Long‐Term Survival of Adult Cardiac Myocytes in Large Transmural Post‐Myocardial Infarction Scars Is Supported by a Functional, Local Microvascular Network

Abstract

The presence of surviving cardiac myocytes in post‐myocardial infarction (MI) scars has been repeatedly documented in humans as well as in various laboratory animals, particularly in rats. In the majority of cases, the long‐term survival of cardiac myocytes in post‐MI scars has been attributed either to continuing arterial blood supply from the bordering noninfarcted myocardium or to a rapid reestablishment of blood perfusion through the original coronary artery after a transient period of ischemia. On the other hand, in a rat model of chronic MI produced by permanent ligation of the left coronary artery, the persistent survival of adult cardiac myocytes in remote areas of the large transmural scar remains yet poorly understood. Considering the fact that in such model the left coronary artery remained permanently occluded for the duration of an entire experimental period, the presence of viable cardiac myocytes in mature scars has been often explained by simple diffusion of oxygen and nutrients from either the left ventricular (LV) cavity or large subepicardial veins. In order to test this hypothesis, in our current study, a special emphasis has been made on investigation of the regional microenvironment, particularly the source of nourishing blood supply, which could facilitate long‐term survival of adult cardiac myocytes in scars. A large transmural MI was induced in 12‐month‐old male Sprague‐Dawley rats by permanent ligation of the left coronary artery. The patency of residual blood vessels was assessed in vivo in 4‐, 8‐ and 12‐week‐old scars by infusion of 15‐micron microspheres into the LV cavity shortly before euthanasia. The hearts were collected 3 days, 1, 2, 4, 8 and 12 weeks after MI and evaluated with histology, immunohistochemistry and quantitative morphometry. We found that, at all time points, the large, transmurally infarcted/ scarred area had a sparse population of viable cardiac myocytes primarily localized in subendocardial and subepicardial regions. We also confirmed the finding that in the subepicardial region, the groups of surviving cardiac myocytes were often seen around large residual veins. However, further examination has revealed that all clusters of surviving cardiac myocytes were always associated with a network of patent microvessels, including capillaries, venules and arteriolar‐like vessels. Most importantly, the presence of microspheres in the venules of such microvascular networks has substantiated the concept that blood perfused through these microvessels was originated from the LV cavity. This hypothesis was further strengthen by the fact that the endocardial surface of some transmural scars revealed the presence of patent orifices from the Thebesian veins, suggesting that the remnants of the venous vascular system within the scars, including subendocardial and subepicardial venous plexuses as well as intramural venous sinusoids, could to some extent undergo retrograde perfusion with arterial blood. Taken together, our current findings suggest that long‐term survival of adult cardiac myocytes in large, transmural post‐MI scars is sustained by the local microcirculatory networks which are structurally and functionally coupled with the residual venous system that maintains direct connections with the cavity of the left ventricle.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.