Submitted on January 30, 2009
Revised on June 2, 2009
Accepted on June 2, 2009
Impaired acclimatization to chronic hypoxia in adult male and female rats following neonatal hypoxia
Delphine Lumbroso and Vincent Joseph1*
1 Centre de recherche CHUQ
* To whom correspondence should be addressed. E-mail: joseph.vincent{at}crsfa.ulaval.ca.
We tested the hypothesis that neonatal exposure to hypoxia alters acclimatization to chronic hypoxia later in life. Rat pups were exposed to normobaric hypoxia (12% O2 - nHx group) in a sealed chamber, or to normoxia (21% O2 - nNx group) from prenatal day 1 to postnatal day 10. The animals were then raised in normal conditions until reaching 12 weeks of age. At this age, we assessed ventilatory and hematological acclimatization to chronic hypoxia by exposing male and female nHx and nNx rats for 2 weeks to 10% O2. Minute ventilation, metabolic rate, hypoxic ventilatory response, hematocrit and hemoglobin levels were measured both before and after acclimatization. We also quantified right ventricular hypertrophy as an index of pulmonary hypertension both before and after acclimatization. There was a significant effect of neonatal hypoxia that decreases ventilatory response (relative to metabolic rate, VE/VCO2 ) to acute hypoxia before acclimatization in males but not in females. nHx rats had an impaired acclimatization to chronic hypoxia characterized by altered respiratory pattern, elevated hematocrit and hemoglobin levels after acclimatization, in both males and females. Right ventricular hypertrophy was present before and after acclimatization in nHx rats indicating that neonatal hypoxia results in pulmonary hypertension in adults. We conclude that neonatal hypoxia impairs acclimatization to chronic hypoxia in adults, and may be a factor contributing to the establishment of chronic mountain sickness in humans living at high altitude.
