Cardiovascular adaptations to moderate anemia maintain cerebral perfusion but are inadequate to prevent renal and splanchnic tissue hypoxia

Abstract

Mild to moderate anemia is associated with increased organ 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, with luciferase fused to hypoxia inducible factor (HIF ODD‐Luciferase) was utilized to assess the impact of acute antibody‐mediated anemia on adaptive cardiovascular responses, tissue PO2 (PtO2), and HIF expression. A red blood cell (RBC)‐specific antibody (TER119) induced anemia, reducing hemoglobin concentrations from 144±9 to 94±11 g/L (p<0.006) via intravascular hemolysis and RBC sequestration in the spleen and liver. Anemia‐induced cardiovascular adaptations included: 1) increased peripheral arterial oxygen saturation (p=0.018); 2) increased cardiac output (26%, p=0.011); 3) increased internal carotid blood flow (80%, p<0.001); and 4) augmented cerebrovascular reactivity relative to control mice (p<0.001). All of these mechanisms contributed to the maintenance of brain PtO2 (Control vs. Anemia: 23±10 vs.23±5 mmHg O2, p=0.935). By contrast, no increase in renal blood flow occurred (p=0.239), and kidney PtO2 decreased in anemic mice (21±4 vs. 13±4 mmHg O2, p<0.001). Molecular adaptations to tissue hypoxia included increased HIF‐1α expression within the dorsal renal and hepatic region (30%, p=0.006), and ventral gut region (72%, p=0.017). These findings demonstrate anemia‐induced tissue hypoxia is heterogeneous and organ‐specific and support the hypothesis that renal and splanchnic hypoxia may contribute to increased organ injury and mortality in anemic perioperative patients.Support or Funding InformationThe project described was supported by the St. Michael's Hospital AHSC AFP Innovation Fund Grant Support