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

Abstract：

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<0.05), CYC A alone or in combination with IbTx or DES also reduced IS (P<0.05). 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. 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.

journal_name

Br J Anaesth

journal_title

British journal of anaesthesia

authors

Stumpner J,Lange M,Beck A,Smul TM,Lotz CA,Kehl F,Roewer N,Redel A

doi

10.1093/bja/aer496

subject

Has Abstract

pub_date

2012-04-01 00:00:00

pages

594-601

issue

eissn

0007-0912

issn

1471-6771

pii

S0007-0912(17)32264-X

journal_volume

108

pub_type

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