Mechanisms of Hypertension After Cross-Linked Hemoglobin Blood SubstituteTransfusion

摘要

The USAMRDC has developed a 'blood substitute', consisting of a cross-linkedhuman hemoglobin in saline solution. The rationale for developing such a product is that it might be useful in the acute resuscitation of soldiers in the battlefield, and also might have utility as an oxygen-carrying volume expander in situations where administration of blood is logistically difficult. In animal models, this material can sustain life in the absence of red cells. It is also effective in resuscitating experimental animals after acute hemorrhage. A common side effect of XL-Hgb administration in animals has been marked arterial and pulmonary hypertension. while the mechanism of this hypertension is unknown, it is thought that XL-llgb scavenges the endogenous vasodilating substance nitric oxide (NO). In the execution of this contract our group has attempted to determine the effects of this XL-Hgb administration on (1) NO-mediated vasodilation in isolated blood vessels; (2) the metabolism of vasoconstricting catecholamines in the adrenal medulla and sympathetic nerve endings; (3) NO-mediated vasodilation in vivo; and (4) the effects on renal sodium and volume regulation in vivo. The studies conducted as part of this contract generally confirm the hypothesis that XL-Hgb interferes with NO function on isolated tissues in whole animals. It also appears that other vasoconstricting mechanisms might contribute to the hypertension observed during XL-Hgb administration.