Chagas Antonio C P, Dourado Paulo M M, Galvão Tatiana de Fátima Gonçalves
Heart Institute (InCor), University of São Paulo Medical School, São Paulo, Brazil.
Curr Pharm Des. 2008;14(25):2563-71. doi: 10.2174/138161208786071236.
Metabolic modulation during myocardial ischemia is possible by the use of specific drugs, which may induce a shift from free fatty acid towards predominantly glucose utilization by the myocardium to increase ATP generation per unit oxygen consumption. Three agents (trimetazidine, ranolazine, and perhexiline) have well-documented anti-ischaemic effects. However, perhexiline, the most potent agent currently available, requires plasma-level monitoring to avoid hepato-neuro-toxicity. Besides, the long-term safety of trimetazidine and ranolazine has yet to be established. In addition to their effect in ischemia, the potential use of these drugs in chronic heart failure is gaining recognition as clinical and experimental data are showing the improvement of myocardial function following treatment with several of them, even in the absence of ischemia. Future applications for this line of treatment is promising and deserves additional research. In particular, large, randomised, controlled trials investigating the effects of these agents on mortality and hospitalization rates due to coronary artery disease are needed.
通过使用特定药物可在心肌缺血期间实现代谢调节，这些药物可能促使心肌从主要利用游离脂肪酸转变为主要利用葡萄糖，以增加每单位氧消耗产生的三磷酸腺苷（ATP）。三种药物（曲美他嗪、雷诺嗪和哌克昔林）具有充分记录的抗缺血作用。然而，哌克昔林作为目前最有效的药物，需要监测血浆水平以避免肝神经毒性。此外，曲美他嗪和雷诺嗪的长期安全性尚未确立。除了对缺血的作用外，随着临床和实验数据表明其中几种药物治疗后心肌功能得到改善，即使在无缺血的情况下，这些药物在慢性心力衰竭中的潜在应用也越来越受到认可。这种治疗方法的未来应用前景广阔，值得进一步研究。特别是，需要进行大型随机对照试验，以研究这些药物对冠状动脉疾病导致的死亡率和住院率的影响。
