Metformin prevents ischaemic ventricular fibrillation in metabolically normal pigs

Diabetologia
Li LuGregory G Schwartz

Abstract

Metformin is the drug most often used to treat type 2 diabetes. Evidence suggests that metformin may reduce mortality of individuals with type 2 diabetes, but the mechanism of such an effect is unknown and outcomes of metformin treatment in people without diabetes have not been determined. If metformin favourably affected mortality of non-diabetic individuals, it might have even broader therapeutic utility. We evaluated the effect of metformin on myocardial energetics and ischaemic ventricular fibrillation (VF) in metabolically normal pigs. Domestic farm pigs were treated with metformin (30 mg kg-1 day-1 orally for 2-3 weeks; n = 36) or received no treatment (n = 37). Under anaesthesia, pigs underwent up to 90 min low-flow regional myocardial ischaemia followed by 45 min of reperfusion. Pigs were monitored for arrhythmia, monophasic action potential morphology, haemodynamics and myocardial substrate utilisation, AMP-activated protein kinase (AMPK) phosphorylation activity and ATP concentration. Death due to VF occurred in 12% of pigs treated with metformin compared with 50% of untreated controls (p = 0.03). The anti-fibrillatory effect of metformin was associated with attenuation of action potential shortening in ischaemic myoc...Continue Reading

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Citations

Aug 18, 2017·Cardiovascular Endocrinology·Andrew J Krentz
Jan 15, 2020·Cell and Tissue Research·Simone RennerEckhard Wolf
Sep 29, 2019·International Journal of Molecular Sciences·Andrea BaehrChristian Kupatt
Nov 26, 2020·Cardiovascular Diabetology·Teerapat NantsupawatNipon Chattipakorn
Jul 3, 2021·International Journal of Molecular Sciences·Isabella PanfoliDavide Maggi

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