Trimetazidine does not alter metabolic substrate oxidation in cardiac mitochondria of target patient population

Cavar, M., Ljubkovic, M., Bulat, C., Bakovic, D., Fabijanic, D., Kraljevic, J., Karanovic, N., Dujic, Z., Lavie, C. J., Wisloff, U. and Marinovic, J. (2016) Trimetazidine does not alter metabolic substrate oxidation in cardiac mitochondria of target patient population. British Journal of Pharmacology, 173 9: 1529-1540. doi:10.1111/bph.13454

Author Cavar, M.
Ljubkovic, M.
Bulat, C.
Bakovic, D.
Fabijanic, D.
Kraljevic, J.
Karanovic, N.
Dujic, Z.
Lavie, C. J.
Wisloff, U.
Marinovic, J.
Title Trimetazidine does not alter metabolic substrate oxidation in cardiac mitochondria of target patient population
Journal name British Journal of Pharmacology   Check publisher's open access policy
ISSN 1476-5381
Publication date 2016-05-01
Year available 2016
Sub-type Article (original research)
DOI 10.1111/bph.13454
Open Access Status Not Open Access
Volume 173
Issue 9
Start page 1529
End page 1540
Total pages 12
Place of publication Chichester, West Sussex United Kingdom
Publisher John Wiley & Sons
Language eng
Formatted abstract
Background and Purpose
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.

Experimental Approach
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).

Key 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.

Conclusion and Implications
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.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
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