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Published on: April 17, 2021
Acute, High Dose Metformin Therapy at Reperfusion Decreases Infarct Size in the High-Risk Aging Heart
Lauryn Bates1, Meredith Krause-Hauch1, Hao Wang1
1Department of Surgery, Morsani College of Medicine, University of South Florida, Tampa, FL, USA.
Insights
Elderly patients experiencing ST-elevation myocardial infarction (STEMI) face higher risks. Acute high-dose metformin at reperfusion reduced infarct size and improved heart function in aging mice, showing potential cardioprotection.
Area of Science:
- Cardiology
- Gerontology
- Pharmacology
Background:
- Elderly patients (>75 years) with ST-elevation myocardial infarction (STEMI) experience larger infarcts and higher mortality, even with reperfusion therapy.
- Advanced age is an independent risk factor for adverse outcomes in STEMI, irrespective of clinical and angiographic factors.
- This high-risk demographic may require additional treatments beyond reperfusion alone to improve outcomes.
Purpose of the Study:
- To investigate whether acute, high-dose metformin administration at reperfusion offers additional cardioprotection in an aging population.
- To test the hypothesis that metformin can modulate cardiac signaling and metabolism to reduce myocardial damage in elderly STEMI patients.
Main Methods:
- Utilized a translational aging murine model (22-24-month-old C57BL/6J mice).
- Induced in vivo ST-elevation myocardial infarction (STEMI) via 45 minutes of coronary artery occlusion followed by 24 hours of reperfusion.
- Administered high-dose metformin acutely at the time of reperfusion.
Main Results:
- Metformin treatment significantly decreased infarct size in the aging murine model.
- High-dose metformin enhanced cardiac contractile recovery following myocardial infarction.
- These findings demonstrate a cardioprotective effect of metformin in the aging heart during STEMI.
Conclusions:
- Acute high-dose metformin administration at reperfusion provides significant cardioprotection in a preclinical model of aging and myocardial infarction.
- Metformin may represent a valuable adjunctive therapy for elderly STEMI patients, improving outcomes beyond standard reperfusion treatments.
Abstract:
Elderly patients (age > 75) sustain larger infarcts with greater mortality from ST elevation myocardial infarcts (STEMI) despite successful reperfusion treatment. Elderly age remains an independent risk despite correction for clinical and angiographic variables. The elderly represent a high-risk population and may benefit from treatment in addition to reperfusion alone. We hypothesized that modulation of cardiac signaling and metabolism with acute, high dose metformin given at reperfusion would exhibit additional cardioprotection. Using a translational aging murine model (22-24-month C57BL/6J mice) of in vivo STEMI (45 min artery occlusion with reperfusion for 24 hours); treatment acutely at reperfusion by high dose metformin decreased infarct size and enhanced contractile recovery, demonstrating cardioprotection in the high-risk aging heart.
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