Impact of increased hematocrit on right ventricular afterload in response to chronic hypoxia.

Abstract

Chronic hypoxia causes chronic mountain sickness through hypoxia-induced pulmonary hypertension (HPH) and increased hematocrit. Here, we investigated the impact of increased hematocrit and HPH on right ventricular (RV) afterload via pulmonary vascular impedance. Mice were exposed to chronic normobaric hypoxia (10% oxygen) for 10 (10H) or 21 days (21H). After baseline hemodynamic measurements, ∼500 μl of blood were extracted and replaced with an equal volume of hydroxyethylstarch to normalize hematocrit and all hemodynamic measurements were repeated. In addition, ∼500 μl of blood were extracted and replaced in control mice with an equal volume of 90% hematocrit blood. Chronic hypoxia increased input resistance (Z0 increased 82% in 10H and 138% in 21H vs. CTL; P < 0.05) and characteristic impedance (ZC increased 76% in 10H and 109% in 21H vs. CTL; P < 0.05). Hematocrit normalization did not decrease mean pulmonary artery pressure but did increase cardiac output such that both Z0 and ZC decreased toward control levels. Increased hematocrit in control mice did not increase pressure but did decrease cardiac output such that Z0 increased. The paradoxical decrease in ZC with an acute drop in hematocrit and no change in pressure are likely due to inertial effects secondary to the increase in cardiac output. A novel finding of this study is that an increase in hematocrit affects the pulsatile RV afterload in addition to the steady RV afterload (Z0). Furthermore, our results highlight that the conventional interpretation of ZC as a measure of proximal artery stiffness is not valid in all physiological and pathological states.