2-3 weeks of age (n=19). Repeated exposure to progressive hyperoxic hypercapnia induced a reproducible increase in phrenic nerve activity, accompanied by a CO2 concentration-dependent increase in expiratory duration. No differences were observed in piglets with intact or cut carotid sinus nerves. Intravenous administration of bicuculline (2 mg/kg: n=7), a gamma-aminobutyric acid (GABA(A)) receptor antagonist, significantly reduced the CO2-induced prolongation of TE. These data demonstrate for the first time that in early postnatal life, hypercapnia induced increase in phrenic activity is associated with centrally mediated prolongation of expiratory duration. Furthermore. the results suggest that brainstem GABAergic mechanisms play an important role in CO2-induced prolongation of expiratory time during early development.
Dreshaj
I A
IA
Department of Pediatrics and Medicine, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.
Haxhiu
M A
MA
Abu-Shaweesh
J
J
Carey
R E
RE
Martin
R J
RJ
D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D002245:Carbon Dioxide / Q000097:blood / Q000494:pharmacology*; D003655:Decerebrate State / Q000503:physiopathology; D005260:Female; D018756:GABA Antagonists / Q000494:pharmacology; D006935:Hypercapnia / Q000503:physiopathology; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects / Q000502:physiology; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology; D010791:Phrenic Nerve / Q000502:physiology; D011149:Pons / Q000187:drug effects / Q000502:physiology; D015656:Respiratory Mechanics / Q000187:drug effects*; D013552:Swine; D014628:Vagotomy
D018756:GABA Antagonists; D002245:Carbon Dioxide; D001640:Bicuculline