The impact of pericardial disruption on heart function and remodeling after myocardial infarction in mice

Myocardial infarction (MI) remains a leading cause of deaths globally. Thus, reliable and relevant animal MI models are crucial to understand underlying disease mechanisms and develop new therapies. Generally, MI in rodents is induced by ligation of the left anterior descending artery (LAD) leaving a ruptured pericardium. This contrasts MI in man, where the pericardium remains intact. Herein, we therefore determined in adult mice whether pericardial disruption along MI influences left ventricular (LV) heart function, remodeling, and scar formation. Baseline heart function was assessed in 30 C57BL/6J adult, female mice, using state-of-the-art ultra-high-resolution ultrasound imaging (Vevo F2). After one week, MI was randomly introduced by LAD in two groups of mice with or without rupturing the pericardium. Functional heart recovery was evaluated 1- and 10 weeks post-MI, whereas success of MI introduction, animal survival, and scarring were quantified at week 10 by Masson's Trichrome histology and compared between groups. The success of MI introduction as well as mouse survival was equal between groups (p > 0.05). Cohort baseline data revealed normal heart function (55.9 ± 4.5% ejection fraction (EF), 33.3 ± 3.2% fractional shortening (FS), 23.3 ± 4.2 µL end-systolic volume (ESV), 52.5 ± 5.1 µL end-diastolic volume (EDV) and 29.2 ± 2.1 µL stroke volume (SV) (mean, SD, n = 21)). At 1-week post-MI, all mice exhibited significant (all p < 0.05) systolic dysfunction, which persisted at 10-weeks post-MI (46.8 ± 7.4%- vs. 49.3 ± 10.0% EF, 24.7 ± 6.3%- vs. 24.7 ± 5.6% FS, and 35.7 ± 12.8 µL- vs. 37.0 ± 14.9 µL ESV for intact and ruptured pericardium, respectively (mean, SD, n = 9 and 12)) with no major differences between groups (all p > 0.05). For ruptured pericardium, we did see a slight increase in EF and SV from week 1 to 10. Ventricular remodeling was equally evident in both groups, with increased (all p > 0.05) LV mass and end-systolic- and end-diastolic area, but no difference (all p > 0.05) between groups. A mild increase in LV posterior wall thickness was exclusively apparent for ruptured pericardium, whereas anterior wall thickness was similar between groups. In line, infarct size was similar between groups (p > 0.05). Pericardial integrity does not universally alter heart function and scar size following LAD ligation in adult female mice, but may have some previously unnoticed compensatory effects not present after MI in man and that should be considered when modeling MI in the mouse.