Myocardial hypertrophy in the ischemic zone induced by exercise in rats after coronary reperfusion

Abstract

Background. Factors influencing left ventricular (LV) remodeling after coronary artery reperfusion, including adaptive changes in the infarcted region and the role of exercise, have not been well defined. The common application of early reperfusion by thrombolysis after acute myocardial infarction lends potential significance to such remodeling, and a rat model with 45 minutes of regional ischemia followed by reperfusion was developed to study these events. We postulated that the effects of reperfusion in altering LV morphology would be further modified by exercise training, including induction of hypertrophic changes in the outer region of the nontransmural infarction. Methods and Results. Female Sprague-Dawley rats were subjected either to 15 minutes of left anterior descending coronary artery occlusion followed by reperfusion or to sham operation, and at 5 days after the operation, animals were randomly assigned to sedentary conditions or to 3 weeks of swimming exercise. Animals completing the experiment included a reperfused sedentary group (n=21), a reperfused exercised group (n=20), a sham-operated group (n=10), and a sham-operated group subjected to exercise (sham exercised group, n=9). In addition, in seven rats, myocardial infarction was produced by permanent coronary occlusion, and the animals remained sedentary (permanent occlusion group). In each group, the morphology of the noninfarcted (septal) and the infarcted (anterolateral) regions of the left ventricle was examined 26 days after surgery from midventricular transverse sections 25 μm thick taken after perfusion fixation of the heart at an aortic pressure of 60 mm Hg and an LV cavity pressure of 10 mm Hg. Compared with the permanent occlusion group, LV cavity area in the sedentary reperfused group was smaller (33.5 versus 53.2 mm2, p<0.001), the infarcted wall was thicker (1.36 versus 0.53 mm, p<0.001), and the septal wall also was thicker (1.95 versus 1.62 mm, p<0.05), whereas compared with the sham-operated group, the LV cavity area was increased, and infarcted wall thickness was reduced (both p<0.01). Reperfusion resulted in less transmurality of infarction compared with permanent occlusion (38.3% versus 69.5%, p<0.001), with increased subepicardial area in the infarcted zone after reperfusion (7.5 versus 1.9 mm2, p<0.001). In the reperfused exercised group, transmurality was further decreased compared with the reperfused sedentary group (31.5% versus 38.3%, p<0.05), and the viable subepicardial area of the infarct zone increased by 32%. Conclusions. Important remodeling of global and regional LV morphology was evident at 26 days in sedentary rats after 45 minutes of coronary occlusion with reperfusion compared with rats with permanent coronary occlusion, with reduced infarct transmurality and less LV dilation in the reperfused group. Exercise after reperfusion further affected ventricular remodeling by causing hypertrophy with increased wall thickness of the surviving subepicardium of the infarcted zone.