ALCOHOL-CONSUMPTION REDUCES ISCHEMIA-REPERFUSION INJURY BY SPECIES-SPECIFIC SIGNALING IN GUINEA-PIGS AND RATS

We recently discovered that regular alcohol consumption reduces ischem ia-reperfusion injury to the same degree as ischemic preconditioning i n guinea pig hearts. Ischemic preconditioning, like this cardioprotect ive effect of alcohol, is mediated by adenosine signaling in guinea pi gs. In rats, ischemic preconditioning may be mediated predominantly by al-adrenergic signaling. To be certain that this protective effect of alcohol is a general biological response, we searched for alcohol's c ardioprotection in rat and identified a potential signaling mechanism. Hearts isolated from alcohol-fed guinea pigs and rats were subjected to ischemia-reperfusion. Hearts from alcohol-fed animals showed greate r recovery of left ventricular developed pressure than controls (guine a pigs, 46 vs. 29%; rats, 50 vs. 31%) and decreased myocyte necrosis a ssessed by creatine kinase release (guinea pigs, 204 +/- 42 vs. 440 +/ - 70 U . ml(-1) . g dry wt(-1); rats 158 +/- 13 vs. 328 +/- 31 U . ml( -1) . g dry wt(-1)). Adenosine receptor blockade [8-(p-sulfophenyl)the ophylline] abolished alcohol's protection in guinea pig but not rat he arts. By contrast, alpha(1)-adrenergic blockade (prazosin) abolished a lcohol's protection in rat but not guinea pig hearts. We conclude that regular alcohol consumption reduces ischemia-reperfusion injury and i s mediated by species-specific signaling mechanisms. A major goal of c ardiovascular research is to find a pharmacologically induced chronic state of preconditioning. Understanding the mechanisms of alcohol's ca rdioprotection against ischemia-reperfusion injury may aid in reaching this goal.