Calcium-activated neutral protease inhibitor(E-64c) and reperfusion for experimental myocardial infarction.

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We examined the efficacy of the combination of coronary reperfusion and calcium-activated neutral protease (CANP) inhibitor (E-64c) for the treatment of acute myocardial infarction in dogs. In 34 dogs, the left anterior descending artery (LAD) was occluded and reperfused after 1 hour (Groups A and B). In the remaining 49 dogs, the LAD was ligated (Groups C and D). E-64c (100mg/kg, Groups A and C) or vehicle (Groups B and D) was injected intravenously before and after the coro-nary occlusion or ligation. After 24 hours the hearts were removed.The proportion of the infarct size in the LAD perfusing area (risk zone) in Group A was 47.3±9.7%, significantly lower than in Group C (54.8±8.2%, p<0.05) or Group D (58.7±10.0%, p<0.01). There was a significant difference between Group B (52.9±8.6%) and Group D as well (p<0.05). The effects of reperfusion (p=0.0016) and E-64c (p=0.0226) per se on infarct size were significant, but the combination of reperfusion and E-64c was not additive. The decrease in CPK activity in the risk zone was significantly lower in the reperfused group (p=0.0001). The mCANP activity was higher in the border zone and lower in the infarct zone. The trend in the μCANP activity was similar to that of mCANP.Thus, treatment with a CANP inhibitor in the early phase of acute myocardial infarction may be marginally beneficial in combination with reperfusion.
International Heart Journal刊行会の論文