ArticleSudden obstruction of coronary blood flow causes ischemic death of cardiomyocytes followed by a universal cascade of reparative events (Frangogiannis 2006) leading to infarct healing and scar formation in the heart. Nevertheless, a growing body of evidence from animal studies suggests that females exhibit a different pattern of myocardial infarction (MI) healing and left ventricular (LV) remodeling than males. For instance, post-MI female mice reveal less exaggerated inflammation and enhanced reparative fibrotic response during infarct healing, contributing to a lower rate of cardiac rupture and a lesser degree of LV remodeling in comparison with males (Cavasin et al. 2004;Gao et al. 2005;Fang et al. 2007;Wang F et al. 2007). In addition, despite comparable infarct size and LV cavity dilatation, the thickness of noninfarcted myocardium is less in post-MI female than male rats (Litwin et al. 1999), indicating a smaller increase in compensatory hypertrophy in response to post-MI cardiac remodeling in the females.Although most of these studies were focused on earlier reparative events taking place in male and female hearts during the overlapping phases of MI healing (i.e., inflammatory, proliferative and maturation phases), surprisingly little attention has been paid to providing a comparative assessment of the structural components in a mature scar. However, it has been previously shown that the tissue composition of a mature scar is an important determinant of its mechanical properties (Connelly et al. 1985) and, thereby, can drastically influence overall ventricular performance SummaryThe present study was designed to determine whether the structural composition of the scar in middle-aged post-myocardial infraction (MI) rats is affected by the biological sex of the animals. A large MI was induced in 12-month-old male (M-MI) and female (F-MI) Sprague-Dawley rats by ligation of the left coronary artery. Four weeks after the MI, rats with transmural infarctions, greater than 50% of the left ventricular (LV) free wall, were evaluated. The extent of LV remodeling and fractional volumes of fibrillar collagen (FC), myofibroblasts, vascular smooth muscle (SM) cells, and surviving cardiac myocytes (CM) in the scars were compared between the two sexes. The left ventricle of post-MI male and female rats underwent a similar degree of remodeling as evidenced by the analogous scar thinning ratio (0.46 ± 0.02 vs. 0.42 ± 0.05) and infarct expansion index (1.06 ± 0.07 vs. 1.12 ± 0.08), respectively. Most important, the contents of major structural components of the scar revealed no evident difference between M-MI and F-MI rats (interstitial FC, 80.74 ± 2.08 vs. 82.57 ± 4.53; myofibroblasts, 9.59 ± 1.68 vs. 9.56 ± 1.15; vascular SM cells, 2.27 ± 0.51 vs. 3.38 ± 0.47; and surviving CM, 3.26 ± 0.39 vs. 3.05 ± 0.38, respectively). Our data are the first to demonstrate that biological sex does not influence the structural composition of a mature scar in middleaged post-MI rats. (J Histochem Cytochem 61:833-848, 2013)

This study was aimed to understand the mechanism of persistent cardiac myocyte (CM) survival in myocardial infarction (MI) scars. A transmural MI was induced in 12-month-old Sprague-Dawley rats by permanent coronary artery ligation. The hearts were collected 3 days, 1, 2, 4, 8, and 12 weeks after MI and evaluated with histology, immunohistochemistry, and quantitative morphometry. Vasculature patency was assessed in 4-, 8-, and 12-week-old scars by infusion of 15-micron microspheres into the left ventricle before euthanasia. The infarcted/scarred area has a small continually retained population of surviving CMs in subendocardial and subepicardial regions. Surprisingly, whereas the transverse area of subepicardial CMs remained relatively preserved or even enlarged over 12 post-MI weeks, subendocardial CMs underwent progressive atrophy. Nevertheless, the fractional volume of viable CMs remained comparable in mature scars 4, 8, and 12 weeks after MI (3.6 ± 0.4%, 3.4 ± 0.5%, and 2.5 ± 0.3%, respectively). Despite the opposite dynamics of changes in size, CMs of both regions displayed sarcomeres and gap junctions. Most importantly, surviving CMs were always accompanied by patent microvessels linked to a venous network composed of Thebesian veins, intramural sinusoids, and subepicardial veins. Our findings reveal that long-term survival of CMs in transmural post-MI scars is sustained by a local microcirculatory bed.

We previously determined that residual left ventricular (LV) myocardium of middle‐aged rats had sex‐related differences in regional tissue properties 4 weeks after a large myocardial infarction (MI). However, the impact of such differences on cardiac performance remained unclear. Therefore, our current study aimed to elucidate whether sex‐related changes in MI‐induced myocardial remodeling can influence cardiac function. A similar‐sized MI was induced in 12‐month‐old male (M‐MI) and female (F‐MI) Sprague–Dawley rats by ligation of the left coronary artery. The cardiac function was monitored for 2 months after MI and then various LV parameters were compared between sexes. We found that although two sex groups had a similar pattern of MI‐induced decline in LV function, F‐MI rats had greater cardiac performance compared to M‐MI rats, considering the higher values of EF (39.9 ± 3.4% vs. 26.7 ± 7.7%, P < 0.05), SW index (40.4 ± 2.1 mmHg • mL/kg vs. 20.2 ± 3.3 mmHg • mL/kg, P < 0.001), and CI (139.2 ± 7.9 mL/min/kg vs. 74.9 ± 14.7 mL/min/kg, P < 0.01). The poorer pumping capacity in M‐MI hearts was associated with markedly reduced LV compliance and prolonged relaxation. On the tissue level, F‐MI rats revealed a higher, than in M‐MI rats, density of cardiac myocytes in the LV free wall (2383.8 ± 242.6 cells/mm2 vs. 1785.7 ± 55.9 cells/mm2, P < 0.05). The latter finding correlated with a lower density of apoptotic cardiac myocytes in residual LV myocardium of F‐MI rats (0.18 ± 0.08 cells/mm2 vs. 0.91 ± 0.30 cells/mm2 in males, P < 0.01). Thus, our data suggested that F‐MI rats had markedly attenuated decline in cardiac performance compared to males due to ability of female rats to better retain functionally favorable intrinsic myocardial properties.

Our data reveal that chronic IVA-induced HRR does not provide sustainable benefits for LV systolic performance in middle-aged rats with post-MI HF.

Our previous study on post‐MI male and female middle‐aged rats has revealed the regional sex‐specific differences in the adaptive changes of the left ventricular (LV) cardiac myocytes and coronary vessels. However, the impact of such structural alterations on LV systolic properties remained unclear. Therefore, our current study is aimed to determine whether post‐MI cardiac remodeling in middle‐aged rats associates with sex‐related differences in LV systolic performance, function or contractility. A large MI was induced in 12‐month‐old male (M‐MI) and female (F‐MI) Sprague‐Dawley rats by ligation of the left coronary artery. Two months after the surgery, the various LV parameters were compared between the sexes using echocardiography, hemodynamics and morphometry. We found that although both sexes had a similar scale of global post‐MI LV remodeling, the F‐MI rats showed a significantly lesser degree of cardiac myocyte hypertrophy in the epimyocardium compared to males (353.3±21.4 vs. 479.0±20.6 μm², P蠄0.01). Nevertheless, rats in M‐MI and F‐MI groups demonstrated comparable values of stroke volume (0.23±0.03 vs. 0.17±0.02 mL), ejection fraction (28.1±3.9 vs. 38.68±4.74 %) and peak dP/dt (3068.3±240.6 vs. 3307.0±214.1 mmHg/sec). Thus, our data reveal that male and female middle‐aged rats have a similar degree of deterioration in LV systolic properties associated with cardiac remodeling after a large MI.