ABSTRACT
Toxicities of hemoglobin (Hb) solutions, described in numerous animal resuscitation models, have prominently included fever, hypertension, thrombocytopenia, activation of the complement and coagulation cascades, disseminated intravascular coagulation with parenchymal organ damage, vasculitis with resultant hemorrhagic lesions, reduced tolerance to sepsis, susceptibility to bacterial infections, reticuloendothelial cell blockade, and lethal toxicity. It was recently demonstrated that injection of non-lethal doses of gram-negative bacteria into mice produced 50% and 100% mortality when the animals had been preinfused with either native or cross-linked preparations of cell-free Hb, respectively. The effect of Hb on the biological activity of lipopolysaccharide (LPS) was initially investigated using Limulus amebocyte lysate, the most sensitive in vitro assay for LPS.
