Abstract Body: Introduction: Myocardial infarction (MI) leads to functional and structural deterioration in the left ventricle (LV). Understanding the relationship between LV biomechanical remodeling and cardiac decompensation post-MI relies on models that can consistently produce a wide spectrum of LV remodeling, including both mild and severe levels. This study presents an MI animal model to investigate LV biomechanical remodeling at two levels of infarct severity, myocardial stress, and ejection fraction (EF) over time, which is critical for assessing LV biomechanics-function relationship post-MI.
Method: MI was induced in male, 8-week-old WKY rats (n=6) by ligating the left anterior descending (LAD) artery at different locations. Severe MI was created by ligation within 2 mm below the left atrium (LA), while mild MI was induced 3–4 mm below the LA (Figs. 1A, B). EF was measured using echocardiography before and after MI. Biaxial mechanical testing assessed circumferential and longitudinal myocardial stresses, and anisotropy was calculated as the circumferential-to-longitudinal stress ratio. The impact of infarct severity was evaluated by comparing EF, myocardial stress, and anisotropy trends at 2- and 4-week post-MI relative to sham. Statistical analyses were performed to quantify these trends and assess the progression of biomechanical remodeling.
Results: EF for both mild and severe MI groups tended to show a progressive decline over time, with a greater reduction in severe MI (Fig. 1C). Myocardial anisotropy was the highest in sham and tended to decrease with infarct severity, with the lowest value observed in severe MI at 4-week post-MI (Fig. 1D). The loss of tissue anisotropy was driven by an increase in longitudinal stresses compared to sham. These increases were more pronounced in severe MI compared to mild MI (Fig. 1E).
Conclusion: Animal models with a controllable severity of MI are needed to determine the LV biomechanical mechanisms driving LV decompensation post-MI. Severe MI, with a greater EF reduction, exhibited a more pronounced loss of tissue anisotropy compared to mild MI. Future studies will examine the potential role of diminishing tissue anisotropy in triggering LV decompensation post-MI.