HEMODYNAMIC AND RENAL EFFECTS OF CROSS-LINKED HEMOGLOBIN INFUSION

It is well known that hemoglobin binds nitric oxide (NO) and produces a pronounced vasoconstriction in isolated arteries. However, it is deb atable whether such an effect takes place in whole animals, because he moglobin also catalyzes the formation of prostaglandins from arachidon ic acid. Short-term studies were performed to evaluate the effects ind uced by intravenous infusion of cross-linked hemoglobin (XL-Hb) on blo od pressure (BP) and renal, iliac, and mesenteric flows, and on renal function in six anesthetized dogs. A similar volume-matched expansion with 6% dextran was used as a control (n = 6). Glomerular filtration r ate (GFR), urinary flow, and total and fractional sodium excretion wer e measured before and after XL-Hb or dextran infusion to evaluate poss ible renal function changes. XL-Hb administration resulted in a 29% el evation in BP and a significant decrease of blood flow (30-37%) to the three vascular beds. XL-Hb did not alter GFR or sodium excretion, des pite the increase in BP. In contrast, the administration of dextran di d not significantly alter BP but induced a significant increase (6-13% ) of blood flow in the three vascular beds. These changes were accompa nied by threefold increases in urinary flow and sodium excretion witho ut alterations in GFR. The binding effect of XL-Hb on NO was studied i n isolated renal arteries in organ chambers. These in vitro studies sh owed that XL-Hb blunted the endothelium-mediated vasodilator response to calcium ionophore A-23187 and to acetylcholine. Our results demonst rate that XL-Hb administration is followed by hypertension, vasoconstr iction, and blunted natriuresis. All these effects are compatible with the scavenging effect on NO attributed to XL-Hb.