Myocardial Infarct Evolution and Cardiac Remodeling in Mice
A mouse model of myocardial infarction (MI) has been widely used since genetically engineered mice became available, which allows us to study gene regulation of cardiac phenotype, function, and pathophysiology of heart failure. However, some basic information, such as the healing process, infarct expansion and LV remodeling after MI in mice, is lacking. To clarify this process, 42 male C57B1/6J mice underwent coronary artery ligation and were killed at 1, 2, 4, or 7 days, or 2, 3, or 4 weeks after MI. Left ventricular (LV) morphology and function were evaluated by histopathology and echocardiography. We found that at the margin of the necrotic myocardium, infiltration by neutrophils was noticeable at 1 and 2 days. Marked infiltration by mononuclear cells occurred at day 4. Lymphocyte infiltration was apparent at 7 and 14 days. Massive proliferation of fibroblasts and fibrocytes and accumulation of collagen began at day 14 and scar formation was completed by day 21. The infarct expansion index increased gradually from 0.62 ± 0.12 at day 1 to 1.66 ± 0.35 at day 14, which reached a maximum, then decreased slightly to 1.51 ± 0.26 at day 28. In non-infarcted areas of the heart, myocyte cross-sectional area and collagen content increased from 161 ± 17 μm2 and 5.7 ± 0.3% at day 1 to 252 ± 8 μm2 and 10.8 ± 0.8% at day 21, respectively, and remained similar at day 28. Infarct size was 47%, 52% and 47% at day 1, 14 and 28 respectively. Increased LV diastolic chamber dimension and mass and decreased shortening fraction (SF) appeared as early as 2 weeks after MI and continued for 4 weeks (table). Thus this study provides important qualitative and quantitative information on the natural history of MI and validation of the mouse model.