Clentiazem given at reperfusion improves subendocardial reflow and reduces myocardial infarct size in the dog

G Rousseau, P Provost, D Tran, G Caille and JG Latour

Laboratory of Experimental Pathology, Montreal Heart Institute, University of Montreal, Quebec, Canada.

The postischemic cardioprotection by calcium antagonists and the interplay between neutrophils and regional myocardial blood flow were investigated further, using clentiazem, a new potent calcium channel blocker derived from diltiazem. A 90-min occlusion of the interventricular coronary artery was followed by 6 hr of reperfusion in anesthetized dogs. One group was given clentiazem: 100 micrograms/kg at 5 min before reperfusion followed by a perfusion of 1 microgram/kg/min until sacrifice; controls received saline. Infarct size (% of area at risk) estimated with triphenyltetrazolium staining and by histology was reduced by nearly 50% (P < .05) in treated (16.6 +/- 3.0%), as compared to control (31.6 +/- 6.3%) dogs. Regional and collateral myocardial flows estimated with radioactive microspheres were similar between groups before and during occlusion. However, after an initial recovery to preocclusion values at 30-min reperfusion in both groups, flow declined to 50% normal (P < .05) in control animals after 3 and 6 hr in midwall and subendocardium, but the change was remarkably attenuated (P < .05) in subendocardium of clentiazem-treated dogs. Also, neutrophil accumulation at the epicardial side of the infarct, at the edge of salvaged myocardium, and estimated by tissue myeloperoxidase measurement, was reduced by 50% in treated dogs (clentiazem: 17.2 +/- 2.8; controls: 32.3 +/- 2.7 x 10(6) neutrophils/g). We conclude that administration of clentiazem at reperfusion reduces infarct size by interfering with both neutrophil accumulation and development of subendocardial no reflow in reperfused myocardium.

Volume 268, Issue 3, pp. 1252-1260, 03/01/1994
Copyright © 1994 by American Society for Pharmacology and Experimental Therapeutics

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