Late Phases of Cardioprotection During Remote Ischemic Preconditioning and Adenosine Preconditioning Involve Activation of Neurogenic Pathway

BACKGROUND: The role of the neurogenic pathway in early phases of cardioprotection during remote ischemic preconditioning (RIPC) and adenosine preconditioning is reported. AIM: This study was designed to explore the involvement of the neurogenic pathway in late phases of cardioprotection during RIPC and adenosine preconditioning. MATERIAL AND METHODS: Fifty-four Wistar rats were used and divided into 9 experimental groups. RIPC was induced by tying the blood pressure cuff around the hind limb and subjecting to 4 cycles of inflation and deflation of 5 minutes each. In early RIPC, the heart was isolated immediately after the last episode of RIPC, whereas in late RIPC, the heart was isolated 24 hours after the last cycle of RIPC. In a similar way, adenosine preconditioning was instituted in early and late phases by either isolating the heart 40 minutes or 24 hours after adenosine (4 mg/kg, intraperitoneally [i.p.]) administration. Isolated hearts were subjected to ischemia-reperfusion (I/R) injury on the Langendorff's system. RESULTS: Both early and late phases of RIPC and adenosine preconditioning significantly abrogated I/R-induced myocardial injury in terms of decrease in the release of lactate dehydrogenase, creatine kinase, and decrease in infarct size. Pretreatment with hexamethonium, a ganglion blocker (20 mg/kg, i.p.), significantly abolished the cardioprotective effects of both early and late phases of RIPC and adenosine preconditioning. CONCLUSION: Apart from the involvement of the neurogenic pathway in the early phases, there is a critical role of the neurogenic pathway in the late phase of cardioprotection during RIPC and adenosine preconditioning.