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1 Department of Anesthesiology, Oregon Health and Sciences University, Portland, OR, USA
2 Department of Research, VA Medical Center, Portland, OR, USA
3 Department of Anesthesiology and Resuscitology, Ehime University Medical School, Matsuyama, Ehime, Japan
4 Department of Anesthesiology, Oregon Health and Sciences University, Portland, OR, USA; Department of Research, VA Medical Center, Portland, OR, USA; Department of Anesthesiology Services, VA Medical Center, Portland, OR, USA
* To whom correspondence should be addressed. E-mail: Donna.Vanwinkle{at}med.va.gov.
Objective. The opioid antagonist naloxone abolishes infarct limitation by myocardial ischemic preconditioning, suggesting that one or more endogenous opioid peptides can mediate cardiac protection against ischemic damage. We tested the hypothesis that the naturally occurring opioid peptide Met5-enkephalin (ME) modulates myocardial infarct size in vivo. Methods. Experiments were conducted in barbiturate-anesthetized open-chest rabbits subjected to regional myocardial ischemia-reperfusion. ME was administered via osmotic mini-pump for 24 hr. Infarct size was assessed with tetrazolium, and is expressed as a percentage of the area-at-risk. Results. Exogenous ME reduced the amount of the risk zone infarcted by ~60% as compared to saline-treated controls. ME-induced protection was sensitive to opioid receptor blockade with naloxone (NAL 50 ± 2% vs. ME+NAL 39 ± 3%, p=ns), and also to blockade of sarcolemmal and mitochondrial KATP channels (5HD 33 ± 3% vs. ME+5HD 43 ± 8%, p=ns; and HMR 1098 60 ± 3% vs. ME+HMR 1098 54 ± 7%, p=ns). Conclusion. We conclude that ME limits ischemic injury in vivo by an opioid-receptor-mediated mechanism that involves both sarcolemmal and mitochondrial KATP channels.
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