Nonischemic myocardial damage induced by nonocclusive constriction of coronary artery in rats.

To determine whether reduction in coronary vessel diameter leads to alterations in cardiac function, coronary perfusion, and tissue integrity, the left coronary artery of rats was narrowed and ventricular hemodynamics measured at 3 and 5 days after surgery. Coronary artery narrowing averaged 62% and end-diastolic pressure was increased, whereas peak systolic pressure, positive change in pressure over time, stroke volume, and total peripheral resistance were decreased. However, this impairment of function was accompanied by a preservation of resting coronary blood flow (CBF), although a 43% decrease in maximal CBF was detected. Foci of reparative fibrosis and myocytolytic necrosis were found primarily in the endomyocardium and midmyocardium. These lesions were temporally distinct, corresponding to 5 days and 12- to 24-h-old forms of myocardial damage, respectively. The changes in maximal CBF correlated with the degree of stenosis, whereas the volume fraction, average cross-sectional area, and number of foci of reparative fibrosis lesions per unit area of myocardium correlated exclusively with end-diastolic pressure. In conclusion, reductions in luminal diameter of a major coronary artery not affecting resting coronary perfusion have a profound detrimental impact on cardiac performance and initiate immediate myocyte cell loss that is ongoing. Thus tissue and cellular damage may not be ischemic in nature but rather mediated by other mechanisms such as unbearable mechanical stress.