Pathophysiological effects of hemodilution in chronic mountain sickness in rats

We examined the effect of isovolemic hemodilution in a rat model of chronic mountain sickness (CMS). After 30 days at simulated high altitude (5,500 m), Hilltop rats had developed evidence of CMS: severe hypoxemia, polycythemia, and pulmonary arterial hypertension. Isovolemic hemodilution to a mean hematocrit of 46 +/- 5% was well tolerated by both the hypoxia-sensitive Hilltop rats and the companion Madison rat strain that does not develop CMS. After hemodilution, we found no evidence of sustained improvements in ventilation or gas exchange in either strain. Despite the fall in blood viscosity, cardiac output increased only marginally, and pulmonary arterial hypertension persisted in the Hilltop rats. Vascular hindrance increased after hemodilution, preventing a significant decline in pulmonary and systemic vascular resistances in the Hilltop rats. Blood O2 content and the coefficient of O2 delivery fell after hemodilution, but O2 consumption was sustained at a normal level after hemodilution by increasing the extraction fraction in the Hilltop strain. There was systemic hypotension through the first day of hemodilution, but this was the only apparent adverse effect of hemodilution. We conclude that isovolemic hemodilution was well tolerated despite the reduction in tissue O2 delivery. However, hemodilution failed to improve any of the respiratory and cardiovascular manifestations of CMS in Hilltop rats.