Pretreatment Attenuates Myocardial Ischemia-Reperfusion Injury via mitoBK.

extracts (EGb) alleviate myocardial ischemia/reperfusion (MI/R) injury. However, the underlying mechanisms have not yet been characterized. This study aimed to investigate whether activation of large-conductance -activated channels at the inner mitochondrial membrane ( of cardiomyocytes is involved in extract-mediated cardioprotection. Shuxuening injection (SXNI, 12.5ml/kg/d), a widely prescribed herbal medicine containing extracts in China, or vehicle, was administered to C57BL/6 mice via tail vein injection for one week prior to surgical procedures. The mitoBK blocker paxilline (PAX) (1ml/kg, 115 nM) was administered via tail vein injection 30min prior to the onset of ischemia. The mice were randomly divided into the following groups: Sham, MI/R, MI/R+SXNI, and MI/R+SXNI+PAX. MI/R was induced by ligating the left anterior descending coronary artery for 30min with subsequent reperfusion for 24h. SXNI pretreatment conferred cardioprotective effects against MI/R injury as evidenced by reduced infarct size, improved cardiac function, and improved mitochondrial function. However, these effects were abrogated by co-administration with PAX. In addition, activation of mitoBK by extract EGb761 reduced hypoxia/reoxygenation (H/R)-induced cardiomyocyte injury through the inhibition of mitochondrial fragmentation, restoration of the mitochondrial membrane potential, decreased generation of superoxide, and inhibition of apoptosis which is associated with alleviating mitochondrial overload. These results indicated that extracts pretreatment protected against MI/R injury via activation of mitoBK.