Physiological and microvascular responses to hemoglobin concentration-targeted hemolytic anemia in rats

Hemolytic anemia (HA) is reduced blood oxygen-carrying capacity resulting from the depletion of red blood cells. Treatment for severe cases involves transfusion to improve oxygen delivery (Do₂), which carries risk. In humans, a total hemoglobin (tHb) concentration of 8 g/dL is severe, and <7 g/dL indicates transfusion. Some evidence suggests that compensatory mechanisms maintaining Do₂ are not compromised until <5 g/dL rendering transfusion at 7 g/dL premature. A Sprague-Dawley rat model of phenylhydrazine-induced HA was assessed over decreasing tHb for a Do₂ decompensation point. Three groups (100, 50, or 25% tHb, equating to 16.4, 7.4, or 3.2 g/dL) were generated. Cardiopulmonary, blood chemistry, and oxygenation parameters were measured under anesthesia. Vasoconstrictive responsiveness to phenylephrine was assessed in the exteriorized spinotrapezius. For 50% tHb, cardiopulmonary parameters, Do₂, and lactate levels were similar to those for 100% tHb. Enhanced vasoconstriction occurred with 50% tHb (P < 0.0001), not 25% tHb. The 25% group showed decreases in cardiopulmonary parameters, Do₂, and lactate levels compared with the 100% and 50% groups (P < 0.05). Do₂ showed a positive correlation with lactate levels at 25% tHb, but decompensation, defined by peripheral hypoxia, was not reached. This is the first study relating Do₂ to tHb in rats. A 50% reduction in tHb was supported by vascular compensation, whereas 25% tHb levied the cardiopulmonary system. A decompensation point was not identified. A rising need for treatment as tHb levels decline below 8 g/dL is evident, but, as compensatory mechanisms remain intact as tHb approaches 3.2 g/dL in rats, a transfusion limit of 5 g/dL in healthy patients is supported.NEW & NOTEWORTHY Early, chronic compensation to severe hemolytic anemia is vascular, switching to cardiopulmonary support as hemoglobin levels decline. Oxygen delivery does not correlate with serum lactate level until total hemoglobin is reduced by 75%.