CORONARY-ARTERY NARROWING IN RATS - MECHANICAL ALTERATIONS OF LEFT AND RIGHT MYOCARDIUM

To determine the effects of chronic coronary artery narrowing on myocardial contractile performance, nonocclusive constriction of the left coronary artery near its origin was surgically induced in rats and global cardiac hemodynamics, left and right myocardial mechanics, and the magnitude and distribution of tissue damage and interstitial fibrosis in the left ventricular wall were analyzed 1 mo later. Reductions in coronary artery luminal diameter of 55% resulted in left ventricular failure as characterized by decreases in systemic arterial pressures, systolic ventricular pressure, rise and decay in first derivative of left ventricular pressure (+/- dP/dt), and an increase in left ventricular end-diastolic pressure. Right side dysfunction was also present as documented by an elevation in right ventricular end-diastolic pressure and a reduction in -dP/dt. In vitro measurements of papillary muscle mechanics revealed a biventricular reduction in isometric developed tension and peak rates of tension rise and decay. Moreover, the kinetic parameters of isometric contraction duration, time to peak tension and time to one-half relaxation, were significantly shorter in left muscles from coronary artery-narrowed animals. Isotonically, peak muscle shortening was reduced in the left muscle, whereas time to peak shortening was prolonged in the right myocardium. In addition, the velocities of muscle shortening and relengthening were decreased in both ventricles. Foci of replacement fibrosis and diffuse interstitial fibrosis were found in the epimyocardium, midmyocardium, and endomyocardium, demonstrating that a significant amount of myocyte loss occurred throughout the left ventricular wall. In conclusion, a fixed lesion of a major epicardial coronary artery engenders alterations in myocardial contractile behavior and myocyte loss with scarring, which appear to be major determinants in the genesis of cardiac dysfunction and failure in this animal model.