Decompensation characterized by decreased perfusion of the heart and brain during hemorrhagic shock: Role of endothelin-1

Document Type


Publication Date



Background: Endothelin-1 (ET-1), a 21-amino-acid peptide produced by vascular endothelium, is a potent vasoconstrictor and a component of local regulation of vascular tone through its effect on underlying vascular smooth muscle. Hemorrhagic shock (HS) is characterized by compensatory regional vasoconstriction to decrease peripheral tissue perfusion and to maintain core organ perfusion. Decompensation occurs with prolonged duration of HS. In the present study, we hypothesized that systemic and vital organ tissue ET-1 concentrations would correlate with changes in systemic and vital organ perfusion associated with compensatory and decompensatory states of HS. Methods: After surgical instrumentation, HS was induced in male Sprague-Dawley rats by withdrawing blood via femoral artery to a mean arterial pressure of 35 to 40 mm Hg that was maintained for either 30 minutes or 90 minutes in separate groups of male Sprague-Dawley rats. Systemic hemodynamics and regional blood flow were measured using a radioactive microsphere technique. In separate groups of animals, sham, 30 minutes of HS, or 90 minutes of HS, plasma and tissue concentrations of ET-1 were determined using a radioimmunoassay technique. Results: HS maintained for 90 minutes was associated with increased arterial base deficit from 3.6 ± 0.53 mEq/L to 13 ± 0.37 mEq/L, decreased cardiac output from 79 ± 18 mL/min to 18 ± 5 mL/min, and increased systemic vascular resistance from 1,004 ± 102 mm Hg/L·min to 2,392 ± 447 mm · Hg/L min as compared with baseline values. With 90 minutes of HS as compared with 30 minutes of HS, perfusion was significantly decreased in brain (72 ± 11 vs. 29 ± 6 mL/min · 100 g tissue) and heart (483 ± 30 vs. 173 ± 38 mL/min · 100 g tissue) and kidney perfusion was decreased (from 114 ± 28 mL/min/100 g tissue to 29 ± 2 mL/min · 100 g tissue), and ET-1 concentration was increased significantly in brain (cerebral cortex, 89 ± 14 pg/100 g tissue to 144 ± 19 pg/100 g tissue; midbrain, 172 ± 15 pg/100 g tissue to 211 ± 10 pg/100 g tissue), heart (left ventricle, 312 ± 11 pg/100 g tissue to 360 ± 14 pg/100 g tissue), kidney (medulla, 857 ± 61 pg/100 g tissue to 1,277 ± 41 pg/100 g tissue), and plasma (5.31 ± 0.6 pg/100 g tissue to 21.26 ± 2.9 pg/mL). Conclusion. Decreased vital organ and peripheral tissue perfusion, a primary decompensation effect of HS, was apparent with 90 minutes of HS but not with 30 minutes, and was associated with increased vital organ tissue and plasma ET-1 concentrations. These data suggest a role for ET-1 in control mechanisms of progressive vasoconstriction that occurs with prolonged duration of HS.

Publication Title

Journal of Trauma - Injury, Infection and Critical Care



First Page


Last Page



This article was published in Journal of Trauma - Injury, Infection and Critical Care, Volume 53, Issue 3, Pages 531-536.

The published version is available at http://ovidsp.tx.ovid.com/sp-3.15.1b/ovidweb.cgi?&S=KFCAFPLKKLDDFLBINCKKGBIBNKHOAA00&Link+Set=S.sh. .

Copyright © 2002 Wolters Kluwer.

This document is currently not available here.