Puneet Kaur Randhawa
Punjabi University, India
Biography
Abstract
Introduction: Remote ischemic preconditioning (RIPC) is the phenomenon that harnesses the body’s endogenous protective mechanisms against prolonged ischemia-reperfusion-induced injury.
Aim & Objective: The present study aims to explore the involvement of glycogen synthase kinase-3β and gap junction signaling in TRPV1 and remote hind preconditioning-induced cardioprotection.
Materials & Methods: In the present study, four consecutive cycles (5 minutes of ischemia-reperfusion) of remote hind limb preconditioning stimulus were delivered using a blood pressure cuff fastened at the inguinal level of the rat. The isolated rat hearts were mounted on the Langendorff’s apparatus and were exposed to 30 minutes of global ischemia-120 minutes of reperfusion. Sustained ischemia-reperfusion led to cardiac injury that was assessed in terms of infarct size, LDH release, CK release, LVDP, +dp/dtmax, -dp/dtmin, heart rate and coronary flow rate. The pharmacological agents employed in the present study included capsaicin (10 mg kg-1) as TRPV1 channel activator, AR-A014418 (1 and 3 mg kg-1) as glycogen synthase kinase-3β inhibitor and carbenoxolone disodium (50 and 100 mg kg-1) as gap junction blocker.
Results & Conclusion: Remote hind limb, capsaicin and AR-A014418 preconditioning led to significant reduction in the infarct size, LDH release, CK release and improved LVDP, +dp/dtmax, -dp/dtmin, heart rate and coronary flow rate. However, remote hind limb, capsaicin and AR-A014418 preconditioning-induced cardioprotective effects were remarkably reduced in the presence of carbenoxolone (100 mg kg-1). This indicates that remote preconditioning stimulus probably activates TRPV1 channels that may inhibit glycogen synthase kinase-3β activity which subsequently enhances gap junction coupling to produce cardioprotective effects.