PT  - JOURNAL ARTICLE
AU  - Ramesh Saeedi
AU  - Mark Grist
AU  - Richard B. Wambolt
AU  - Anne Bescond-Jacquet
AU  - Arnaud Lucien
AU  - Michael F. Allard
TI  - Trimetazidine Normalizes Postischemic Function of Hypertrophied Rat Hearts
AID  - 10.1124/jpet.104.082636
DP  - 2005 Jul 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 446--454
VI  - 314
IP  - 1
4099  - http://jpet.aspetjournals.org/content/314/1/446.short
4100  - http://jpet.aspetjournals.org/content/314/1/446.full
SO  - J Pharmacol Exp Ther2005 Jul 01; 314
AB  - The fraction of glucose passing through glycolysis that is oxidized is low in hypertrophied hearts, a pattern of glucose use associated with poor postischemic contractile function. We tested the hypothesis that trimetazidine, a partial 3-ketoacyl coenzyme A thiolase inhibitor, would stimulate glucose oxidation and, thereby, improve fractional glucose oxidation and postischemic function of hypertrophied hearts. Function, glycolysis, and oxidation of glucose, lactate, and palmitate were measured before and after global no-flow ischemia in isolated working hearts from sham-operated (control) and aortic-constricted (hypertrophied) male Sprague-Dawley rats in the presence or absence of 1 μM trimetazidine. Heart function was significantly improved by trimetazidine after ischemia, but only in hypertrophied hearts, with function improving to values in untreated control hearts. This effect occurred in association with relatively minor changes in oxidative metabolism. However, trimetazidine reduced glycolysis by ∼30% but did so only in hypertrophied hearts, an unexpected novel action of this agent that resulted in a larger fractional oxidation of glucose, effectively normalizing it in hypertrophied hearts. Thus, trimetazidine normalizes postischemic function and fractional glucose oxidation in hypertrophied hearts, mainly by reducing glycolysis. These data extend the potential usefulness of trimetazidine and provide support for its use as a means to improve postischemic function of pressure overload hypertrophied hearts. The American Society for Pharmacology and Experimental Therapeutics