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Murine Myocardial Infarction Model using Permanent Ligation of Left Anterior Descending Coronary Artery
Published on: August 16, 2019
Scar formation after ischemic myocardial injury in MRL mice
Yong-Seog Oh1, Louise E J Thomson, Michael C Fishbein
1Division of Cardiology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
Introduction:
MRL is a strain of mice with the unusual ability to recover from injuries without forming scar tissue. It was recently reported that the MRL mice can recover with little or no scar formation following a cryogenically induced myocardial infarction of the right ventricle. These findings suggest that scarless recovery from myocardial injury is possible in mammalian ventricles. If applicable to humans, these results could have significant clinical implications in the management of patients with myocardial infarction. However, myocardial infarction in human patients usually results from ischemic injury instead of cryoinjury. Myocardial infarction usually occurs in the left ventricle.
Methods:
We performed a prospective study creating left ventricular myocardial infarction in 32 MRL mice using coronary ligation.
Results:
Among them, 21 mice survived surgery and had myocardial infarction documented by delayed contrast-enhanced magnetic resonance imaging (MRI) 35+/-10 days after surgery. All 21 mice had evidence of myocardial infarction in follow-up MRI performed 116+/-21 days after surgery. The infarct size was 27+/-12% of the area of visualized myocardium during the first MRI study and was 29+/-11% during the second MRI study (P=NS). Large myocardial infarction with aneurysm formation was documented by histological examinations in all 21 mice. The ventricular aneurysm showed transmural infarction with replacement fibrosis and mummified necrotic myocardium surrounded by collagenous scar tissue. Occasional surviving myocytes are present within the aneurysm.
Conclusion:
Ischemic myocardial injury in MRL mice is not followed by scarless recovery.
Insights
Scarless healing in MRL mice, known for injury repair without scarring, was investigated for ischemic myocardial infarction. These mice did not exhibit scarless recovery following left ventricular myocardial infarction, indicating limitations in this model for studying myocardial repair.
Area of Science:
- Cardiovascular Research
- Regenerative Medicine
- Mammalian Models
Background:
- MRL mice exhibit remarkable scarless healing capabilities after injury.
- Previous studies indicated scarless recovery from cryoinjury-induced myocardial infarction in the right ventricle of MRL mice.
- This suggests potential for scarless myocardial repair in mammalian ventricles, with implications for human myocardial infarction (MI).
Purpose of the Study:
- To investigate scarless recovery following ischemic myocardial infarction in the left ventricle of MRL mice.
- To determine if the scarless healing observed in MRL mice extends to ischemic MI, which is more relevant to human conditions.
Main Methods:
- A prospective study involving 32 MRL mice was conducted.
- Left ventricular myocardial infarction was induced using coronary ligation.
- Delayed contrast-enhanced magnetic resonance imaging (MRI) and histological examinations were used to assess infarct size and tissue characteristics.
Main Results:
- 21 mice survived surgery and were confirmed to have myocardial infarction via MRI.
- Infarct size remained consistent between early and late follow-up MRIs (27% and 29%, respectively).
- Histological examination revealed large myocardial infarction with aneurysm formation, characterized by transmural infarction, fibrosis, and scar tissue, not scarless healing.
Conclusions:
- Ischemic myocardial injury in MRL mice does not result in scarless recovery.
- The MRL mouse model, while capable of scarless healing in other contexts, does not replicate scarless repair for ischemic left ventricular myocardial infarction.
