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Changes in respiratory timing induced by hypercapnia in maturing rats
J M Abu-Shaweesh1, I A Dreshaj, A J Thomas
1Department of Pediatrics, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA.
Journal of Applied Physiology (Bethesda, Md. : 1985)
|August 13, 1999
Summary
Newborn rats show a unique breathing response to high carbon dioxide levels, involving a longer exhalation phase. This response, mediated by GABAergic pathways, changes as the rats mature.
Area of Science:
- Physiology
- Neuroscience
- Developmental Biology
Background:
- Premature infants exhibit an impaired ventilatory response to hypercapnia, characterized by decreased respiratory frequency.
- This attenuated response is hypothesized to be of central origin and involve gamma-aminobutyric acid-ergic (GABAergic) pathways.
Purpose of the Study:
- To investigate the central mechanisms underlying the hypercapnic ventilatory response in developing Sprague-Dawley rats.
- To determine the role of GABAergic pathways in mediating the respiratory response to hypercapnia in newborn rats.
Main Methods:
- Utilized whole-body plethysmography in unrestrained rats across four postnatal ages (5, 16-17, 22-23, 41-42 days).
- Measured phrenic nerve responses to hypercapnia in ventilated, decerebrate, vagotomized, paralyzed rats at two age groups (4-6 and 37-39 days).
- Administered bicuculline (a GABA(A)-receptor blocker) intravenously to assess its effect on respiratory response.
Main Results:
- Hypercapnia induced a significantly lower minute ventilation increase in 5-day-old rats compared to older rats.
- In young rats, hypercapnia prolonged expiratory duration (TE) and decreased respiratory frequency, while older rats showed increased frequency.
- Bicuculline administration abolished the hypercapnia-induced TE prolongation in newborn rats.
Conclusions:
- Newborn rat pups display a distinct ventilatory response to CO(2), involving a centrally mediated prolongation of TE.
- This response is mediated by GABAergic mechanisms, highlighting their crucial role in neonatal respiratory control.
- The findings suggest that developmental changes in GABAergic signaling influence the maturation of the hypercapnic ventilatory response.