Adenosine type 1 (A1) receptors mediate protection against myocardial infarction produced by chronic, intermittent ingestion of ethanol in dogs

Background: Chronic consumption of small amounts of ethanol protects myocardium from ischemic injury. We tested the hypothesis that adenosine type 1 (A1) receptors mediate these beneficial effects. Methods: Dogs (n=37) were fed with ethanol (1.5 g/kg) or water mixed with dry food twice per day for 12 weeks, fasted overnight before experimentation, and instrumented for measurement of hemodynamics. Dogs received intravenous drug vehicle (50% polyethylene glycol in 0.1 N sodium hydroxide and 0.9% saline over 15 min) or the selective A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 0.8 mg/kg over 15 min) and were subjected to a 60 min coronary artery occlusion followed by 3 h of reperfusion. Myocardial infarct size and transmural coronary collateral blood flow were measured with triphenyltetrazolium chloride staining and radioactive microspheres, respectively. Results: The area at risk (AAR) for infarction was similar between groups. Pretreatment with ethanol significantly reduced infarct size to 13±2% (n=7) of the AAR as compared to control experiments (26±2%; n=7). DPCPX abolished the protective effects of ethanol pretreatment (30±3%; n=7) but had no effect in dogs that did not receive ethanol (25±2%; n=7). No differences in transmural coronary collateral blood flow were observed between groups. Conclusions: The present findings indicate that chronic ingestion of small amounts of ethanol produces myocardial protection that persists after the discontinuation of ethanol. The results indicate that A1 receptors mediate ethanol-induced preconditioning in dogs independent of alterations in systemic hemodynamics or coronary collateral blood flow.