Wang Wei, Lopaschuk Gary D
University of Alberta, 423 Heritage Medical Research Center, Edmonton, Alberta T6G 2S2, Canada.
Expert Rev Cardiovasc Ther. 2007 Nov;5(6):1123-34. doi: 10.1586/14779072.5.6.1123.
Ischemic heart disease is a major cause of morbidity and mortality in the world. Most of the existing therapeutic strategies used to treat ischemic heart disease aim at either increasing the oxygen supply to the heart (thrombolysis, revascularization, angiotensin converting enzyme inhibition and antiplatelet therapy) or decreasing the oxygen demand of the heart (beta-blockers and nitrates). Despite the fact that a compromised energy supply to the heart muscle is central to the pathology of ischemic heart disease, therapeutic approaches that focus on altering cardiac energy metabolism have not seen major clinical use. Therapeutic strategies in which the efficiency of oxygen utilization by the heart is enhanced could theoretically benefit the ischemic heart, and could have an additive benefit to existing therapeutic strategies. The energy supply for the heart (in the form of ATP) is normally provided by the balanced metabolism of both fatty acids (major part) and carbohydrates (minor part) oxidation. During reperfusion, this balance is broken by the dramatic enhancement of fatty acid oxidation and attenuation of carbohydrate oxidation, which results in intracellular H(+) accumulation and Ca(2+) overload. This article reviews the alterations in cardiac energy metabolism that occur in the ischemic heart, and discusses the existing and proposed pharmacologic therapies to optimize the balance of fatty acids and carbohydrate oxidation for the treatment of ischemic heart diseases.
缺血性心脏病是全球发病和死亡的主要原因。目前用于治疗缺血性心脏病的大多数治疗策略旨在增加心脏的氧气供应（溶栓、血运重建、血管紧张素转换酶抑制和抗血小板治疗）或降低心脏的氧气需求（β受体阻滞剂和硝酸盐）。尽管心肌能量供应受损是缺血性心脏病病理的核心，但专注于改变心脏能量代谢的治疗方法尚未得到广泛的临床应用。从理论上讲，提高心脏氧利用效率的治疗策略可能会使缺血性心脏受益，并且可能对现有治疗策略产生附加益处。心脏的能量供应（以ATP的形式）通常由脂肪酸（主要部分）和碳水化合物（次要部分）氧化的平衡代谢提供。在再灌注期间，这种平衡被脂肪酸氧化的急剧增强和碳水化合物氧化的减弱打破，这导致细胞内H(+)积累和Ca(2+)过载。本文综述了缺血性心脏中发生的心脏能量代谢变化，并讨论了现有的和提议的药物治疗方法，以优化脂肪酸和碳水化合物氧化的平衡，用于治疗缺血性心脏病。
