Abstract |
Ischemia of a vascular bed followed by reestablishment of blood flow results in an accelerated and severe form of tissue injury known as " reperfusion injury." We have investigated reperfusion injury in cats subjected to either myocardial ischemia-reperfusion or splanchnic ischemia-reperfusion. In both cases, a critical early event after reperfusion is endothelial dysfunction characterized by reduced release of endothelium-derived relaxing factor now known to be nitric oxide (NO). Endothelial dysfunction leads to adherence of polymorphonuclear (PMN) leukocytes to the dysfunctional endothelium. Infusion of a sydnonimine NO donor (C87-3754), but not a similar compound lacking the NO moiety (C88-3934), just before reperfusion protected in both forms of ischemia-reperfusion. In the first case, C87-3754, but not C88-3934, attenuated myocardial necrosis, and in the second case, the NO donor improved survival and moderated the indices of shock. In both cases, C87-3754 preserved the endothelium of the ischemic-reperfused vasculature and exerted anti-PMN effects (i.e., reduced PMN adherence to the endothelium or attenuated PMN release of superoxide radicals). Thus, an NO donor infused at a rate calculated to replace the lost NO from the vascular endothelium of the ischemic region exerts significant protective effects on reperfusion of that ischemic vascular bed.
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Authors | A M Lefer, M R Siegfried, X L Ma |
Journal | Journal of cardiovascular pharmacology
(J Cardiovasc Pharmacol)
Vol. 22 Suppl 7
Pg. S27-33
( 1993)
ISSN: 0160-2446 [Print] United States |
PMID | 7504765
(Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Sydnones
- Vasodilator Agents
- 3-(cis-2,6-dimethylpiperidino)sydnonimine
- Nitric Oxide
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Topics |
- Animals
- Cats
- Endothelium, Vascular
(drug effects, metabolism)
- Male
- Muscle, Smooth, Vascular
(drug effects)
- Neutrophils
(metabolism)
- Nitric Oxide
(metabolism)
- Reperfusion Injury
(metabolism, prevention & control)
- Sydnones
(therapeutic use)
- Vasodilator Agents
(therapeutic use)
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