Pogatsa G
Gottsegen György National Institute of Cardiology, Research Department, Budapest, Hungary.
Coron Artery Dis. 2001 Feb;12 Suppl 1:S29-33.
Diabetic alterations of myocardial metabolism result mainly from malfunctions of acetyl-coenzyme A carboxylase, carnitine-palmitoyl-transferase-I and pyruvate-dehydrogenase inducing an overshoot of fatty acid oxidation that inhibits glucose oxidation. Gene expression of pyruvate-dehydrogenase and glucose transporters and depression of the third step of the mitochondrial respiratory chain also contribute to the diabetic alterations of myocardial metabolism. Ischaemic cardiovascular alterations are common and treatment is rarely successful in cases of diabetes since fatty acid oxidation is the costliest metabolic pathway for oxygen. Thus, in diabetes, aerobic glycolysis gradually shifts to anaerobic glycolysis under ischaemia, with accumulation of lactate and acid metabolites that in turn induce myocardial deterioration, Animal experiments have demonstrated that elective depression of activity of carnitine-palmitoyl-transferase-I enzyme-activity promotes glucose oxidation and early rapid recovery of myocardial contractility, especially under diabetic conditions. To reduce diabetic alterations of myocardial metabolism, anti-diabetic treatment must be switched to insulin during the acute ischaemic and post-ischaemic period of coronary diseases. Trimetazidine optimizes energy metabolism by selectively inhibiting action of the 3-ketoacyl-coenzyme A thiolase enzyme involved in beta-oxidation and inhibiting the overshoot of fatty oxidation. Trimetazidine, as the first 3-ketoacyl-coenzyme A thiolase inhibitor, therefore provides permanent myocardial cytoprotection in stable angina pectoris. However, in our experience, this beneficial anti-anginal effect is only observed in well-controlled situations.
心肌代谢的糖尿病性改变主要源于乙酰辅酶A羧化酶、肉碱-棕榈酰转移酶-I和丙酮酸脱氢酶的功能异常，导致脂肪酸氧化过度，从而抑制葡萄糖氧化。丙酮酸脱氢酶和葡萄糖转运蛋白的基因表达以及线粒体呼吸链第三步的抑制也促成了心肌代谢的糖尿病性改变。缺血性心血管改变很常见，而糖尿病患者的治疗很少成功，因为脂肪酸氧化是最消耗氧气的代谢途径。因此，在糖尿病中，缺血时有氧糖酵解会逐渐转变为无氧糖酵解，乳酸和酸性代谢产物积累，进而导致心肌恶化。动物实验表明，选择性抑制肉碱-棕榈酰转移酶-I的活性可促进葡萄糖氧化，并使心肌收缩力早期快速恢复，尤其是在糖尿病条件下。为减少心肌代谢的糖尿病性改变，在冠心病急性缺血期和缺血后期，抗糖尿病治疗必须改用胰岛素。曲美他嗪通过选择性抑制参与β氧化的3-酮酰基辅酶A硫解酶的作用并抑制脂肪酸氧化过度，从而优化能量代谢。因此，曲美他嗪作为首个3-酮酰基辅酶A硫解酶抑制剂，可在稳定型心绞痛中提供永久性心肌细胞保护。然而，根据我们的经验，这种有益的抗心绞痛作用仅在控制良好的情况下才能观察到。
