Mitochondrial adenosine triphosphate-regulated potassium channel opening acts as a trigger for isoflurane-induced preconditioning by generating reactive oxygen species. Anesthesiology 2003 Apr;98(4):935-43
Date
03/27/2003Pubmed ID
12657856DOI
10.1097/00000542-200304000-00021Scopus ID
2-s2.0-0344211929 (requires institutional sign-in at Scopus site) 116 CitationsAbstract
BACKGROUND: Whether the opening of mitochondrial adenosine triphosphate-regulated potassium (K(ATP)) channels is a trigger or an end effector of anesthetic-induced preconditioning is unknown. We tested the hypothesis that the opening of mitochondrial K(ATP) channels triggers isoflurane-induced preconditioning by generating reactive oxygen species (ROS) in vivo.
METHODS: Pentobarbital-anesthetized rabbits were subjected to a 30-min coronary artery occlusion followed by 3 h reperfusion. Rabbits were randomly assigned to receive a vehicle (0.9% saline) or the selective mitochondrial K(ATP) channel blocker 5-hydroxydecanoate (5-HD) alone 10 min before or immediately after a 30-min exposure to 1.0 minimum alveolar concentration (MAC) isoflurane. In another series of experiments, the fluorescent probe dihydroethidium was used to assess superoxide anion production during administration of 5-HD or the ROS scavengers N-acetylcysteine or N-2-mercaptopropionyl glycine (2-MPG) in the presence or absence of 1.0 MAC isoflurane. Myocardial infarct size and superoxide anion production were measured using triphenyltetrazolium staining and confocal fluorescence microscopy, respectively.
RESULTS: Isoflurane (P < 0.05) decreased infarct size to 19 +/- 3% (mean +/- SEM) of the left ventricular area at risk as compared to the control (38 +/- 4%). 5-HD administered before but not after isoflurane abolished this beneficial effect (37 +/- 4% as compared to 24 +/- 3%). 5-HD alone had no effect on infarct size (42 +/- 3%). Isoflurane increased fluorescence intensity. Pretreatment with N-acetylcysteine, 2-MPG, or 5-HD before isoflurane abolished increases in fluorescence, but administration of 5-HD after isoflurane only partially attenuated increases in fluorescence produced by the volatile anesthetic agent.
CONCLUSIONS: The results indicate that mitochondrial K(ATP) channel opening acts as a trigger for isoflurane-induced preconditioning by generating ROS in vivo.
Author List
Tanaka K, Weihrauch D, Ludwig LM, Kersten JR, Pagel PS, Warltier DCAuthor
Dorothee Weihrauch DVM, PhD Research Scientist II in the Anesthesiology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Adenosine TriphosphatasesAnesthetics, Inhalation
Animals
Ethidium
Fluorescent Dyes
Free Radical Scavengers
Hemodynamics
Ion Channel Gating
Ischemic Preconditioning, Myocardial
Isoflurane
Male
Microscopy, Confocal
Mitochondria, Heart
Myocardial Infarction
Myocardium
Potassium Channels
Pulmonary Alveoli
Rabbits
Reactive Oxygen Species
