title: Substrate-specific impairment of mitochondrial respiration in permeabilized fibers from patients with coronary heart disease versus valvular disease.
abstract: High-resolution respirometry of permeabilized myocardial fibers offers reliable insights concerning the integrated mitochondrial function while using small amounts of cardiac tissue. The aim of the present study was to assess the respiratory function in permeabilized fibers of human right atrial appendages harvested from patients with coronary heart disease (CHD) (n = 6) versus patients with valvular disease (n = 5) and preserved ejection fraction that underwent non-emergency cardiac surgery. Human bundle samples (1-3 mg wet weight) permeabilized with saponin were transferred into the 2 ml Oxygraph-2 k chambers to measure complex I(CI) and II (CII)-dependent respiration, respectively. The following values (expressed in pmol/s mg) were obtained for CI-dependent respiration: oxidative phosphorylation (OXPHOS), 35.65 ± 1.10 versus 42.43 ± 1.08, electron transport system (ETS), 37.87 ± 1.72 versus. 46.58 ± 1.85, and respiratory control ratio (RCR, calculated as the ratio between OXPHOS and LEAK states), 2.43 ± 0.09 versus 2.73 ± 0.068 (p < 0.05). In conclusion, in patients with CHD we showed a significant decline for the OXPHOS capacity, ETS and RCR for mitochondria energized with CI (but not with CII) substrates. These observations are suggestive for an early impairment of complex I supported respiration in ischemic heart disease, as previously demonstrated in the setting of experimental ischemia/reperfusion in several animal species.
authors.affiliation: Department of Pathophysiology, Victor Babeş University of Medicine and Pharmacy, Timişoara, Romania.
authors.forename: Oana
authors.initials: O
authors.lastname: Duicu
authors.forename: Călin
authors.initials: C
authors.lastname: Juşcă
authors.forename: Lucian
authors.initials: L
authors.lastname: Falniţă
authors.forename: Silvia
authors.initials: S
authors.lastname: Mirică
authors.forename: Daniela
authors.initials: D
authors.lastname: Maximov
authors.forename: Ovidiu
authors.initials: O
authors.lastname: Firă-Mladinescu
authors.forename: Danina
authors.initials: D
authors.lastname: Muntean
mesh_terms: D000368:Aged; D050260:Carbohydrate Metabolism; D019069:Cell Respiration; D003324:Coronary Artery Disease / Q000378:metabolism* / Q000473:pathology; D004579:Electron Transport; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D006349:Heart Valve Diseases / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D066298:In Vitro Techniques; D008293:Malates / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism*; D010085:Oxidative Phosphorylation; D010101:Oxygen Consumption; D010539:Permeability; D012503:Saponins / Q000494:pharmacology
chemical_list: D008293:Malates; D012503:Saponins; D018698:Glutamic Acid; C030298:malic acid