Impaired acclimatization to chronic hypoxia in adult male and female rats following neonatal hypoxia

Abstract

Lumbroso D, Joseph V. Impaired acclimatization to chronic hypoxia in adult male and female rats following neonatal hypoxia. Am J Physiol Regul Integr Comp Physiol 297: R421-R427, 2009. First published June 3, 2009 doi:10.1152/ajpregu.00068.2009.-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 the day before birth to postnatal day 10. The animals were then raised in normal conditions until reaching 12 wk 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 wk 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, V E/V CO2) 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 and 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.hypoxic ventilatory acclimatization; neonatal hypoxia; chronic mountain sickness

Divergent physiological responses in laboratory rats and mice raised at high altitude

“…Rectal temperature was measured immediately at the end of the last hypoxic exposure. V T was calculated from the integrated flow trace as previously described (Lumbroso and Joseph, 2009;Lumbroso et al, 2012), by using standard equations (Bartlett and Tenney, 1970). All values were obtained while the animal had a stable breathing pattern during baseline recordings and within the last 3 min of each condition.…”

Life-long consequences of postnatal normoxia exposure in rats raised at high altitude

“…This postnatal period corresponds to functional development of the respiratory control system and lungs (11,37) and also includes the critical time window during which hypoxic exposure induces longlasting effects on these systems (3,31,39,50). After this period of postnatal exposure, rats were returned to standard conditions.…”

“…It is well documented that postnatal hypoxia blunts growth (16) and induces several alterations of the respiratory system in adults. In rats and mice, postnatal hypoxia results in a lung tissue with fewer but larger alveoli, reduced surface-exchange area, limitations of respiratory gas exchange, and signs of pulmonary hypertension (6,31,50). Similarly, adequate development of the respiratory control system is also dependent on postnatal oxygen level.…”

“…Exposure to hypoxia during early life delays the postnatal maturation of ventilatory response to hypoxia (17,21), reduces respiratory chemoreflex in adult rats (3,39), and reduces carotid body responses to hypoxia and hypercapnia (25). Typically, the period during which neonatal hypoxia induces such long-term changes includes the first 2 wk of postnatal development (3,31,39,50). These experimental studies linking postnatal hypoxia with blunted chemoreflex responses help to explain results from human studies, showing that minute ventilation (V E), but also hypoxic ventilatory response are decreased in high-altitude residents compared with sea-level natives acclimatized to altitude (13,23,45,46).…”

A Translational Model of Incomplete Catch‐Up Growth: Early‐Life Hypoxia and the Effect of Physical Activity

“…Our results extend those of Keith et al 26. in 2000 (RV hypertrophy and pulmonary hypertension) and Lumbroso and Joseph27 in 2009 (RV hypertrophy) who reported on antenatal hypoxia exposure in the pregnant dam. Collectively, these studies showed that abnormalities persist later in life after this early‐life hypoxia exposure was ended.…”