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dc.contributor.authorR. Gross, Ericen_US
dc.contributor.authorN. Peart, Jasonen_US
dc.contributor.authorK. Hsu, Annaen_US
dc.contributor.authorA. Auchampach, Johnen_US
dc.contributor.authorJ. Gross, Garretten_US
dc.description.abstractSelective d-opioid agonists produce delayed cardioprotection that lasts for 24-48 h in rats; however, the maximum length of the cardioprotective window is unclear. In this study, we attempted to prolong the cardioprotective window using a unique d-opioid agonist, fentanyl isothiocyanate (FIT), which binds irreversibly to the -receptor, and determined the role of the phosphatidylinositol 3-kinase (PI3K) pathway as a trigger or end effector of FIT-induced cardioprotection. Initially, male rats were administered FIT (10 姯kg) 10 min before hearts were subjected to 30 min of ischemia and 2 h of reperfusion followed by infarct size (IS) assessment. Acute FIT administration reduced IS when given before ischemia, 5 min before reperfusion, or 10 s after reperfusion compared with control. IS reduction also occurred following a single dose of FIT at 48, 72, 96, and 120 h after administration vs. control, with the maximum effect observed at 96 h. FIT-induced IS reduction at 96 h was completely abolished when the irreversible PI3K inhibitor wortmannin (15 姯kg) was given before FIT during the trigger phase; however, the effect was only partially abrogated when wortmannin was given 96 h later. These data suggest that FIT has a prolonged cardioprotective window greater than that of any previously described cardioprotective agent that requires PI3K primarily in the trigger phase but also partially, as a mediator or end effectoren_US
dc.publisherAmerican Physiological Societyen_US
dc.publisher.placeUnited Statesen_US
dc.relation.ispartofjournalAmerican Journal of Physiology: Heart and Circulatory Physiologyen_US
dc.titleExtending the cardioprotective window using a novel δ-opioid agonist fentanyl isothiocyanate via the PI3-kinase pathwayen_US
dc.typeJournal articleen_US
dc.type.descriptionC1 - Peer Reviewed (HERDC)en_US
dc.type.codeC - Journal Articlesen_US
gro.rights.copyrightSelf-archiving of the author-manuscript version is not yet supported by this journal. Please refer to the journal link for access to the definitive, published version or contact the author[s] for more information.en_US
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