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  • Title: Phenylephrine induces early and late cardioprotection through mitochondrial permeability transition pore in the isolated rat heart.
    Author: Naderi R, Imani A, Faghihi M, Moghimian M.
    Journal: J Surg Res; 2010 Nov; 164(1):e37-42. PubMed ID: 20850771.
    Abstract:
    BACKGROUND: The aim of this study was to investigate the role of mitochondrial permeability transition pore (mPTP) in cardioprotection afforded by phenylephrine pretreatment in early and late phases. METHODS: Rat hearts were isolated and perfused with Krebs buffer in Langendorff preparation and subjected to 30 min regional ischemia followed by 60 min of reperfusion. Phenylephrine as a selective α1-adrenoceptor agonist and atractyloside as a specific opener of the mPTP were used. Seven groups (n = 6) of rats were randomly studied: (I) control: surgical procedure was performed with no ischemia/reperfusion, (II) ischemia/reperfusion: hearts underwent regional ischemia/reperfusion, (III) early phenylephrine: phenylephrine (50 μM) was perfused for 5 min prior to ischemia/reperfusion, (IV) late phenylephrine: rats were treated with phenylephrine (10 mg/kg, i.p) 24 h prior to ischemia/reperfusion, (V) early phenylephrine+atractyloside: hearts were perfused with phenylephrine as in group III and then atractyloside (20 mM) 5 min before reperfusion for 20 min, (VI) late phenylephrine+atractyloside: hearts were treated with phenylephrine as in group IV and then received atractyloside (20 mM), 5 min before reperfusion for 20 min, (VII) atractyloside-IR group: hearts were perfused with atractyloside (20 mM) 5 min before reperfusion for 20 min. RESULTS: Compared with ischemia/reperfusion group, perfusion of phenylephrine in early and late phases decreased myocardial infarct size (% of ischemia zone), reduced creatine kinase-MB (CK-MB) in the coronary effluent, and improved cardiac function. Administration of atractyloside abolished cardioprotective effects of phenylephrine in both early and late phases and returned infarct size, CK-MB and cardiac function to levels as seen in ischemia/reperfusion group. CONCLUSION: These results suggest that administration of atractyloside as a specific opener of the mPTP abolishes phenylephrine-induced early and late cardioprotection in the isolated rat hearts.
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