Adenosine Type 1 (A ) Receptors Mediate Protection Against Myocardial 1 Infarction Produced by Chronic, Intermittent Ingestion of Ethanol in Dogs
Format of Original
International Journal of Cardiology
Original Item ID
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.
Kehl, Franz; Krolikowski, John G.; LaDisa, John F.; Kersten, Judy R.; Warltier, David C.; and Pagel, Paul S., "Adenosine Type 1 (A ) Receptors Mediate Protection Against Myocardial 1 Infarction Produced by Chronic, Intermittent Ingestion of Ethanol in Dogs" (2003). Biomedical Engineering Faculty Research and Publications. 223.