• C Krishnamurti, A J Carter, P Maglasang, J R Hess, M A Cutting, and B M Alving.
• Department of Hematology and Vascular Biology, Walter Reed Army Institute of Research, Washington, DC 20307-5100, USA.
• Crit. Care Med. 1997 Nov 1; 25 (11): 1874-80.

ObjectiveTo determine the possible adverse effects of human cross-linked hemoglobin in endotoxemia.DesignProspective, controlled, laboratory trial.SettingAnimal research laboratory.SubjectsNew Zealand white rabbits.InterventionsConscious rabbits received intravenous infusions of either lipopolysaccharide (LPS) alone (10 micrograms/kg, Escherichia coli 0111:B4), 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.Measurements And Main ResultsMortality 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 anesthetized animals, infusion of both LPS and alpha alpha Hb (n = 6) resulted in hypoxia, lactic acidosis, ventricular arrhythmias, and decreased myocardial contractility and left ventricular pressure. In contrast, anesthetized rabbits that received alpha alpha Hb (n = 5) or LPS (n = 5) alone did not develop hypoxia, acidosis, alteration in myocardial 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.ConclusionsIn an animal model of nonlethal endotoxemia, infusion of alpha alpha Hb significantly increases mortality. Our data suggest that mortality may be due to the acute increased cardiopulmonary toxicity of alpha alpha Hb in animals with underlying endotoxemia.

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