Lopaschuk G D
Department of Pediatrics, Faculty of Medicine, The University of Alberta, Edmonton, Canada.
Am J Cardiol. 1998 Sep 3;82(5A):14K-17K. doi: 10.1016/s0002-9149(98)00532-3.
An increasing number of clinical and experimental studies have shown that optimizing energy metabolism in the heart is an effective approach to decreasing the symptoms associated with myocardial ischemia. In particular, increasing myocardial glucose metabolism can benefit heart function and/or lessen tissue injury. However, high levels of circulating fatty acids will markedly decrease glucose metabolism in the heart. These high levels of fatty acids occur in most clinically relevant conditions of myocardial ischemia, and can contribute to the severity of ischemic injury. A number of pharmacologic agents are now available that directly stimulate myocardial glucose metabolism or indirectly stimulate glucose metabolism secondary to an inhibition of fatty acid metabolism. One agent that appears to act by this mechanism is trimetazidine, which we recently found stimulates glucose oxidation in isolated rat hearts perfused with high levels of fatty acids. Clinical studies have also shown that trimetazidine has cardioprotective effects in the setting of myocardial ischemia. As a result, optimizing energy metabolism with agents such as trimetazidine may have considerable promise as a new approach to treating cardiovascular disease.
越来越多的临床和实验研究表明，优化心脏能量代谢是减轻心肌缺血相关症状的有效方法。特别是，增加心肌葡萄糖代谢可改善心脏功能和/或减轻组织损伤。然而，循环脂肪酸水平升高会显著降低心脏中的葡萄糖代谢。在大多数与临床相关的心肌缺血情况下都会出现这些高水平的脂肪酸，并且会加重缺血性损伤的严重程度。现在有多种药物可直接刺激心肌葡萄糖代谢或通过抑制脂肪酸代谢间接刺激葡萄糖代谢。曲美他嗪似乎就是通过这种机制起作用的一种药物，我们最近发现它能刺激在高脂肪酸水平灌注下的离体大鼠心脏中的葡萄糖氧化。临床研究也表明，曲美他嗪在心肌缺血情况下具有心脏保护作用。因此，用曲美他嗪等药物优化能量代谢作为治疗心血管疾病的新方法可能有很大前景。
