Phenylephrine produces late pharmacological preconditioning in the isolated rat heart.

We assume that phenylephrine produces late pharmacological preconditioning through the opening of the mitochondrial KATP channels. To test this hypothesis, rat hearts were isolated and perfused with Krebs buffer solution by Langendorff method and subjected to 30 min regional ischemia followed by 60 min of reperfusion. In this study, phenylephrine as a selective alpha1-adrenoceptor agonist and 5HD (5-hydroxydecanoate) as a putatively specific blocker of the mitochondrial KATP channels were used. Rats were randomly divided into six groups (n=6): (I) Control: surgical procedure was performed with no ischemia/reperfusion, (II) ischemia/reperfusion: hearts underwent regional ischemia/reperfusion, (III) phenylephrine-early preconditioning: phenylephrine (50 microM) was perfused for 5 min prior to ischemia/reperfusion, (IV) phenylephrine-late preconditioning: rats were treated with phenylephrine (10 mg/kg, i.p) 24h prior to ischemia/reperfusion, (V) 5HD-phenylephrine early preconditioning-: 5HD (100 microM) was perfused for 5 min prior to phenylephrine as seen in group III, (VI) Phenylephrine late preconditioning-5HD: 5HD (100 microM) was perfused for 5 min prior to ischemia/reperfusion as seen in group IV and (VII) 5HD- ischemia/reperfusion: 5HD (100 microM) was perfused for 5 min prior to ischemia/reperfusion. Compared to ischemia/reperfusion group, phenylephrine in early and late phases decreased myocardial infarct size (% of ischemia zone), reduced CK-MB (Creatine Kinase-MB) release in the coronary effluent and improved cardiac function. Pretreatment with 5HD abolished phenylephrine-induced cardioprotection in early and late phases. It is concluded that phenylephrine-induced late cardioprotection was abolished by administration of 5HD in the isolated rat hearts.