title: Trimetazidine does not alter metabolic substrate oxidation in cardiac mitochondria of target patient population.
abstract: OBJECTIVE
  Trimetazidine, known as a metabolic modulator, is an anti-anginal drug used for treatment of stable coronary artery disease (CAD). It is proposed to act via modulation of cardiac metabolism, shifting the mitochondrial substrate utilization towards carbohydrates, thus increasing the efficiency of ATP production. This mechanism was recently challenged; however, these studies used indirect approaches and animal models, which made their conclusions questionable. The goal of the current study was to assess the effect of trimetazidine on mitochondrial substrate oxidation directly in left ventricular myocardium from CAD patients.
  
  
  METHODS
  Mitochondrial fatty acid (palmitoylcarnitine) and carbohydrate (pyruvate) oxidation were measured in permeabilized left ventricular fibres obtained during coronary artery bypass grafting surgery from CAD patients, which either had trimetazidine included in their therapy (TMZ group) or not (Control).
  
  
  RESULTS
  There was no difference between the two groups in the oxidation of either palmitoylcarnitine or pyruvate, and in the ratio of carbohydrate to fatty acid oxidation. Activity and expression of pyruvate dehydrogenase, the key regulator of carbohydrate metabolism, were also not different. Lastly, acute in vitro exposure of myocardial tissue to different concentrations of trimetazidine did not affect myocardial oxidation of fatty acid.
  
  
  CONCLUSIONS
  Using myocardial tissue from CAD patients, we found that trimetazidine (applied chronically in vivo or acutely in vitro) had no effect on cardiac fatty acid and carbohydrate oxidation, suggesting that the clinical effects of trimetazidine are unlikely to be due to its metabolic effects, but rather to an as yet unidentified intracardiac mechanism.
authors: Department of Integrative Physiology, University of Split School of Medicine, Split, Croatia.
authors: M
authors: M
authors: Cavar
authors: Department of Integrative Physiology, University of Split School of Medicine, Split, Croatia.
authors: M
authors: M
authors: Ljubkovic
authors: Department of Cardiac Surgery, University Hospital Split, Split, Croatia.
authors: C
authors: C
authors: Bulat
authors: Department of Integrative Physiology, University of Split School of Medicine, Split, Croatia.|Department of Cardiology, University Hospital Split, Split, Croatia.
authors: D
authors: D
authors: Bakovic
authors: Department of Cardiology, University Hospital Split, Split, Croatia.
authors: D
authors: D
authors: Fabijanic
authors: Department of Integrative Physiology, University of Split School of Medicine, Split, Croatia.
authors: J
authors: J
authors: Kraljevic
authors: Department of Anaesthesiology, University Hospital Split, Split, Croatia.
authors: N
authors: N
authors: Karanovic
authors: Department of Integrative Physiology, University of Split School of Medicine, Split, Croatia.
authors: Z
authors: Z
authors: Dujic
authors: Department of Cardiovascular Diseases, John Ochsner Heart and Vascular Institute, Ochsner Clinical School-the University of Queensland School of Medicine, New Orleans, LA, USA.
authors: C J
authors: CJ
authors: Lavie
authors: K.G. Jebsen Center of Exercise in Medicine, Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway.
authors: U
authors: U
authors: Wisloff
authors: Department of Integrative Physiology, University of Split School of Medicine, Split, Croatia.
authors: J
authors: J
authors: Marinovic
mesh_terms: D000368:Aged; D003324:Coronary Artery Disease / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects* / Q000378:metabolism*; D010084:Oxidation-Reduction / Q000187:drug effects; D010172:Palmitoylcarnitine / Q000378:metabolism; D019289:Pyruvic Acid / Q000378:metabolism; D014292:Trimetazidine / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D010172:Palmitoylcarnitine; D019289:Pyruvic Acid; D014292:Trimetazidine