Tolerance of anemia: understanding the adaptive physiological mechanisms which promote survival.

Acute anemia and hemodilution are associated with increased organ injury (brain, kidney) and mortality in patients undergoing surgery. A more complete understanding of the adaptive physiological mechanisms which maintain tissue oxygen delivery, and the hemoglobin concentration at which these mechanisms are overwhelmed, would help to direct treatments to improve event free survival in patients who experience acute anemia. Adaptive cardiovascular and cellular responses are key to maintaining survival during acute anemia. We have identified neuronal nitric oxide synthase (nNOS) and hypoxia inducible factor (HIF) promote survival during acute anemia in animal models. In addition, activation of tissue nNOS may promote oxidation of hemoglobin to methemoglobin: a potential biomarker of anemia-induced tissue hypoxia. We continue to explore the possibility that methemoglobin, and other hypoxic signaling molecules, may be biomarkers of anemia induced tissue hypoxia which can be used to guide optimal treatment of anemic patents.