Three general mechanisms have been proposed to explain rapid increases in red blood cell concentration in vertebrates in response to hypoxia: spleen emptying, red blood cell swelling, and decreases in plasma volume. We have experimentally tested these potential mechanisms for the hemoconcentration of red blood cells associated with hypoxemia in cold (10 degrees C), submerged bullfrogs. The mean increase of hematocrit was approximately 1.4-fold (the increase was highly variable between individual frogs) when arterial oxygen saturation was reduced from 80% to 8% by lowering ambient O2 partial pressure (PO2). The largest response was seen when arterial oxygen saturation was below 33% (a saturation that is not unusual in submerged amphibians). There was no difference between hematocrit increases during hypoxemia in spleen-ligated compared with sham-operated frogs submerged in hyperoxic, normoxic, and hypoxic water, suggesting that spleen emptying is not the primary mechanism. Increased hematocrit was not due to red blood cell swelling: mean corpuscular hemoglobin concentration increased slightly as hematocrit increased, indicating that red blood cells shrank slightly rather than swelling. Plasma volume, measured in a separate group of animals by dilution of 51Cr-labeled autologous red blood cells, decreased almost 50% during hypoxemia, closely correlated with a mean increase of 1.76-fold of hematocrit. We thus conclude that the hematocrit increase seen during hypoxemia in bullfrogs is caused by a loss of plasma volume. This has important implications for cardiovascular function, since blood viscosity, oxygen carrying capacity, and cardiac output are all affected by changes in plasma volume.
