Stretch-induced protection shares a common mechanism with ischemic preconditioning in rabbit heart

Abstract

We sought to determine whether stretch-induced preconditioning may be related to activation of adenosine receptors, ATP-sensitive K+ (K+ATP) channels, and/or protein kinase C (PKC) in the rabbit heart. Anesthetized rabbits underwent 30 min of coronary artery occlusion followed by 3 h of reperfusion. Ischemic preconditioning was induced by one episode of 5 min of ischemia followed by 5 min of reperfusion, and stretch preconditioning was induced by a transient volume overload. The abilities of gadolinium (Gd3+), a blocker of stretch-activated channels, glibenclamide (Glib), a blocker of K+ATP channels, 8-(p-sulfophenyl)-theophylline (8-SPT), a blocker of adenosine receptors, and polymyxin B (PMXB), an antagonist of PKC, to prevent the infarct size-limiting effect of stretch-induced preconditioning were evaluated. Because the infarct size-reducing effect of stretch occurred in the absence of ischemia and was prevented by previous administration of Gd3+, Glib, 8-SPT, and PMXB, we propose that activation of mechanosensitive ion channels protects the rabbit heart from subsequent sustained ischemic insult, likely through a mechanism that involves downstream activation of PKC, adenosine receptors, and/or K+ATP channels.