Assessment of Cardiovascular Adaptation, Organ Perfusion, and Tissue Hypoxia in an Antibody Mediated Model of Moderate Anemia

Anemia is associated with increased brain and kidney injury, and mortality in surgical patients by undefined mechanisms. We hypothesize that anemia-induced tissue hypoxia is a potential unifying mechanism. A transgenic mouse model(HIF-ODD Luciferase) was utilized to assess the impact of antibody-mediated anemia on adaptive cardiovascular responses, tissue PO2(PtO2), and hypoxia-inducible factor(HIF)-expression. Red blood cell(RBC)-specific antibody(TER119) induced anemia via intravascular hemolysis, and splenic and hepatic RBC sequestration. Anemia-induced cardiovascular adaptations included increased: 1)peripheral arterial oxygen saturation, 2)cardiac output, 3)internal carotid blood flow, and 4)cerebrovascular reactivity. These mechanisms contributed to maintain brain PtO2. By contrast, renal perfusion was not increased, leading to a reduced renal PtO2. Also, increased HIF-1Îą expression was observed in renal, hepatic, and gut regions. These findings demonstrate that anemia-induced tissue hypoxia occurs in an organ specific manner. These data support the hypothesis that renal and splanchnic hypoxia may contribute to increased organ injury and mortality in anemic patients.M.Sc