Influence of Angiotensin II Type 1-Receptor Antagonist CV11974 on Infarct Size and Adjacent Regional Function After Ischemia-Reperfusion in Dogs

Abstract

The presence of nonischemic regional dysfunction at the adjacent region of the ischemic myocardium was demonstrated in clinical studies. Recent studies demonstrated an angiotensin II type 1 (AT₁)-receptor antagonist reduced myocardial ischemia-reperfusion injury. We investigated the role of the adjacent region after reperfusion by studying the effects of AT₁-receptor antagonist on myocardial function and infarct size. We investigated 12 open-chest anesthetized dogs undergoing 90 min of left anterior descending coronary artery occlusion followed by 4 h of reperfusion. Six dogs injected with an AT₁-receptor antagonist (CV11974) immediately after reperfusion were compared with 6 control dogs. Percent systolic shortening (%SS) was measured by two sets of the pair sonomicrometer crystals implanted to adjacent and remote nonischemic myocardium. After 4 h of reperfusion, infarct size was measured. There were no significant differences of the %SS at baseline between two regions. In both groups, %SS at adjacent region after reperfusion was significantly decreased as compared with remote region. There were no significant differences between the two groups. Infarct size, as a percentage of the area at risk, was smaller in the AT₁ group than in control group (25.49 ± 7.53% vs 68.58 ± 26.88% P<0.01). AT₁-receptor antagonist reduces infarct size. This effect is not related to the change of regional myocardial function at adjacent region after reperfusion.