title: Mitochondrial involvement in propofol-induced cardioprotection: An in vitro study in human myocardium.
abstract: Propofol has been shown to exert cardioprotection, but the underlying mechanisms remain incompletely understood. We examined: (1) whether propofol-induced cardioprotection depended on the time and the dose of administration; (2) the role of mitochondrial adenosine triphosphate-sensitive potassium channels, nitric oxide synthase, and mitochondrial respiratory chain activity in propofol-induced cardioprotection. Human right atrial trabeculae were obtained during cardiopulmonary bypass for coronary artery bypass and aortic valve replacement. Isometric force of contraction of human right atrial trabeculae hanged in an oxygenated Tyrode's solution was recorded during 30-min hypoxia and 60-min reoxygenation (Control). Propofol 0.1, 1, and 10 µM was administered: (1) 5 min before hypoxia until the end of the experiment; (2) 5 min followed by 5-min washout before hypoxia; (3) during the reoxygenation period, propofol 10 µM was administered in presence of 5-hydroxydecanoate (antagonist of mitochondrial adenosine triphosphate-sensitive potassium channels), and NG-nitro-L-arginine methyl ester (inhibitor of nitric oxide synthase). In addition, mitochondria were isolated from human right atrial at 15 min of reoxygenation. The effect of propofol on activity of the mitochondrial respiratory chain complexes was evaluated by spectrophotometry. The force of contraction (% of baseline) and the complex activity between the different groups were compared with an analysis of variance and post hoc test. Propofol 10 µM administered during the reoxygenation period significantly improved the recovery of force of contraction at the end of reoxygenation (82 ± 6% of baseline value vs. 49 ± 6% in Control; P < 0.001). The beneficial effects of propofol 10 µM were abolished by co-administration with 5-hydroxydecanoate (53 ± 8%) or NG-nitro-L-arginine methyl ester (57 ± 6%). Propofol 10 µM significantly increased enzymatic activities of the mitochondrial respiratory chain complexes, in reoxygenation period, compared to their respective untreated controls. In conclusion, in human myocardium, propofol-induced cardioprotection was mediated by mitochondrial adenosine triphosphate-sensitive potassium channels opening, nitric oxide synthase activation and stimulation of mitochondrial respiratory chain complexes, in early reoxygenation period.
authors.affiliation: Department of Anesthesiology and Intensive Care, Centre Hospitalier Universitaire de Caen, Faculty of Medicine, Normandie Université, EA4650, Caen 14033, France sand.lemoine2@wanadoo.fr.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Lemoine
authors.affiliation: Department of Anesthesiology and Intensive Care, Centre Hospitalier Universitaire de Caen, Faculty of Medicine, Normandie Université, EA4650, Caen 14033, France.
authors.forename: Lan
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Department of Anesthesiology and Intensive Care, Centre Hospitalier Universitaire de Caen, Faculty of Medicine, Normandie Université, EA4650, Caen 14033, France.
authors.forename: Steeve
authors.initials: S
authors.lastname: Gress
authors.affiliation: Department of Anesthesiology and Intensive Care, Centre Hospitalier Universitaire de Caen, Faculty of Medicine, Normandie Université, EA4650, Caen 14033, France.
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Gérard
authors.affiliation: Department of Biochemistry, Centre Hospitalier Universitaire de Caen, Faculty of Medicine, Normandie Université, EA4650, Caen 14033, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Allouche
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Hanouz
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004579:Electron Transport / Q000187:drug effects*; D005260:Female; D006321:Heart / Q000187:drug effects*; D006801:Humans; D000860:Hypoxia; D054086:KATP Channels / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000201:enzymology; D009200:Myocardial Contraction / Q000187:drug effects*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D015742:Propofol / Q000494:pharmacology*
chemical_list: D018686:Anesthetics, Intravenous; D002316:Cardiotonic Agents; D054086:KATP Channels; D019001:Nitric Oxide Synthase; D015742:Propofol
keywords: Propofol; cardioprotection; mitochondrial adenosine triphosphate-sensitive potassium channels; mitochondrial respiratory chain complexes