The Effects of Diaspirin Cross-Linked Hemoglobin on the Tone of Human Saphenous Vein

Abstract

Diaspirin cross-linked hemoglobin (DCL-Hb), when infused into animals, causes vasoconstriction thought to be caused by nitric oxide (NO) binding by the hemoglobin molecule. The purpose of this study was to ascertain whether DCL-Hb causes vasoconstriction in human saphenous vein taken from patients undergoing myocardial revascularization and whether NO scavenging is the mechanism. The direct effect of DCL-Hb on saphenous vein tone was tested by adding increasing concentrations (10−8 to 10−5M) of the drug. In an additional series of experiments, the influence of DCL-Hb on the dilator response to endothelial dependent and independent vasodilators was tested. This was achieved by attempting either to reverse the effects of acetylcholine, sodium nitroprusside, or S-nitrosylglutathione with prior incubation with DCL-Hb or to inhibit the dilator response in vessels preconstricted with 10−6M norepinephrine. There was no effect of DCL-Hb alone on saphenous vein tone. DCL-Hb significantly reduced vasodilatation with all vasodilators (P < 0.05). After maximal relaxation with sodium nitroprusside and s-nitrosylglutathione, there was significant vasoconstriction with DCL-Hb at concentrations larger than 10−6M, (P < 0.05). The authors conclude that DCL-Hb does not constrict human saphenous vein but can affect vessel tone by reversal of the effect of endogenously or exogenously released NO. Implications Hemoglobin solutions are used as alternatives to blood transfusion. In animals, they cause vasoconstriction by binding nitric oxide. This is an in vitro study of the effects of one hemoglobin solution in human blood vessels. It shows that this hemoglobin solution alone had no effect in human tissue but antagonized other agents used to alter vessel tone.