Rat as a model for humanlike ventilatory adaptation to chronic hypoxia

Abstract

Oxygen uptake (VO2), expired volume (VE), and arterial blood gases were studied in awake, unrestrained rats over 14 days of hypobaric hypoxia (4,300 m altitude) and upon return to acute normoxia. Control data (at 250 m) showed (mean +/- 95% confidence limits (CL)) arterial oxygen pressure (Pao2) = 85.5 +/- 1.1; arterial carbon dioxide pressure (PaCO2) = 39.8 +/- 0.5; arterial pH pHa) = 7.430 +/- 0.009; VE = 78 +/- 3; VO2 = 2.36 +/- 0.09 ml.min-1.100 g-1; and dead space volumetidal volume ratio (VD/VT) = 0.37 +/- 0.04. During 14 days at 4.300 m the rat showed: a) a constant PaO2 (50–52 Torr); b) a time-dependent hyperventilation (e.g., PaCO2 = 30.2 +/- 1.1 at 1 h of hypoxia, 24.7 +/- 1.3 at day and 21.9 +/- 1.0 at 14 days); c) an increase in VE (85% of control) due to both frequency (33%) and VT (40%); d) a continued but reduced hyperventilation upon acute return to normoxia after 5 h to 14 days at 4,300 m; e) a 24% fall in VO2 after 1 h of hypoxia which returned to control by 4 days at 4,300 m; and f) a rise in pHa to 7.52 after 5 h of hypoxia, which fell to 7.45 by 14-day hypoxia. The rat's marked ventilatory response and changing VO2 during acute hypoxia clearly differs from the human response to sojourn at 4,300 m. However, the progressive and sustained hypocapnia during hypoxic exposure and the continued hyperventilation with acute normoxia in the rat provided essential, perhaps unique characteristics for an animal model of human ventilatory acclimatization.