Sex‐related differences in intrinsic myocardial properties influence cardiac function in middle‐aged rats during infarction‐induced left ventricular remodeling

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/mm 2 vs. 1785.7 ± 55.9 cells/mm 2 , 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/mm 2 vs. 0.91 ± 0.30 cells/mm 2 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.