Time course of cardiopulmonary responses to high altitude in susceptible and resistant rat strains.

We have identified two strains (H and M) of Sprague-Dawley rat with distinctly different susceptibilities and cardiopulmonary responses to hypoxia. In this study, we studied the development of cardiopulmonary and hematological responses to hypoxia and the post-hypoxic regression of these responses in the two strains over time. Under sea level conditions, there were no differences between the two strains. On exposure to hypobaric hypoxia (0.5 atm), right ventricular peak systolic pressure (RVPP) and right ventricular hypertrophy (RVH) increased more rapidly in the susceptible (H) than in the resistant (M) strain. In contrast, post-hypoxic reversal of these changes occurred at comparable rates. Hematocrits rose at similar rates in the two strains until after two weeks, when that of the H strain slightly exceeded that of the M strain. With the progression of RVH, left ventricular plus septal to body weight ratio (LV + S) g/100 g bw decreased in M rats but increased in the H rats. As a result, a conspicuous overall cardiac hypertrophy developed in the H rats but only a minimal cardiac hypertrophy occurred in the M strain. The data show that susceptibility to hypoxia in H rats is associated with more rapid development of RV systolic hypertension and biventricular hypertrophy than in M rats. The mechanism for the accelerated cardiopulmonary responses in the H rats most likely involves greater hypoxic pulmonary vasoconstriction or pulmonary vascular remodeling. Differences in hematocrit between the strains do not contribute to the early cardiopulmonary responses.