PULMONARY VASCULAR ADAPTATIONS TO AUGMENTED POLYCYTHEMIA DURING CHRONIC HYPOXIA

We previously found that augmentation of polycythemia by exogenous hum an recombinant erythropoietin (EPO) failed to worsen the severity of h ypoxic pulmonary hypertension in rats. We asked whether this unexpecte d finding was related to reductions in cardiac output, left ventricula r end-diastolic pressure, pulmonary vascular resistance, or some combi nation of these factors. Four groups of Sprague-Dawley rats were studi ed over a 3-wk period: hypoxic (0.5 ATM) and normoxic animals each inj ected with EPO (500 U/kg sc thrice weekly) or saline (control animals) . As observed previously, we found that pulmonary arterial (PA) pressu res and right ventricular hypertrophy were not increased in EPO-treate d rats despite significant increases in hematocrit and blood viscosity . Cardiac outputs, blood volumes, and left ventricular end-diastolic p ressures were similar in EPO-treated and control rats. Acute PA pressu re responses to acute normoxia in hypoxic rats and to acute hypoxia in normoxic rats were similar, suggesting no differences in vasoreactivi ty. However, lungs isolated from EPO-treated hypoxic rats had lower pu lmonary vascular resistance than saline-treated hypoxic rats when perf used with blood from normocythemic donor rats. PA medial thickness and the percentage of muscularized small PAs were significantly lower in EPO-treated hypoxic rats. These results indicate that augmented polycy themia fails to worsen hypoxic pulmonary hypertension in rats because of a decrease in the severity of structural remodeling.