J Mol Cell Cardiol 33, 2015–2022 (2001) doi:10.1006/jmcc.2001.1465, available online at http://www.idealibrary.com on Acute Alcohol-induced Protection against Infarction in Rabbit Hearts: Differences from and Similarities to Ischemic Preconditioning Maike Krenz 1 , Christopher P. Baines 1 , Gerd Heusch 1,3 , James M. Downey 1 and Michael V. Cohen 1,2 Departments of 1 Physiology and 2 Medicine, University of South Alabama, Mobile, AL, USA and 3 Department of Pathophysiology, University of Essen Medical School, Essen, Germany (Received 22 May 2001, accepted 23 August 2001) M. K, C. P. B, G. H, J. M. D  M. V. C. Acute Alcohol-induced Protection against Infarction in Rabbit Hearts: Differences from and Similarities to Ischemic Preconditioning. Journal of Molecular and Cellular Cardiology (2001) 33, 2015–2022. Recent studies reveal that brief ethanol exposure induces cardioprotection against simulated ischemia in cardiomyocytes by the activation of protein kinase C-. The present study tests the ability of ethanol to induce protection in rabbit hearts in which infarct size was the end-point and explores the signal transduction pathways involved. In isolated rabbit hearts, 50 m ethanol infused for 5 min with 10 min of washout prior to 30 min of regional ischemia reduced infarct size (triphenyltetrazolium chloride staining) by 49%. Neither adenosine receptor blockade with 8-(p-sulfophenyl) theophylline nor the free radical scavenger N-2-mercaptopropionyl glycine inhibited the protection triggered by ethanol. In contrast, protein kinase C inhibition with chelerythrine, protein tyrosine kinase inhibition with genistein, and blockade of ATP-sensitive potassium channels (K ATP ) with either 5-hydroxydecanoate or glibenclamide did abolish protection. Thus, transient ethanol exposure followed by washout prior to ischemia elicits a preconditioning-like effect involving protein kinase C, at least one protein tyrosine kinase, and K ATP channels, but neither adenosine nor free radicals.  2001 Academic Press K W: Ethanol; Ischemic preconditioning; Protein kinase C; Signal transduction. was also protective, as assessed by creatine kinase Introduction release during reperfusion. The protection induced by ethanol in rat cardiomyocytes could be blocked Acute ethanol exposure was recently reported to protect isolated rat cardiomyocytes and isolated rat by the protein kinase C inhibitor chelerythrine and by an  isoform-specific peptide inhibitor of protein hearts. 1 Cardiomyocytes were exposed to 10–50 m ethanol either with or without washout and then kinase C. These characteristics resemble those of ischemic preconditioning (IPC). Isoform-selective subjected to simulated ischemia by spinning them into a pellet and covering them with microballoons translocation and activation of PKC is thought to be a critical step in the signaling pathway of both to exclude oxygen. Ethanol exposure with and with- out washout significantly decreased osmotic fra- classical 2 and delayed 3 IPC in rabbits. However, it is not known whether cardioprotection induced by gility in this model. In isolated rat hearts, exposure to 10 m ethanol before and throughout ischemia ethanol is the result of the same signaling cascade Please address all correspondence to: Michael V. Cohen, MD, Department of Physiology, MSB3050, University of South Alabama, College of Medicine, Mobile, AL 36688, USA. E-mail: mcohen@usamail.usouthal.edu 0022–2828/01/112015+08 $35.00/0  2001 Academic Press