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<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.
Department of Anaesthesia and Critical Care, University of Wuerzburg, Oberduerrbacher Str. 6, 97080 Wuerzburg, Germany. stumpner_j@klinik.uni-wuerzburg.de
J
J
Stumpner
M
M
Lange
A
A
Beck
T M
TM
Smul
C A
CA
Lotz
F
F
Kehl
N
N
Roewer
A
A
Redel
D000704:Analysis of Variance; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D000077335:Desflurane; D004195:Disease Models, Animal; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods; D007530:Isoflurane / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism*; D000083162:Mitochondrial Permeability Transition Pore; D009203:Myocardial Infarction / Q000378:metabolism* / Q000517:prevention & control*; D024681:Potassium Channels, Calcium-Activated / Q000378:metabolism*
D018685:Anesthetics, Inhalation; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D024681:Potassium Channels, Calcium-Activated; D000077335:Desflurane; D007530:Isoflurane