O-Raffinose Crosslinking Substantially Ameliorates the Vasoconstrictive and Nitric-Oxide-Inactivating Effects of Unmodified Human Hemoglobin in the Rat

摘要

We studied the hemodynamic effects of a 20% exchange transfusion with whole blood or highly purified human hemoglobin Ao. We compared the effects of unmodified hemoglobin with o-raffinose crosslinked oligomers of hemoglobin (modified hemoglobin). The unmodified SFH increased systemic vascular resistance (SVR) by approx. 40%, and renal vascular resistance (RVR) by approx. 25%. Cardiac output was markedly reduced (by approx. 20%) and mean arterial pressure (MAP) only modestly increased (by approx. 13%). In contrast, the modified hemoglobin solution caused less increase in SVR (approx. 14%) and did not alter renal hemodynamics or blood pressure. We also compared the ability of the unmodified and crosslinked hemoglobins to inactivate nitric oxide (NO) in vitro using three separate assays; platelet NO release, NO-stimulated platelet cGMP production and EDRF-mediated inhibition of platelet aggregation. The unmodified hemoglobin inactivated NO to a markedly greater extent than the o-raffinose crosslinked hemoglobin in all three assays. Thus, chemical crosslinking with o- raffinose reduces the systemic and renal vasoconstriction as well as the NO- inactivating effects of hemoglobin. We suggest that the change in the vasoactive effects of unmodified hemoglobin induced by o-raffinose crosslinking is related to the associated reduction in NO-inactivation.