RESUSCITATION AFTER HEMORRHAGE USING RECOMBINANT HUMAN HEMOGLOBIN (RHB1.1) IN RATS - EFFECTS ON NITRIC-OXIDE AND PROSTANOID SYSTEMS

Objectives: Hemoglobin based oxygen carriers are designed to replace b lood volume and to increase oxygen delivery to tissues after blood los s. The goals of the present study were two fold: a) to determine the s ystemic and regional vascular effects of resuscitation with recombinan t human hemoglobin (rHb1.1) in rats during controlled hemorrhage; and b) to determine whether nitric oxide (NO) or prostaglandins were invol ved in the observed responses. Design: Paralyzed, ventilated rats were hemorrhaged (18 mL blood/kg body weight) during halothane anesthesia and allowed to stabilize for 30 mins. Systemic and regional hemodynami cs and oxygen delivery were monitored at three time points, using the radioactive microsphere method. Microspheres were first infused at the end of the hemorrhage stabilization period (t = 0 min), rHb1.1 (1 g/k g body weight) or rHb1.1 diluent (phosphate buffered saline, 36 mL/kg body weight) were infused over 20 mins and microspheres were administe red again, 30 mins later (t = 50 mins). Saline (0.5 mL), indomethacin (5 mg/kg to inhibit cyclooxygenase), or N-G-monomethyl-L-arginine (L-N MMA, 100 mg/kg, to inhibit NO synthase) were then infused in rHb1.1-tr eated rats and microspheres injected once more (t = 80 mins). Setting: Research laboratory. Subjects: Male Wistar rats (n = 37). interventio ns: Recombinant human hemoglobin (rHb1.1), rHb1.1 diluent (phosphate b uffered saline) resuscitation of hemorrhaged rats. Saline, L-NMMA, or indomethacin treatment after resuscitation. Measurements and Main Resu lts: Resuscitation with rHb1.1 increased mean arterial pressure (MAP), cardiac output, and systemic oxygen delivery significantly when compa red with diluent. After rHb1.1 resuscitation, regional blood flows wer e significantly increased in skin, kidney, spleen, and heart compared with diluent resuscitation. Compared with saline treatment after rHb1. 1 resucitation, L-NMMA increased MAP and regional resistances in virtu ally ail tissues; indomethacin did not alter MAP, but increased resist ance in the brain. Conclusions: These data indicate that rHb1.1 resusc itation was more effective than diluent in improving systemic and regi onal hemodynamics and oxygen delivery, suggesting that rHb1.1 may be o f benefit in the treatment of acute blood loss. Increased resistance a fter L-NMMA in the presence of rHb1.1 indicated that rHb1.1 resuscitat ion did not eliminate NO dependent circulatory control. Increased resi stance after indomethacin in brain indicated that vasodilator prostano ids were important in regulating vascular resistance in these tissues after rHb1.1 resuscitation.