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Myocardial infarction and remodeling in mice: effect of reperfusion
L H Michael1, C M Ballantyne, J P Zachariah
1DeBakey Heart Center and Department of Medicine, Baylor College of Medicine, Houston, Texas 77030-3498, USA. lmichael@bcm.tmc.edu
Abstract:
Anatomic and functional changes after either a permanent left anterior descending coronary artery occlusion (PO) or 2 h of occlusion followed by reperfusion (OR) in C57BL/6 mice were examined and compared with those in sham-operated mice. Both interventions generated infarcts comprising 30% of the left ventricle (LV) measured at 24 h and equivalent suppression of LV ejection velocity and filling velocity measured by Doppler ultrasound at 1 wk. Serial follow-up revealed that the ventricular ejection velocity and filling velocity returned to the levels of the sham-operated controls in the OR group at 2 wk and remained there; in contrast, PO animals continued to display suppression of both systolic and diastolic function. In contrast, ejection fractions of PO and OR animals were depressed equivalently (50% from sham-operated controls). Anatomic reconstruction of serial cross sections revealed that the percentage of the LV endocardial area overlying the ventricular scar (expansion ratio) was significantly larger in the PO group vs. the OR group (18 +/- 1.7% vs. 12 +/- 0.9%, P < 0.05). The septum that was never involved in the infarction had a significantly (P < 0.002) increased mass in PO animals (22.5 +/- 1.08 mg) vs. OR (17.8 +/- 1.10 mg) or sham control (14.8 +/- 0.99 mg) animals. Regression analysis demonstrated that the extent of septal hypertrophy correlated with LV expansion ratio. Thus late reperfusion appears to reduce the degree of infarct expansion even under circumstances in which it no longer can alter infarct size. We suggest that reperfusion promoted more effective ventricular repair, less infarct expansion, and significant recovery or preservation of ventricular function.
Insights
Early reperfusion after heart attack significantly improves ventricular repair and function. This study shows that restoring blood flow limits infarct expansion and preserves systolic and diastolic function in mice.
Area of Science:
- Cardiovascular Research
- Myocardial Infarction
- Cardiac Remodeling
Background:
- Myocardial infarction (MI) leads to infarct expansion and impaired cardiac function.
- The role of reperfusion in mitigating long-term adverse cardiac remodeling after MI requires further investigation.
Purpose of the Study:
- To compare the long-term anatomic and functional consequences of permanent left anterior descending coronary artery occlusion (PO) versus 2-hour occlusion followed by reperfusion (OR) in a mouse model.
- To investigate the impact of reperfusion on infarct expansion, septal hypertrophy, and ventricular function post-MI.
Main Methods:
- Induction of myocardial infarction via permanent (PO) or transient (OR) coronary artery occlusion in C57BL/6 mice.
- Assessment of infarct size, left ventricular (LV) ejection fraction, and systolic/diastolic function using Doppler ultrasound and anatomic reconstruction.
- Serial follow-up to evaluate functional recovery and structural changes over time.
Main Results:
- Both PO and OR groups exhibited equivalent infarct sizes (30% of LV) and initial ejection fraction depression (50%).
- The OR group showed recovery of LV ejection and filling velocities by 2 weeks, while the PO group exhibited persistent systolic and diastolic dysfunction.
- Infarct expansion (expansion ratio) and septal hypertrophy were significantly greater in the PO group compared to the OR group.
Conclusions:
- Late reperfusion significantly reduces infarct expansion and preserves systolic and diastolic function, even when infarct size is unchanged.
- Reperfusion promotes more effective ventricular repair, leading to better long-term cardiac function.
- Septal hypertrophy is correlated with infarct expansion, highlighting the detrimental effects of ongoing adverse remodeling in the absence of reperfusion.