Key result
Trimetazidine attenuates myocardial metabolic disturbance and inhibits NPY upregulation in acute pressure overload.
Why the study?
The temporal association between myocardial metabolism remodeling and ventricular hypertrophy following cardiac pressure overload and the potential effect of trimetazidine on this process were not confirmed.
Does trimetazidine improve myocardial energy dysfunction in a rat model of cardiac pressure overload?
Does trimetazidine improve myocardial energy dysfunction in a rat model of cardiac pressure overload?
Trimetazidine may attenuate early cardiac energy dysfunction and metabolic remodeling following pressure overload via regulation of the neuropeptide Y system in a preclinical model.
Trimetazidine may attenuate early energy dysfunction in rat overload; leaves open clinical translation and human trials.
BACKGROUND: Metabolism remodeling has been recognized as an early event following cardiac pressure overload. However, its temporal association with ventricular hypertrophy has not been confirmed. Moreover, whether trimetazidine could favorably affect this process also needs to be determined. The aim of the study was to explore the temporal changes of myocardial metabolism remodeling following pressure-overload induced ventricular hypertrophy and the potential favorable effect of trimetazidine on myocardial metabolism remodeling. METHODS: A rat model of abdominal aortic constriction (AAC)-induced cardiac pressure overload was induced. These rats were grouped as the AAC (no treatment) or TMZ group according to whether oral trimetazidine (TMZ, 40 mg/kg/d, for 5 days) was administered. Changes in cardiac structures were sequentially evaluated via echocardiography. The myocardial ADP/ATP ratio was determined to reflect the metabolic status, and changes in serum neuropeptide Y systems were evaluated. RESULTS: Myocardial metabolic disorder was acutely induced as evidenced by an increased ADP/ATP ratio within 7 days of AAC before the morphological changes in the myocardium, accompanied by up-regulation of serum oxidative stress markers and expression of fetal genes related to hypertrophy. Moreover, the serum NPY and myocardial NPY-1R, 2R, and 5R levels were increased within the acute phase of AAC-induced cardiac pressure overload. Pretreatment with TMZ could partly attenuate myocardial energy metabolic homeostasis, decrease serum levels of oxidative stress markers, attenuate the induction of hypertrophy-related myocardial fetal genes, inhibit the up-regulation of serum NPY levels, and further increase the myocardial expression of NPY receptors. CONCLUSIONS: Cardiac metabolic remodeling is an early change in the myocardium before the presence of typical morphological ventricular remodeling following cardiac pressure overload, and pretreatment with TMZ may at least partly reverse the acute metabolic disturbance, perhaps via regulation of the NPY system.
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Chen et al. (2016) studied Cardiac pressure overload (n=38). Trimetazidine vs. No treatment (AAC only) and sham surgery was evaluated on Myocardial ADP/ATP ratio (p=<0.05). Pretreatment with trimetazidine significantly attenuated myocardial energy metabolic disturbance and inhibited the up-regulation of serum neuropeptide Y levels in a rat model of acute cardiac pressure overload.
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