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Evidence for role of epoxyeicosatrienoic acids in mediating ischemic preconditioning and postconditioning in dog. Am J Physiol Heart Circ Physiol 2009 Jul;297(1):H47-52 PMID: 19448143 PMCID: PMC2711741

Pubmed ID

19448143

DOI

10.1152/ajpheart.01084.2008

Abstract

Cytochrome P-450 (CYP) epoxygenases and their arachidonic acid (AA) metabolites, the epoxyeicosatrienoic acids (EETs), have been shown to produce marked reductions in infarct size (IS) in canine myocardium either given before an ischemic insult or at reperfusion similar to that produced in ischemic preconditioning (IPC) and postconditioning (POC) protocols. However, no studies have addressed the possibility that EETs serve a beneficial role in IPC or POC. We tested the hypothesis that EETs may play a role in these two phenomena by preconditioning dog hearts with one 5-min period of total coronary occlusion followed by 10 min of reperfusion before 60 min of occlusion and 3 h of reperfusion or by postconditioning with three 30-s periods of reperfusion interspersed with three 30-s periods of occlusion. To test for a role of EETs in IPC and POC, the selective EET antagonists 14,15-epoxyeicosa-5(Z)-enoic acid (14,15-EEZE) or its derivative, 14,15-epoxyeicosa-5(Z)-enoic acid 2-[2-(3-hydroxy-propoxy)-ethoxy]-ethyl ester (14,15-EEZE-PEG), were administered 10 min before IPC, 5 min after IPC, or 5 min before POC. In a separate series, the selective EET synthesis inhibitor N-methylsulfonyl-6-(propargyloxyphenyl)hexanamide (MS-PPOH) was administered 10 min before IPC. Infarct size was determined by tetrazolium staining and coronary collateral blood flow at 30 min of occlusion and reperfusion flow at 3 h by radioactive microspheres. Both IPC and POC produced nearly equivalent reductions in IS expressed as a percentage of the area at risk (AAR) [Control 21.2 +/- 1.2%, IPC 8.3 +/- 2.2%, POC 10.1 +/- 1.8% (P < 0.001)]. 14,15-EEZE, 14,15-EEZE-PEG, and MS-PPOH markedly attenuated the cardioprotective effects of IPC and POC (14,15-EEZE and 14,15-EEZE-PEG) at doses that had no effect on IS/AAR when given alone. These results suggest a unique role for endogenous EETs in both IPC and POC.

Author List

Gross GJ, Gauthier KM, Moore J, Campbell WB, Falck JR, Nithipatikom K

Author

William B. Campbell PhD Chair, Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin




Scopus

2-s2.0-67650095389   35 Citations

MESH terms used to index this publication - Major topics in bold

8,11,14-Eicosatrienoic Acid
Amides
Animals
Blood Pressure
Coronary Circulation
Dogs
Eicosanoids
Female
Heart
Heart Rate
Ischemic Preconditioning, Myocardial
Male
Myocardial Infarction
Myocardium
jenkins-FCD Prod-353 9ccd8489072cb19f5b9f808bb23ed672c582f41e