(The FASEB Journal. 2008;22:lb647)
© 2008 FASEB
14,15-Epoxyeicosatrienoic Acid Elicits Pre- and Post-conditioning Protection Against Myocardial Ischemia-Reperfusion Injury In Mice
Atsuko Motoki1,
Matthias Merkel1,
William Packwood2,
Nabil J Alkayed1 and
Donna M Van Winkle1,3
1 Anesthesiology and Peri-Operative Medicine, Oregon Health & Science University, Portland, OR,
2 Research Services,
3 Anesthesiology and Research Services, Veterans Affairs Medical Center, Portland, OR
ABSTRACT
14,15-epoxyeicosatrienic acid (14,15-EET) is a polyunsaturated fatty acid derived from arachidonic acid. It is released during ischemia and rapidly broken down via soluble epoxide hydrolase (sEH). sEH knock out mice have increased ischemic tolerance vs. wild-type. We investigated whether exogenous 14,15-EET elicits cardioprotection when given prior to occlusion (pre-conditioning) or at reperfusion (post-conditioning). We subjected male C57BL\6J mice to 40 min of left coronary artery occlusion and 2 h reperfusion. 14,15-EET or vehicle (25% ethanol) was administered 15 min before occlusion (pre-conditioning group), or 5 min before reperfusion (post-conditioning group). Area-at-risk (AAR) and infarct size (I) were assessed using fluorescent microspheres and triphenyl tetrazolium chloride. Infarct size is expressed as I/AAR (mean±SEM). I/AAR was reduced in the EET pre-conditioning group (24.2±3% n=5 vs. 54.1±3% n=6, p<0.001), and in the post-conditioning group (35.8±1% n=5 vs. 47.7±1% n=5, p<0.01), as compared to vehicle. In summary, 14,15-EET has both pre-conditioning and post-conditioning effects in mouse hearts.
