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Trimetazidine normalizes postischemic function of hypertrophied rat hearts
Ramesh Saeedi1, Mark Grist, Richard B Wambolt
1James Hogg iCAPTURE Centre for Cardiovascular and Pulmonary Research, Department of Pathology and Laboratory Medicine, University of British Columbia-St. Paul's Hospital, Vancouver, BC, Canada.
The Journal of Pharmacology and Experimental Therapeutics
|April 21, 2005
Summary
Trimetazidine improves heart function after ischemia in hypertrophied hearts by reducing glycolysis, which normalizes glucose oxidation. This suggests trimetazidine can enhance postischemic recovery in pressure overload conditions.
Area of Science:
- Cardiology
- Biochemistry
- Pharmacology
Background:
- Hypertrophied hearts exhibit reduced glucose oxidation via glycolysis, correlating with impaired postischemic contractile function.
- Understanding metabolic alterations in cardiac hypertrophy is crucial for developing therapeutic strategies.
Purpose of the Study:
- To investigate if trimetazidine, a 3-ketoacyl coenzyme A thiolase inhibitor, can improve fractional glucose oxidation and postischemic function in hypertrophied hearts.
- To elucidate the mechanism by which trimetazidine affects cardiac metabolism and function.
Main Methods:
- Isolated working hearts from sham-operated and aortic-constricted rats were subjected to global no-flow ischemia.
- Measurements included heart function, glycolysis, and oxidation of glucose, lactate, and palmitate, with and without trimetazidine treatment.
- Comparative analysis between control and hypertrophied hearts, with and without trimetazidine.
Main Results:
- Trimetazidine significantly improved postischemic heart function in hypertrophied hearts to levels seen in untreated control hearts.
- Trimetazidine reduced glycolysis by approximately 30% in hypertrophied hearts, an unexpected finding.
- This reduction in glycolysis led to increased fractional glucose oxidation, normalizing it in hypertrophied hearts.
Conclusions:
- Trimetazidine normalizes postischemic function and fractional glucose oxidation in hypertrophied hearts primarily by reducing glycolysis.
- These findings support the potential of trimetazidine in improving postischemic function in pressure overload-induced cardiac hypertrophy.