CLENTIAZEM GIVEN AT REPERFUSION IMPROVES SUBENDOCARDIAL REFLOW AND REDUCES MYOCARDIAL INFARCT SIZE IN THE DOG

The postischemic cardioprotection by calcium antagonists and the inter play between neutrophils and regional myocardial blood flow were inves tigated further, using clentiazem, a new potent calcium channel blocke r derived from diltiazem. A 90-min occlusion of the interventricular c oronary artery was followed by 6 hr of reperfusion in anesthetized dog s. One group was given clentiazem: 100 mu g/kg at 5 min before reperfu sion followed by a perfusion of 1 mu g/kg/min until sacrifice; control s received saline. Infarct size (% of area at risk) estimated with tri phenyltetrazolium 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 r adioactive microspheres were similar between groups before and during occlusion. However, after an initial recovery to preocclusion values a t 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 epic ardial side of the infarct, at the edge of salvaged myocardium, and es timated by tissue myeloperoxydase measurement, was reduced by 50% in t reated dogs (clentiazem: 17.2 +/- 2.8; controls: 32.3 +/- 2.7 x 10(6) neutrophils/g). We conclude that administration of clentiazem at reper fusion reduces infarct size by interfering with both neutrophil accumu lation and development of subendocardial no reflow in reperfused myoca rdium.