title: The influence of mitochondrial KATP-channels in the cardioprotection of preconditioning and postconditioning by sevoflurane in the rat in vivo.
abstract: Volatile anesthetics induce myocardial preconditioning and can also protect the heart when given at the onset of reperfusion-a practice recently termed "postconditioning." We investigated the role of mitochondrial KATP (mKATP)-channels in sevoflurane-induced cardioprotection for both preconditioning and postconditioning alone and whether there is a synergistic effect of both. Rats were subjected to 25 min of coronary artery occlusion followed by 120 min of reperfusion. Infarct size was determined by triphenyltetrazolium staining. The following protocols were used: 1) preconditioning (S-Pre, n = 10, achieved by 2 periods of 5 min sevoflurane administration (1 MAC) followed by 10 min of washout); 2) sevoflurane postconditioning (1 MAC of sevoflurane given for 2 min at the beginning of reperfusion; S-Post, n = 10); 3) administration before and after ischemia (S-Pre + S-Post, n = 10). Protocols 1-3 were repeated in the presence of 5-hydroxydecanoate (5HD), a specific mKATP-channel-blocker (S-Pre + S-Post + 5HD, S-Pre + 5HD: n = 10; S-Post + 5HD: n = 9). Nine rats served as untreated controls (CON) or received 5HD alone (5HD, n = 10). Both S-Pre (23% +/- 13% of the area at risk, mean +/- sd) and S-Post (18% +/- 5%) reduced infarct size compared with CON (49% +/- 11%, both P < 0.05). S-Pre + S-Post resulted in a larger reduction of infarct size (12% +/- 5%, P = 0.054 versus S-Pre) compared with administration before or after ischemia alone. 5HD diminished the protection in all three sevoflurane treated groups (S-Pre + 5HD, 35% +/- 12%; S-Post + 5HD, 44% +/- 12%; S-Pre + S-Post + 5HD, 46% +/- 14%;) but given alone had no effect on infarct size (41% +/- 13%). Sevoflurane preconditioning and postconditioning protects against myocardial ischemia-reperfusion injury. The combination of preconditioning and postconditioning provides additive cardioprotection and is mediated, at least in part, by mKATP-channels.
authors.affiliation: Klinik für Anaesthesiologie, Universitätsklinikum Düsseldorf, Düsseldorf, Germany.
authors.forename: Detlef
authors.initials: D
authors.lastname: Obal
authors.forename: Saskia
authors.initials: S
authors.lastname: Dettwiler
authors.forename: Christian
authors.initials: C
authors.lastname: Favoccia
authors.forename: Horst
authors.initials: H
authors.lastname: Scharbatke
authors.forename: Benedikt
authors.initials: B
authors.lastname: Preckel
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Schlack
mesh_terms: D000255:Adenosine Triphosphate / Q000502:physiology*; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D008738:Methyl Ethers / Q000494:pharmacology*; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D015221:Potassium Channels / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species; D000077149:Sevoflurane; D014655:Vascular Resistance; D016277:Ventricular Function, Left
chemical_list: D018685:Anesthetics, Inhalation; D008738:Methyl Ethers; D015221:Potassium Channels; D017382:Reactive Oxygen Species; D000077149:Sevoflurane; D000255:Adenosine Triphosphate; D019869:Phosphatidylinositol 3-Kinases