Abstract
Desflurane (DES)-induced preconditioning is mediated by large-conductance calcium-activated potassium channels (BKCa). Whether BKCa are involved in anaesthetic-induced post-conditioning is unknown. We tested the hypothesis that DES-induced post-conditioning is mediated by BKCa upstream of the mitochondrial permeability transition pore (mPTP). Pentobarbital-anaesthetized male C57Black/6 mice were ...
Abstract
Desflurane (DES)-induced preconditioning is mediated by large-conductance calcium-activated potassium channels (BKCa). Whether BKCa are involved in anaesthetic-induced post-conditioning is unknown. We tested the hypothesis that DES-induced post-conditioning is mediated by BKCa upstream of the mitochondrial permeability transition pore (mPTP). 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 l 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 BKCa activator NS1619 (1 g g(1)), the BKCa inhibitor iberiotoxin (IbTx, 0.05 g g(1)), the mPTP opener atractyloside (ATRA, 25 g g(1)), and the mPTP inhibitor cyclosporine A (CYC A, 10 g g(1)). Infarct size (IS) was determined with triphenyltetrazolium chloride and the area at risk with Evans Blue, respectively. 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 (P0.05), CYC A alone or in combination with IbTx or DES also reduced IS (P0.05). DES-induced reduction of myocardial IS was completely abolished by IbTx and was partially blocked by ATRA and ATRA partially blocked IS reduction by NS1619. These data suggest that DES-induced post-conditioning against myocardial infarction is mediated by BKCa and mPTP. Cardioprotection by BKCa activator NS1619 might occur, at least in part, independently of mPTP.
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