Cardiovascular Research

Deterioration in myocardial blood flow following relief of sustained ischemia is not associated with release of endothelin into

Authors: K Przyklenk|||B Z Simkhovich|||B Bauer|||R A Kloner

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Abstract

Numerous studies have described a progressive deterioration in resting myocardial blood flow following relief of sustained ischemia in both necrotic and salvaged myocardium (termed "no reflow" and "low reflow", respectively). We sought to determine whether release of the potent vasoconstrictor peptide endothelin-1 may play a role in these phenomena. As part of a previous study in our laboratory, 14 anesthetized open-chest dogs underwent 1 h of coronary artery occlusion and 4 h of reperfusion, while 2 dogs served as time-matched sham-operated controls (artery isolated but not occluded). Regional myocardial blood flow was measured by injection of radiolabeled microspheres at 30 min and 4 h post reflow; endothelin-1 concentrations in the coronary sinus were determined by radioimmunoassay at baseline, during coronary occlusion and at 30 min and 4 h after reperfusion; and the extent of myocardial necrosis was delineated by post-mortem tetrazolium staining. As expected, in dogs subjected to ischemia/reperfusion, regional myocardial blood flow deteriorated between 30 min and 4 h post reflow in both the subendocardium (1.40 +/- 0.30 versus 0.48 +/- 0.06 ml/min/g; p = 0.003; reflecting a mixture of no reflow and low reflow) and subepicardium (0.84 +/- 0.08 versus 0.64 +/- 0.07 ml/min/g; p = 0.03; due to low reflow). However, endothelin levels showed only a modest and nonsignificant increase during the protocol (4.1 +/- 0.5, 4.7 +/- 0.2 and 4.9 +/- 0.6 pg/ml plasma at baseline, 30 min and 4 h post reflow; p = NS), and regression analysis revealed no correlation between release of endothelin and deterioration in blood flow in either myocardial layer. Moreover, the sham-operated controls showed a similar modest increase in endothelin levels, with no change in myocardial perfusion during the course of the protocol. We therefore conclude that deterioration in myocardial blood flow following relief of sustained ischemia in the anesthetized open-chest dog is not associated with release of endothelin-1 into the coronary sinus.

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Chemical List

Endothelins

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Reference List

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