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Long-term therapy with trimetazidine in cardiomyopathic Syrian hamster BIO 14:6
N D'hahan1, K Taouil, A Dassouli
1Laboratoire de Biologie, Ecole Centrale de Paris, Châtenay-Malabry, France.
Insights
Trimetazidine treatment significantly improved survival and reduced heart and liver hypertrophy in cardiomyopathic Syrian hamsters by normalizing calcium levels. This suggests trimetazidine
Area of Science:
- Cardiovascular Research
- Pharmacology
- Animal Models
Background:
- The cardiomyopathic Syrian hamster (CMH) strain BIO 14:6 exhibits cardiac and skeletal muscle abnormalities, reduced longevity, and significant cardiac and liver hypertrophy.
- CMH hamsters develop substantial calcium (Ca2+) overload, with elevated total and cytosolic Ca2+ concentrations by 220 days of age.
Purpose of the Study:
- To investigate the efficacy of trimetazidine, an anti-ischaemic drug, in ameliorating cardiomyopathic conditions in CMH.
- To compare the effects of trimetazidine with the Ca2+ blocker verapamil in this animal model.
Main Methods:
- Long-term oral administration of trimetazidine (18 mg/kg/day) from 30 to 350 days of age in CMH.
- Assessment of survival rates, cardiac and liver hypertrophy, and intracellular Ca2+ levels in treated CMH compared to controls and verapamil-treated groups.
Main Results:
- Trimetazidine significantly increased the median survival time of CMH by 57% and completely resolved cardiac and liver hypertrophy.
- Trimetazidine treatment normalized total Ca2+ levels to those of healthy hamsters and reduced cytosolic Ca2+ overload to approximately twofold the normal level.
- Trimetazidine demonstrated superior efficacy compared to verapamil in improving survival and reducing hypertrophy.
Conclusions:
- Trimetazidine exhibits significant anti-Ca2+ properties and effectively improves survival and reduces hypertrophy in the CMH model.
- These findings suggest trimetazidine's potential therapeutic value in preventing congestive heart failure with similar underlying aetiologies.
Abstract:
The cardiomyopathic Syrian hamster (CMH) of the strain BIO 14:6 is a model for both cardiac and skeletal muscle abnormalities. It has reduced longevity and noticeable hypertrophy of the heart and liver. At 220 days, CMHs display a total Ca2+ overload, 1.3-1.8-fold normal and a cytosolic Ca2+ concentration 2-4-fold higher than normal. Long-term oral treatment (18 mg/kg per day) with trimetazidine (anti-ischaemic drug), from age 30 to 350 days, was more efficient than the standard Ca2+ blocker verapamil. Trimetazidine increased the median survival time of CMH by 57% and the hypertrophy disappeared. The total Ca2+ level in CMHs reverted to that of normal Syrian hamsters (F1B). The cytosolic Ca2+ overload was limited to a factor of approximately 2. Therefore, trimetazidine possesses anti-Ca2+ properties and is effective in increasing survival and decreasing the heart and liver hypertrophy of CMH. This suggests that trimetazidine may be valuable in the prevention of congestive heart failure of similar aetiology.