Voluntary wheel running after myocardial infarction increases exercise capacity in female mice with minimal impact on left ventricular dilation

BACKGROUND: After a myocardial infarction (MI), the heart remodels as surviving myocardium compensates for the loss of functional tissue and elevated ventricular wall stress. This post-MI remodeling is characterized by left ventricular (LV) dilation and ensuing cardiac dysfunction. Severe LV dilation is associated with poor patient outcomes—such as exercise intolerance—and often portends the development of symptomatic heart failure. Exercise, which prompts physiologic cardiac remodeling, presents a promising therapeutic strategy for mitigating this structural and functional decline. OBJECTIVE: The objective of this study is to determine the impact of exercise on the structural remodeling and functional decline caused by MI in female mice. Given that male and female hearts respond distinctly to the remodeling stimuli of MI and exercise, only female mice were included in the present study. We hypothesize that exercise attenuates cardiac dysfunction linked to post-MI LV dilation and promotes remodeling outcomes that are conducive to improvements to exercise capacity. METHODS AND RESULTS: Female C57BL/6J mice, 16 to 21 weeks of age, were subjected to non-reperfused occlusion of the left coronary artery to induce MI. Four days later, echocardiography was performed, and mice with LV ejection fraction under 40% were randomized to exercise (EXE; n=11) or sedentary (SED; n=13) groups the next day. EXE mice were given continuous access to voluntary exercise wheels. Echocardiography was repeated after five weeks of EXE or SED conditions. Mice performed treadmill running-based exercise capacity tests (ECTs) before MI and five weeks after MI. Five weeks after MI, female EXE mice had similar LV volumes compared to SED controls. EXE mice had greater atrial weights (p=0.0435) than SED mice; however, no differences in mid-LV wall thicknesses were observed on M-mode echocardiography. Voluntary post-MI exercise did not impact functional metrics of ejection fraction, stroke volume, and cardiac output at rest. Despite similar LV dysfunction, EXE mice had increased work capacity by the five-week ECT (p< 0.0001), with an average work output of 28 joules (J) compared to the SED group’s average of 4.8 J. CONCLUSIONS: Although voluntary running did not mitigate post-MI LV dilation in female mice, it enhanced exercise tolerance. Further studies will determine the relative contributions of peripheral skeletal muscle versus cardiopulmonary adaptations to this effect. Disclosure of funding sources: We acknowledge NIH support (P30 GM127607, S10 OD038345, and R01 HL163272), and the Jewish Heritage Fund for Excellence. The content is solely the responsibility of the authors and may not represent views of the funding agencies. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.