Aims: The addition of trimetazidine to standard treatment has been shown to improve left ventricular(LV) function in patients with heart failure. The aim of this study is to non-invasively assess, by means of in vivo ...Aims: The addition of trimetazidine to standard treatment has been shown to improve left ventricular(LV) function in patients with heart failure. The aim of this study is to non-invasively assess, by means of in vivo 31P-magnetic resonance spectroscopy(31P-MRS), the effects of trimetazidine on LV cardiac phosphocreatine and adenosine triphosphate(PCr/ATP) ratio in patients with heart failure. Methods and results: Twelve heart failure patients were randomized in a double-blind, cross-over study to placebo or trimetazidine(20 mg t.i.d.) for two periods of 90 days. At the end of each period, all patients underwent exercise testing, 2D echocardiography, and MRS. New York Heart Association(NYHA) class, ejection fraction(EF), maximal rate-pressure product, and metabolic equivalent system(METS) were evaluated. Relative concentrations of PCr and ATP were determined by cardiac 31P-MRS. On trimetazidine, NYHA class decreased from 3.04±0.26 to 2.45±0.52(P=0.005), whereas EF(34±10 vs. 39±10%, P=0.03) and METS(from 7.44±1.84 to 8.78±2.72, P=0.03) increased. The mean cardiac PCr/ATP ratio was 1.35±0.33 with placebo, but was increased by 33%to 1.80±0.50(P=0.03)with trimetazidine. Conclusion: Trimetazidine improves functional class and LV function in patients with heart failure. These effects are associated to the observed trimetazidi ne-induced increase in the PCr/ATP ratio, indicating preservation of the myocar dial high-energy phosphate levels.展开更多
低氧预适应是通过亚致死的低氧处理后,激活体内小分子内源性保护机制,让机体对接下来的更严重或致死性低氧刺激产生耐受/抗性。神经细胞是一种能接收和传导兴奋的细胞,对氧含量的变化十分敏感,其能量代谢随氧气变化较为显著。在低氧环境...低氧预适应是通过亚致死的低氧处理后,激活体内小分子内源性保护机制,让机体对接下来的更严重或致死性低氧刺激产生耐受/抗性。神经细胞是一种能接收和传导兴奋的细胞,对氧含量的变化十分敏感,其能量代谢随氧气变化较为显著。在低氧环境下,神经细胞的腺嘌呤核苷三磷酸(adenosinetriphosphate,ATP)合成减少可激活AMP激活的蛋白激酶[adenosine5’-monophosphate(AMP)-activated protein kinase,AMPK]和TSC1/TSC2复合体抑制哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin,mTOR)。mTOR的一个复合物mTOR复合体1(mTORC1)的表达对机体的能量代谢产生影响。低氧预适应,通过激活或抑制一些基因表达让神经细胞有效利用氧气,使机体产生低氧耐受。在氧浓度低的生存环境下,通过低氧预适应调节能量变化增加机体存活的可能性。高原、航空航天事业、水下作业以及病理性的低氧时,低氧预适应诱导相关分子变化可防止对氧有大量需求的脑组织发生病变,增加神经细胞的存活时间,减少死亡。展开更多
文摘Aims: The addition of trimetazidine to standard treatment has been shown to improve left ventricular(LV) function in patients with heart failure. The aim of this study is to non-invasively assess, by means of in vivo 31P-magnetic resonance spectroscopy(31P-MRS), the effects of trimetazidine on LV cardiac phosphocreatine and adenosine triphosphate(PCr/ATP) ratio in patients with heart failure. Methods and results: Twelve heart failure patients were randomized in a double-blind, cross-over study to placebo or trimetazidine(20 mg t.i.d.) for two periods of 90 days. At the end of each period, all patients underwent exercise testing, 2D echocardiography, and MRS. New York Heart Association(NYHA) class, ejection fraction(EF), maximal rate-pressure product, and metabolic equivalent system(METS) were evaluated. Relative concentrations of PCr and ATP were determined by cardiac 31P-MRS. On trimetazidine, NYHA class decreased from 3.04±0.26 to 2.45±0.52(P=0.005), whereas EF(34±10 vs. 39±10%, P=0.03) and METS(from 7.44±1.84 to 8.78±2.72, P=0.03) increased. The mean cardiac PCr/ATP ratio was 1.35±0.33 with placebo, but was increased by 33%to 1.80±0.50(P=0.03)with trimetazidine. Conclusion: Trimetazidine improves functional class and LV function in patients with heart failure. These effects are associated to the observed trimetazidi ne-induced increase in the PCr/ATP ratio, indicating preservation of the myocar dial high-energy phosphate levels.
文摘低氧预适应是通过亚致死的低氧处理后,激活体内小分子内源性保护机制,让机体对接下来的更严重或致死性低氧刺激产生耐受/抗性。神经细胞是一种能接收和传导兴奋的细胞,对氧含量的变化十分敏感,其能量代谢随氧气变化较为显著。在低氧环境下,神经细胞的腺嘌呤核苷三磷酸(adenosinetriphosphate,ATP)合成减少可激活AMP激活的蛋白激酶[adenosine5’-monophosphate(AMP)-activated protein kinase,AMPK]和TSC1/TSC2复合体抑制哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin,mTOR)。mTOR的一个复合物mTOR复合体1(mTORC1)的表达对机体的能量代谢产生影响。低氧预适应,通过激活或抑制一些基因表达让神经细胞有效利用氧气,使机体产生低氧耐受。在氧浓度低的生存环境下,通过低氧预适应调节能量变化增加机体存活的可能性。高原、航空航天事业、水下作业以及病理性的低氧时,低氧预适应诱导相关分子变化可防止对氧有大量需求的脑组织发生病变,增加神经细胞的存活时间,减少死亡。
