Effects of metformin on atrial and ventricular arrhythmias: evidence from cell to patient

Table 4 Effects of metformin on ventricular arrhythmias: reports from in vivo studies

Model	Metformin (dose/ duration)	Key results and major findings								Interpretation	References
Model	Metformin (dose/ duration)	Energy homeostasis	Oxidative stress	Intra-cellular Ca	LV dP/dt	Infarct/ apoptosis	EP changes	p-Cx 43	VT/ VF	Interpretation	References
Domestic farm pigs with cardiac I/R injury -I(50% flow)/R = 90/45 min	-Chronic metformin 30 mg/kg/day per oral for 2–3 weeks)	- ↑↑AMPK - ↑CS - ↑ATP - <-> O₂, glucose use, lactate	–	–	<->	–	-↓MAP shortening -↓APD dispersion	–	↓	Chronic metformin treatment reduced ischemic VF by preventing MAP shortening and repolarization heterogeneity via AMPK activation, leading to preserved myocardial ATP	[88]
	-Acute Metformin IV 100 mg/kg	<-> AMPK	–	–	<->	–	<->	–	<->		[88]
Male Wistar rats fed with high fat for 12 weeks underwent cardiac I/R injury. (LAD ligation 30/R 120 min)	Metformin 30 mg/kg/day for 3 weeks	↑Mito-chondrial function	↓MDA	-↓Diastolic Ca -↑transient amp/decay	↑	↓Infarct/ ↓Bax, ↑Bcl-2	↑HRV	<->	<->	Metformin alone did not reduce VT/VF incidence. However, combined drugs effectively decreased VT/VF via increased p-Cx43	[63]
	Metformin+ Vildagliptin	↑Mito-chondrial function	↓MDA	-↓Diastolic Ca -↑Transient amp/decay	↑	↓Infarct/ ↓Bax, ↑Bcl-2	↑HRV	↑	↓		[63]

AMPK 5' adenosine monophosphate-activated protein kinase, APD action potential duration, ATP adenosine triphosphate, Ca calcium, CS citrate synthase, EP electrophysiologic, HRV heart rate variability, I/R ischemic/reperfusion, LAD left anterior descending coronary artery, LV left ventricular, MAP monophasic action potential, MDA malondialdehyde, pAMPK phosphorylated 5' adenosine monophosphate-activated protein kinase, p-Cx phosphorylated Connexin, VT/VF ventricular tachycardia/ventricular fibrillation

ISSN: 1475-2840