Lopaschuk G D
University of Alberta, Edmonton, Canada.
Presse Med. 1998 Dec 12;27(39):2100-4.
THE ISCHEMIA-ENERGY RELATIONSHIP: A growing number of experimental and clinical studies have demonstrated that improving heart energy metabolism can have a positive effect on the consequences of myocardial ischemia. By enhancing myocardial carbohydrate metabolism, it is possible to improve cardiac function and/or limit tissue damage. It is known however that a high level of circulating fatty acids reduces myocardial glucose metabolism, a situation which is observed in most cases of symptomatic myocardial ischemia and which can further aggravate ischemic damage. PHARMACOLOGICAL OPTIONS: A certain number of pharmacological possibilities are available for stimulating glucose metabolism directly or indirectly by inhibiting fatty acid beta-oxidation. The effect of trimetazidine is based on this action and we have recently demonstrated in isolated perfused rat hearts with high concentrations of fatty acids that trimetazidine stimulates glucose oxidation. Clinical studies have also demonstrated that trimetazidine has a protective effect on heart tissue during episodes of myocardial ischemia. Pharmacologically improving cardiac energy metabolism with drugs such as trimetazidine could be a new promising approach to the treatment of cardiovascular diseases.
越来越多的实验和临床研究表明,改善心脏能量代谢对心肌缺血的后果具有积极影响。通过增强心肌碳水化合物代谢,有可能改善心脏功能和/或限制组织损伤。然而,众所周知,高水平的循环脂肪酸会降低心肌葡萄糖代谢,这种情况在大多数有症状的心肌缺血病例中都能观察到,并且会进一步加重缺血损伤。
有若干种药理学方法可通过抑制脂肪酸β氧化直接或间接刺激葡萄糖代谢。曲美他嗪的作用即基于此,我们最近在灌注有高浓度脂肪酸的离体大鼠心脏中证明,曲美他嗪可刺激葡萄糖氧化。临床研究也表明,曲美他嗪在心肌缺血发作期间对心脏组织具有保护作用。使用曲美他嗪等药物从药理学角度改善心脏能量代谢可能是治疗心血管疾病的一种新的有前景的方法。