Chronic nonocclusive coronary artery constriction impairs ventricular function, myocardial structure, and cardiac contractile protein enzyme activity in rats.

Abstract

To determine the effects of chronic nonocclusive coronary constriction on cardiac hemodynamics, structural integrity, and contractile protein enzyme activity, the left coronary artery was narrowed in rats, and measurements of ventricular performance, magnitude, and distribution of tissue damage and myofibrillar Mg2+ and Ca2+ myosin ATPase activities were evaluated 1 month later. In the presence of coronary artery stenosis averaging 58%, three levels of involvement of global cardiac performance were identified, and the rats were divided accordingly. In the first group, only left ventricular end-diastolic pressure (LVEDP) was increased; in the second group, LVEDP and left ventricular +dP/dt and/or -dP/dt were affected; and in the third group, LVEDP, left ventricular +dP/dt and -dP/dt, and right ventricular end-diastolic pressure were impaired. Thus, left ventricular moderate dysfunction, severe dysfunction, and failure occurred with coronary narrowing. On a structural basis, coronary constriction resulted in an ongoing process characterized by acute myocytolytic necrosis and foci of replacement fibrosis in different stages of healing. The number of these lesion profiles in the left ventricular myocardium increased 4.7-, 4.4-, and 8.3-fold in rats with moderate dysfunction, severe dysfunction, and failure, respectively. Biochemically, Mg(2+)-ATPase activity of myofibrils increased biventricularly when moderate dysfunction was present. However, this parameter decreased with the appearance of severe dysfunction, reaching control values in ventricular failure. Ca2+ myosin ATPase activity was reduced in the left ventricle of rats with severe dysfunction and failure, whereas it was elevated in the right ventricle of rats with severe dysfunction. In conclusion, a fixed lesion of the left main coronary artery with a modest reduction in vessel luminal diameter generates a conditioned state of the heart characterized by a continuous loss of myocytes and replacement scarring, which, in combination with alterations in contractile protein enzyme activity, may be responsible for a number of abnormalities in cardiac dynamics ranging from moderate dysfunction to pump failure.