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Abstract
Landiolol, a highly cardioselective β1-blocker, has cardioprotective effects against ischemia-reperfusion injury, although the precise mechanism is still unclear. The aim of this study was to clarify the cardioprotective mechanism of landiolol. Experiments were performed on Langendorff-perfused rat hearts undergoing 20 min stabilization, and 45 min of ischemia followed by 60 min of reperfusion. Various drugs with or without landiolol (100 μM) were administered before ischemia for 20 min. Preischemic administration of landiolol reduced cardiac cellular damage and improved the recovery of cardiac function by about 40%. The α1 blocker prazosin, the protein kinase C (PKC) inhibitor chelerythrine or the KATP channel blocker glibenclamide, but not the selective mitochondrial KATP channel blocker 5-hydroxydecanoate abrogated the cardioprotective effect induced by landiolol. Following landiolol pretreatment the activation of PKCε and heat shock protein 27 were significantly higher than that in control. These data indicate that preischemic application of landiolol induces cardioprotective effects through PKCε-mediated pathway, similar to that afforded by ischemic preconditioning.