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Am J Physiol Heart Circ Physiol (November 6, 2009). doi:10.1152/ajpheart.00495.2009
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Submitted on June 1, 2009
Revised on October 20, 2009
Accepted on November 3, 2009

Evolution of Scar Structure, Mechanics, and Ventricular Function after Myocardial Infarction in the Rat

Gregory M FOMOVSKY1 and Jeffrey W. Holmes1*

1 University of Virginia

* To whom correspondence should be addressed. E-mail: holmes{at}virginia.edu.

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 LV function in large anterior myocardial infarcts in rats. One, two, three, and six weeks after left coronary ligation, we examined left ventricular function using sonomicrometry, infarct mechanical properties using biaxial mechanical testing, infarct structure using polarized light microscopy, and scar collagen content and crosslinking 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. Based on 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.







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