title: Propofol-induced mitochondrial and contractile dysfunction of the rat ventricular myocardium.
abstract: Propofol is a short-acting hypnotic agent used in human medicine for sedation and general anesthesia. Its administration can be associated with serious cardiovascular side-effects that include decrease in arterial blood pressure and cardiac output. The aim of the present study was to evaluate propofol effects on mitochondrial respiration, myocardial contractility and electrophysiology in the same samples isolated from the heart ventricles of adult rats. Mitochondrial oxygen consumption was measured in permeabilized samples dissected from free walls of both ventricles using high-resolution respirometry. State LEAK was determined with malate and glutamate. Active respiration was induced by ADP (state PI) and further by succinate, a Complex II substrate (PI+II). Rotenone was injected to measure state PII. Antimycin A, a Complex III inhibitor was used to determine residual oxygen consumption (ROX). N,N,N',N'-tetramethyl-p-phenylenediamine dihydrochloride and ascorbate were injected simultaneously for respirometric assay of cytochrome c oxidase activity (CIV). Isometric contractions and membrane potentials were determined on multicellular preparations isolated from right and left ventricles. Propofol concentrations used ranged from 0.005 to 0.5 mmol/l. All respiratory parameters were significantly higher in the left control ventricles compared to the right ones. Propofol significantly decreased Complex I activity at concentration 0.025 mmol/l and papillary muscle contraction force at 0.1 mmol/l. Propofol did not affect action potential duration at any concentration studied. Our study suggests that mechanisms contributing to the impaired myocardial contraction during propofol anesthesia might include also mitochondrial dysfunction manifested by compromised activity of the respiratory Complex I.
authors.affiliation: Department of Physiology, Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic. jitka.kuncova@lfp.cuni.cz.
authors.forename: M
authors.initials: M
authors.lastname: Grundmanová
authors.forename: D
authors.initials: D
authors.lastname: Jarkovská
authors.forename: A
authors.initials: A
authors.lastname: Süß
authors.forename: Z
authors.initials: Z
authors.lastname: Tůma
authors.forename: M
authors.initials: M
authors.lastname: Marková
authors.forename: Z
authors.initials: Z
authors.lastname: Grundman
authors.forename: A
authors.initials: A
authors.lastname: El-Kadi
authors.forename: M
authors.initials: M
authors.lastname: Čedíková
authors.forename: M
authors.initials: M
authors.lastname: Štengl
authors.forename: J
authors.initials: J
authors.lastname: Kuncová
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D002302:Cardiac Output / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D006352:Heart Ventricles / Q000187:drug effects* / Q000503:physiopathology; D006993:Hypnotics and Sedatives / Q000633:toxicity*; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects* / Q000502:physiology; D009200:Myocardial Contraction / Q000187:drug effects* / Q000502:physiology; D010101:Oxygen Consumption / Q000187:drug effects* / Q000502:physiology; D015742:Propofol / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D006993:Hypnotics and Sedatives; D015742:Propofol