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Accession Number:
ADA289558
Title:
Mechanisms of Hypertension After Cross-Linked Hemoglobin Blood-Substitute Transfusion.
Descriptive Note:
Midterm rept.,
Corporate Author:
MAYO FOUNDATION ROCHESTER MN
Report Date:
1994-12-01
Pagination or Media Count:
19.0
Abstract:
The USAMRDC has developed a blood substitute containing cross-linked human hemoglobin XL-Hgb in a physiologic saline solution. In animal models, this material can sustain life in the absence of red blood cells and is effective in resuscitating experimental animals from hypovolemic hemorrhagic shock. A persistent side-effect of XL-Hgb administration in animals has been marked arterial and pulmonary hypertension. The mechanism of this hypertension is unknown, but it is hypothesized that the XL-Hgb scavenges the endogenous vasodilating substance nitric oxide NO. In experiements to date, our group has demonstrated that XL-Hgb administration 1 appears to blunt NO-mediated vasodilation in isolated blood vessels 2 disrupts the normal metalbolism of catecholamines from the adrenal medulla and sympathetic nerve endings 3 blunts NO-mediated vasodilation in vivo 4 casues acute volume expansion and hypertension without the normally observed diuresis and natriuresis in vivo. Studies to date generally confirm the hypothesis that XL-Hgb interferes with NO function in isolated tissues and whole animals. Additionally, other poorly understook physiologic mechanisms may also contribute to the hypertension. Studies planned in the second half of this contract will continue to explore NO-mediated and other mechanisms which underlie the hypertension seen after XL-Hgb transfusion.
Distribution Statement:
APPROVED FOR PUBLIC RELEASE
