Diaspirin crosslinked hemoglobin improves systemic oxygen uptake in oxygen supply-dependent septic rats

Abstract

Diaspirin crosslinked hemoglobin (DCLHb) is a cell-free hemoglobin derived from human erythrocytes. DCLHb has been shown to improve blood flow to vital organs in healthy and septic animals. In this study, we determined the efficacy of DCLHb by comparing its effect on systemic O2 uptake to freshly stored and aged red blood cells (RBCs) in septic rats. Twenty-four hours after induction of sepsis by cecal ligation and perforation, O2 supply dependency was created by isovolemic hemodilution with rat plasma. In O2 supply dependency, rats were randomized to receive an exchange transfusion of 7.5 ml "fresh" RBCs (stored < 6 d; Hct: 70%), "fresh" diluted RBCs (stored < 6 d; Hct: 30%), "old" RBCs (stored 28 to 35 d; Hct: 70%), or DCLHb (Hb: 100 g/L). We found, that survival following O2 supply dependency and transfusion with old RBCs was poor (33% versus 91.7% in the other groups; p < 0.01), precluding further analysis of post-transfusion data from this group. Systemic O2 uptake increased in all remaining groups (p < 0.001), while systemic O2 delivery increased with "fresh" RBCs (p < 0.0001) and "fresh" diluted RBCs (p < 0.05) but not with DCLHb. Systemic O2 extraction increased with DCLHb as compared to baseline (p < 0.05) and to the other groups (p < 0.0001). Improved tissue oxygenation was associated with an increase in blood pressure and a fall in arterial lactate in all groups. We conclude that transfusion of DCLHb or "fresh" RBCs was efficacious at increasing systemic O2 uptake in O2 supply-dependent, septic rats.