Inhibition of mitochondrial permeability transition enhances isoflurane-induced cardioprotection during early reperfusion: the role of mitochondrial KATP channels. Anesth Analg 2005 Dec;101(6):1590-1596
Date
11/23/2005Pubmed ID
16301224DOI
10.1213/01.ANE.0000181288.13549.28Scopus ID
2-s2.0-28344451998 (requires institutional sign-in at Scopus site) 105 CitationsAbstract
Inhibition of the mitochondrial permeability transition pore (mPTP) mediates the protective effects of brief, repetitive ischemic episodes during early reperfusion after prolonged coronary artery occlusion. Brief exposure to isoflurane immediately before and during early reperfusion also produces cardioprotection, but whether mPTP is involved in this beneficial effect is unknown. We tested the hypothesis that mPTP mediates isoflurane-induced postconditioning and also examined the role of mitochondrial KATP (mKATP) channels in this process. Rabbits (n = 102) subjected to a 30-min coronary occlusion followed by 3 h reperfusion received 0.9% saline (control), isoflurane (0.5 or 1.0 MAC) administered for 3 min before and 2 min after reperfusion, or the mPTP inhibitor cyclosporin A (CsA, 5 or 10 mg/kg) in the presence or absence of the mPTP opener atractyloside (5 mg/kg) or the selective mK(ATP) channel antagonist 5-hydroxydecanoate (5-HD; 10 mg/kg). Other rabbits received 0.5 MAC isoflurane plus 5 mg/kg CsA in the presence and absence of atractyloside or 5-HD. Isoflurane (1.0 but not 0.5 MAC) and CsA (10 but not 5 mg/kg) reduced (P < 0.05) infarct size (21% +/- 4%, 44% +/- 6%, 24% +/- 3%, and 43% +/- 6%, respectively, mean +/- sd of left ventricular area at risk; triphenyltetrazolium staining) as compared with control (42% +/- 7%). Isoflurane (0.5 MAC) plus CsA (5 mg/kg) was also protective (27% +/- 4%). Neither atractyloside nor 5-HD alone affected infarct size, but these drugs abolished protection by 1.0 MAC isoflurane, 10 mg/kg CsA, and 0.5 MAC isoflurane plus 5 mg/kg CsA. The results indicate that mPTP inhibition enhances, whereas opening abolishes, isoflurane-induced postconditioning. This isoflurane-induced inhibition of mitochondrial permeability transition is dependent on activation of mitochondrial KATP channels in vivo.
Author List
Krolikowski JG, Bienengraeber M, Weihrauch D, Warltier DC, Kersten JR, Pagel PSAuthors
Paul S. Pagel MD, PhD Professor in the Anesthesiology department at Medical College of WisconsinDorothee Weihrauch DVM, PhD Research Scientist II in the Anesthesiology department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
Anesthetics, InhalationAnimals
Ion Channels
Isoflurane
Male
Mitochondrial Membrane Transport Proteins
Myocardial Infarction
Myocardial Reperfusion Injury
Phosphatidylinositol 3-Kinases
Potassium Channels
Proto-Oncogene Proteins c-bcl-2
Rabbits