Desflurane-induced post-conditioning against myocardial infarction is mediated by calcium-activated potassium channels: role of the mitochondrial permeability transition pore

Background Desflurane (DES)-induced preconditioning is mediated by large-conductance calcium-activated potassium channels (BK Ca ). Whether BK Ca are involved in anaesthetic-induced post-conditioning is unknown. We tested the hypothesis that DES-induced post-conditioning is mediated by BK Ca upstream of the mitochondrial permeability transition pore (mPTP). Methods Pentobarbital-anaesthetized male C57Black/6 mice were subjected to 45 min coronary artery occlusion (CAO) and 3 h reperfusion. Animals received either no intervention or dimethylsulphoxide (DMSO, 10 µl g –1 ). DES (1.0 MAC, 7.5 vol%) was administered for 18 min, starting 3 min before the end of CAO. The following agents were given either alone or in combination with DES: the BK Ca activator NS1619 (1 µg g −1 ), the BK Ca inhibitor iberiotoxin (IbTx, 0.05 µg g −1 ), the mPTP opener atractyloside (ATRA, 25 µg g −1 ), and the mPTP inhibitor cyclosporine A (CYC A, 10 µg g −1 ). Infarct size (IS) was determined with triphenyltetrazolium chloride and the area at risk with Evans Blue, respectively. Results IS in control animals was 48(6)%. Neither DMSO, IbTx nor ATRA affected myocardial IS. DES alone or NS1619 alone or the combination reduced IS ( P P Conclusions These data suggest that DES-induced post-conditioning against myocardial infarction is mediated by BK Ca and mPTP. Cardioprotection by BK Ca activator NS1619 might occur, at least in part, independently of mPTP.