VENTRICULAR REMODELING IN GLOBAL-ISCHEMIA

To determine the effects of chronic constriction of the left coronary artery on the function and structure of the heart, coronary artery nar rowing was surgically induced in rats and ventricular pump performance , extent and distribution of myocardial damage, and the hypertrophic a nd hyperplastic response of myocytes were examined. Alterations in car diac hemodynamics were found in all rats, but the characteristics of t he physiological properties of the heart allowed a separation of the a nimals into two groups which exhibited left ventricular dysfunction an d failure, respectively. Left ventricular hypertrophy occurred in both groups and was characterized by ventricular dilatation and wall thinn ing which were more severe in the failing animals. Multiple foci of my ocardial damage across the wall were seen in all animals but tissue in jury was more prominent in the endomyocardium and in failing rats. The anatomical and hemodynamic changes resulted in a significant increase in diastolic wall stress which paralleled the depression in ventricul ar performance. Myocyte cell loss and myocyte cellular hypertrophy wer e more severe with ventricular failure than with dysfunction. Finally, diastolic overload appeared to be coupled with activation of the DNA synthetic machinery of myocytes and nuclear mitotic division, In concl usion, a fixed lesion of the left coronary artery leads to abnormaliti es in cardiac dynamics with marked increases in diastolic wall stress and extensive ventricular remodeling in spite of compensatory myocyte cellular hypertrophy and hyperplasia in the remaining viable tissue.