Metformin Prevents Myocardial Reperfusion Injury by Activating the Adenosine Receptor

• DOI: 10.1097/fjc.0b013e31819fd4e7
• Publication Date: 2009-05-21T12:57:59Z
• Authors: Marta Paiva; Niels P Riksen; Sean M Davidson; Derek J Hausenloy; Pedro Monteiro; Lino Gonçalves; Luís Providência; Gerard A Rongen; Paul Smits; Mihaela M Mocanu; Derek M Yellon
• Keywords: Cardioprotection; Adenosine A1 receptor; Adenosine receptor antagonist

Metformin improves cardiovascular outcomes in patients with type 2 diabetes compared other glucose-lowering drugs. Experimental studies have shown that metformin can increase the intracellular concentration of adenosine monophosphate, which is a major determinant formation adenosine. We hypothesize metformin, given at reperfusion, limit myocardial infarct size due to increased receptor stimulation. Isolated perfused hearts from Sprague-Dawley rats were subjected 35 minutes regional ischemia and 120 reperfusion. Perfusion (50 μM) for first 15 reperfusion reduced (percent area risk) 42% ± 2% 19% 4% (n ≥ 6; P < 0.01), was blocked by concomitant perfusion antagonist 8-p-sulfophenyltheophylline (100 μM; 43% 3%) or nitrobenzylthioinosine (a blocker transmembranous transport; 1 45% 5%). In addition, intravenous administration (5 mg/kg) rat situ model infarction (34% 6% vs. 62% 5%; completely abolished (61% 3%). conclude reduces infarction, critically dependent on stimulation, probably via