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dc.contributor.authorPeart, Jasonen_US
dc.contributor.authorHeadrick, Johnen_US
dc.contributor.authorJ. Gross, Garretten_US
dc.contributor.editorDr. R. A. Walsh (Editor-in-Chief)en_US
dc.description.abstractChronic opioid preconditioning confers a pronounced and prolonged cardioprotective phenotype, existing at least 24 hours beyond opioid drug withdrawal. This study aims to delineate both the trigger and mediation phase of this cardioprotective state. To this end, we employed an isolated, perfused murine heart model of ischemia reperfusion. Following 25 min ischemia and 45 min reperfusion, placebo-treated hearts exhibited a pronounced degree of contractile dysfunction (EDP, 32 ᠳ mmHg; RPP, 40 ᠴ% baseline). In stark contrast, chronic morphine-treated (CMP) hearts (75 mg pellet, 5 days) displayed a significant recovery of RPP (83 ᠳ%) and an almost complete return of EDP. As expected, co-administration of opioid antagonist, naloxone, via osmotic minipump for 5 days prevented the initiation ("trigger" phase), and thus, protection of CMP (RPP, 46 ᠲ%). Moreover, 5 day infusion of the primary morphine metabolites, morphine-3-glucuronide and morphine-6-glucuronide, failed to induced any form of cardioprotection, suggesting that neither the mu-opioid receptor nor metabolites are involved. Concurrent infusion of the PKA inhibitor, PKI, during the activation phase failed to abolish the CMP-mediated protection (69 ᠵ% RPP). Interestingly, naloxone, administered pre-and post-ischemia (the "mediation" phase), following 5 days of morphine exposure, failed to modify the CMP-induced phenotype, while PKI completely abolished CMP protection, with no effect on placebo-treated hearts. These data offer an insight into the genesis of CMP in the murine heart, whereby the trigger phase is opioid receptor-dependent and PKA-independent, whereas the mediation phase is independent of opioid receptor activation and is PKA-dependent.en_US
dc.publisherAcademic Pressen_US
dc.publisher.placeUnited Kingdomen_US
dc.relation.ispartofjournalJournal of Molecular and Cellular Cardiologyen_US
dc.subject.fieldofresearchCardiology (incl. Cardiovascular Diseases)en_US
dc.titleTrigger and mediation phase of chronic opioid preconditioning are mediated via divergent pathwaysen_US
dc.typeJournal articleen_US
dc.type.descriptionC3 - Letter or Noteen_US
dc.type.codeC - Journal Articlesen_US
gro.facultyGriffith Health, School of Medical Scienceen_US
gro.hasfulltextNo Full Text

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