Evolution of scar structure, mechanics, and ventricular function after myocardial infarction in the rat

Abstract

The mechanical properties of the healing scar are an important determinant of heart function following myocardial infarction. Yet the relationship between scar structure, scar mechanics, and ventricular function remains poorly understood, in part because no published study has tracked all of these factors simultaneously in any animal model. We therefore studied the temporal evolution of scar structure, scar mechanics, and left ventricular (LV) function in large anterior myocardial infarcts in rats. At 1, 2, 3, and 6 wk after left anterior descending coronary ligation, we examined LV function using sonomicrometry, infarct mechanical properties using biaxial mechanical testing, infarct structure using polarized light microscopy, and scar collagen content and cross-linking using biochemical assays. Healing infarcts in the rat were structurally and mechanically isotropic at all time points. Collagen content increased with time and was the primary determinant of scar mechanical properties. The presence of healing infarcts influenced systolic LV function through a rightward shift of the end-systolic pressure-volume relationship (ESPVR) that depended on infarct size, infarct collagen content, and LV dilation. We conclude that in sharp contrast to previous reports in large animal models, healing infarcts are structurally and mechanically isotropic in the standard rat model of myocardial infarction. On the basis of the regional strain patterns we observed in healing rat infarcts in this study and in healing pig infarcts in previous studies, we hypothesize that the local pattern of stretching determines collagen alignment in healing myocardial infarct scars.