Early captopril prevents myocardial infarction-induced hypertrophy but not angiogenesis.

Delayed captopril, started after the healing phase of myocardial infarction, improves perfusion by reducing tissue weight without affecting the vascular capacity of the heart. Early captopril, during the healing phase, prevents reactive hypertrophy, but the effects on angiogenesis are unknown. Therefore, the effects of early captopril (2 g/l drinking water, from 1 day until 3 weeks after myocardial infarction) on regional coronary flow related to tissue mass, were studied in isolated perfused hearts from rats, subjected to coronary artery ligation. Regional maximal vascular capacity was measured during nitroprusside-induced vasodilation, using radioactive microspheres. Maximal vascular capacity was not changed by captopril. Reactive hypertrophy in infarcted hearts only reached statistical significance in the left ventricular free wall. Since captopril prevented hypertrophy but did not affect regional capacity, peak tissue perfusion was improved. Indicating effects on metabolism, captopril restored the increased lactate/purine ratio in infarcted hearts. Thus, early captopril treatment prevented post-myocardial infarction hypertrophy but did not suppress angiogenesis, thus beneficially influencing the vascularization/tissue mass ratio, probably reflected by preservation of aerobic metabolism.

Regionally different vascular response to vasoactive substances in the remodelled infarcted rat heart; aberrant vasculature in the infarct scar.

Remodelling after myocardial infarction (MI) is associated with vascular adaption, increasing vascular capacity of non-infarcted myocardium, and angiogenesis in the infarcted part during wound healing and scarring. We investigated regional vascular reactivity in the infarcted rat heart. Transmural infarction of the left ventricular free wall was induced by coronary artery ligation. After 3 weeks, regional flow during maximal vasodilation (nitroprusside, NPR) and submaximal vasoconstriction (arginine-vasopressin, AVP) were studied in buffer-perfused hearts. The main findings were: (1) a reduced vasodilator response (NPR) in the viable part of the left ventricular free wall, where hypertrophy was most pronounced, resulting in reduced maximal tissue perfusion of the myocardium bordering the scar (19.7 + 0.6 v 25.7 + 1.2 ml/min.g), whereas perfusion of other non-infarcted regions was preserved. (2) A 54% lower vasodilator response (NPR) and a 25% stronger vasoconstriction (AVP) in scar tissue compared to viable parts of MI hearts. Microscopy showed thicker walls of resistance arteries in scar tissue than in viable parts of MI hearts or in sham hearts, morphometrically substantiated by two- to three-fold greater wall/lumen ratios. These data indicate a deviant response of scar vessels of MI hearts, and in the non-infarcted part, a reduced coronary reserve in the most hypertrophied region. Whereas the former may be caused by different vessel structure, the reduced vasodilator reserve of the spared part of the left ventricular free wall may indicate vasodilation at rest due to insufficient vascular growth. Thus, the most hypertrophied region would be at the highest risk of further ischemic damage.

Determinants of coronary reserve in rats subjected to coronary artery ligation or aortic banding.

OBJECTIVE: We investigated whether decreased coronary reserve in hearts after coronary artery ligation or in hearts from rats after aortic banding can be related to remodeling of resistance arteries. METHODS: Maximal coronary flow (absolute flow) and cardiac perfusion (flow corrected for heart weight) were determined in isolated, perfused rat hearts after adenosine or nitroprusside, at 3 and 8 weeks after coronary artery ligation or 4-5 weeks after aortic banding. Perivascular collagen and medial thickness of resistance arteries were determined by morphometry. RESULTS: maximal coronary flow of infarcted hearts had been restored to sham values at 3 weeks. Growth of cardiac muscle mass from 3 to 8 weeks exceeded the increase in maximal coronary flow, leading to a decreased perfusion at 8 weeks. A slight, transient increase in perivascular collagen, but no medial hypertrophy, was found after infarction. After aortic banding perivascular fibrosis and medial hypertrophy led to a decreased maximal coronary flow in both the hypertrophied left and the non-hypertrophied right ventricle. Consequently, perfusion of the left ventricle was most severely reduced. CONCLUSIONS: Reduced maximal perfusion after aortic banding is determined by both cardiac hypertrophy and vascular remodeling. In contrast, during infarction-induced remodeling, reduction of perfusion is not determined by vascular remodeling, but mainly by disproportional cardiac hypertrophy relative to vascular growth.