Faculty Collaboration Database

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

11/23/2005

Pubmed ID

16301224

DOI

10.1213/01.ANE.0000181288.13549.28

Scopus ID

2-s2.0-28344451998 (requires institutional sign-in at Scopus site)   105 Citations

Abstract

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 PS

Author

Dorothee 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, Inhalation
Animals
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