Physiologic responses of cross-linked hemoglobin in endotoxin-treated rats.

Purified human cross-linked hemoglobin (ααHb) as well as recombinant human hemoglobin is undergoing clinical trials in the setting of acute blood loss and perioperative hemodilution. We have previously demonstrated that in rabbits with circulating plasma Hb, such as ααHb, infusion of endotoxin (LPS) impairs myocardial contractility which results in hypotension, tissue hypoperfusion and increased mortality. The untoward cardiovascular effects occurring after the combined infusion of LPS and ααHb in this model are similar to those reported for other agents that inhibit nitric oxide (NO) availability. To determine if the deleterious effects of ααHb and LPS were species specific, we performed similar studies in rats. Anesthetized Sprague-Dawley rats received LPS (4 mg/kg or 40 mg/kg) alone or in combination with ααHb (0.7 g/kg). Mean arterial blood pressures (MAP) increased in the group that received ααHb alone (105±8 to 120±7 mm Hg, p=0.2) and a decrease was noted in the groups that received low dose LPS (4 ...