Long-term respiratory effects of neonatal hypoxia in the rat

Rats maintained in a hypoxic environment during the 1st wk after birth decrease body growth and O2 consumption (VO2) and increase minute ventilation (VE). At the same time the lungs undergo changes in structure, which suggests a protection of the gas exchange area (Mortola et al. J. Appl. Physiol. 61: 1329-1336, 1986). In this study we asked to what extent these adaptive changes would persist after return to normoxia. Newborn rats were kept in 10% O2 during the 1st wk of life, then returned to normoxic breathing, and measurements were performed weekly. Body weight (BW) increased very little during the week of hypoxia, but after return to normoxia body growth was more than in control rats, and eventually BW reached the control value at 2 mo of age. Both VO2/BW (measured manometrically) and VE/BW (measured by flow plethysmography or by the barometric method) were above control in the 1st wk after hypoxia, probably reflecting the higher O2 demands of the rapidly growing animals. However, VE remained elevated even at 7-8 wk of age (i.e., postpuberty), at a time when both BW and VO2 were as in controls. Measurements of blood gases at this age indicated that the persistent hyperventilation was not due to hypoxemia and was accompanied by hypocapnia and alkalosis. Hematocrit and heart mass-to-BW ratio, elevated in hypoxia, returned to control values within 1 wk, whereas dry lung weight-to-BW ratio remained above the control values as much as during the hypoxic exposure. These results suggest that early postnatal hypoxia in the rat could have long-term effects on the regulation of breathing.