CARDIOVASCULAR TOXICITY OF HUMAN CROSS-LINKED HEMOGLOBIN IN A RABBIT ENDOTOXEMIA MODEL

Objective: To determine the possible adverse effects of human cross-li nked hemoglobin in endotoxemia. Design: Prospective, controlled, labor atory trial. Setting: Animal research laboratory. Subjects: New Zealan d white rabbits. Interventions: Conscious rabbits received intravenous infusions of either lipopolysaccharide (LPS) alone (10 mu g/kg, Esche richia coil 0111:84), human hemoglobin cross linked between the alpha chains (alpha alpha Hb, 0.7 g/kg), or both LPS and alpha alpha Hb. The cardiovascular effects of alpha alpha Hb and LPS as single agents or administered together were then studied in anesthetized rabbits. Measu rements and Main Results: Mortality in conscious animals that received alpha alpha Hb followed by LPS 4 hrs later (n = 5), or LPS and alpha alpha Hb at the same time (n = 6) was 60% and 67%, respectively. In an esthetized animals, infusion of both LPS and alpha alpha Hb (n = 6) re sulted in hypoxia, lactic acidosis, ventricular arrhythmias, and decre ased myocardial contractility and left ventricular pressure. In contra st, anesthetized rabbits that received alpha alpha Hb (n = 5) or LPS ( n = 5) alone did not develop hypoxia, acidosis, alteration in myocardi al contractility, or arrhythmias. Furthermore, death did not occur in any of the conscious animals that received either LPS (n = 7) or alpha alpha Hb (n = 4) as single agents. Conclusions: In an animal model of nonlethal endotoxemia, infusion of alpha alpha Hb significantly incre ases mortality. Our data suggest that mortality may be due to the acut e increased cardiopul monary toxicity of alpha alpha Hb in animals wit h underlying endotoxemia.