Remote ischemic preconditioning-induced late cardioprotection: possible role of melatonin-mitoKATP-H2S signaling pathway

Purpose: Remote ischemic preconditioning (RIPC) confers cardioprotection against ischemia reperfusion (IR) injury. However, the precise mechanisms involved in RIPC-induced cardioprotection are not fully explored. The present study was aimed to identify the role of melatonin in RIPC-induced late cardioprotective effects in rats and to explore the role of H2 S, TNF-α and mitoKATP in melatoninmediated effects in RIPC. Methods: Wistar rats were subjected to RIPC in which hind limb was subjected to four alternate cycles of ischemia and reperfusion of 5 min duration by using a neonatal blood pressure cuff. After 24 h of RIPC or ramelteon-induced pharmacological preconditioning, hearts were isolated and subjected to IR injury on the Langendorff apparatus. Results: RIPC and ramelteon preconditioning protected the hearts from IR injury and it was assessed by a decrease in LDH-1, cTnT and increase in left ventricular developed pressure (LVDP). RIPC increased the melatonin levels (in plasma), H2 S (in heart) and decreased TNF-α levels. The effects of RIPC were abolished in the presence of melatonin receptor blocker (luzindole), ganglionic blocker (hexamethonium) and mitochondrial KATP blocker (5-hydroxydecanoic acid). Conclusion: RIPC produce delayed cardioprotection against IR injury through the activation of neuronal pathway, which may increase the plasma melatonin levels to activate the cardioprotective signaling pathway involving the opening of mitochondrial KATP channels, decrease in TNF-α production and increase in H2 S levels. Ramelteon-induced pharmacological preconditioning may also activate the cardioprotective signaling pathway involving the opening of mitochondrial KATP channels, decrease in TNF-α production and increase in H2 S levels.

Effect of terminalia arjuna on isoproterenol induced myocardial infarction.

Terminalia arjuna has been reported as a cardio tonic in the ancient literature. Its bark is used in many commercial formulations. Its effect on isoproterenol induced myocardial infarction has been studied. Treatment of albino rats with T. arjuna bark showed a marked cardio protective effect. The administration of isoproterenol significantly increased the levels of SGOT, SGPT, CPK and alkaline phosphatase. T. arjuna treatment prevented the elevation of the activities of these enzymes. Further, the treatment with T. arjuna alone caused a marked decrease in the basal activities of SGOT, SGPT and alkaline phosphatase, bringing them below the normal levels, present in control animals. It also affected the serum HDL and triglyceride levels overcoming the adverse effect of isoproterenol on these parameters. These effects were further substantiated by the histopathological studies of cardiac tissues. These data suggest that T. arjuna can be used as a general cardio tonic and can be beneficial in the prevention and treatment of heart ailments