Submitted on December 11, 2007
Accepted on February 19, 2008
Chronic intermittent hypoxia reduces ventilatory long-term facilitation and enhances apnea frequency in newborn rats
Cecile Julien1, Aida Bairam1, and Vincent Joseph1*
1 Pediatrie, Universite Laval, Quebec, Canada
* To whom correspondence should be addressed. E-mail: joseph.vincent{at}crsfa.ulaval.ca.
Ventilatory long-term facilitation (LTF, defined as gradual increase of minute ventilation following repeated hypoxic exposures) is well described in adult mammals and is hypothesized to be a protective mechanism against apnea. In newborns, LTF is absent during the first postnatal days, but its precise developmental pattern is unknown. Accordingly, this study describes this pattern of postnatal development. Additionally, we tested the hypothesis that chronic intermittent hypoxia (CIH) from birth alters this development. LTF was estimated in vivo using whole body plethysmography by exposing rat pups (at postnatal days P1, P4 and P10) to 10 brief hypoxic cycles (nadir 5% O2) and respiratory recordings during the following 2 hours (recovery -21%O2). Under these conditions, ventilatory LTF (gradual increase of minute ventilation during recovery) was clearly expressed in P10 rats but not in P1 and P4. In a second series of experiments, rat pups were exposed to CIH during the first 10-postnatal days (6 brief cyclic exposure at 5% O2 every 6 min followed by 1 h under normoxia, 24h/24). Compared to P10 control rats, CIH enhanced hypoxic ventilatory response (estimated during the hypoxic cycles) specifically in male rat pups. Ventilatory LTF was drastically reduced in 10-day old rats exposed to CIH, which was associated to higher apnea frequency during recovery. We conclude that CIH from birth enhances hypoxic chemoreflex and disrupts LTF development thus likely contributing to increase apnea frequency.
