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

Abstract

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.

Hydrogen sulfide restores cardioprotective effects of remote ischemic preconditioning in aged rats via HIF-1α/Nrf2 signaling pathway

“…an early phase (first window) and late phase (second window) [3,35]. These observations of the present study documenting the myocardial injury in response to ischemia and reperfusion along with the cardioprotective effects of the late phase of remote preconditioning are in accordance with the previously published studies [4,36]. Moreover, the present study results document that the cardioprotective effects of the late phase of remote preconditioning were significantly attenuated in old rats.…”

“…Hydrogen sulfide restores cardioprotective effects of remote ischemic preconditioning in aged rats via HIF-1/Nrf2 signaling pathway that the late phase of remote preconditioning confers a higher magnitude of cardioprotection than the early phase [3,4].…”

Liraglutide restores late cardioprotective effects of remote preconditioning in diabetic rats via activation of hydrogen sulfide and nuclear factor erythroid 2-related factor 2 signaling pathway

“…Such four alternate cycles of ischemia and reperfusion to the hind limb constituted remote preconditioning. After 24 h, the rats were sacrificed to isolate hearts, which were perfused on the Langendorff apparatus 3 .…”

“…Apart from short term effects of diabetes, long-standing uncontrolled hyperglycemia in diabetes produces a number of complications, including increase in the tendency to develop ischemia-reperfusion induced myocardial injury 1,2 . Remote preconditioning a therapeutic strategy in which short episodes of ischemia and reperfusion to an organ other than heart (nontarget or remote organ) confers protection to heart from sustained ischemia-reperfusion injury 3 . This therapeutic strategy has been used in preclinical as well in clinical setup to confer protection to heart against ischemiareperfusion injury 4,5 .…”

Protective Effects of Ischemic Postconditioning on Livers in Rats with Limb Ischemia-Reperfusion via Glycogen Synthase Kinase 3 beta (GSK-3β)/Fyn/Nuclear Receptor-Erythroid-2-Related Factor (Nrf2) Pathway

“…Murry et al [ 16 ] put forward the concept of ischemic preconditioning (IPC) in 1986, which suggests that the short-term reperfusion of ischemic myocardium can significantly improve myocardial I/R injury. Many studies have shown that IPC can be used to alleviate I/R injury of various tissues and organs in many animals [ 17 – 19 ]. However, the clinical value of IPC is limited because it is difficult to estimate the time of ischemia of tissues and organs in clinical practice.…”