Therapeutic effects of L-carnitine and propionyl-L-carnitine on cardiovascular diseases: A review
Therapeutic effects of L-carnitine and propionyl-L-carnitine on cardiovascular diseases: A review
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DOI：
10.1196/annals.1320.007
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发表时间：
2004-01-01
期刊：
影响因子：
--
通讯作者：
Ceconi, C
中科院分区：
文献类型：
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作者：
Ferrari, R;Merli, E;Ceconi, C
多项实验研究表明，左卡尼汀通过抵消缺血时发生的高水平游离脂肪酸的毒性作用和改善碳水化合物代谢，减少缺血和再灌注后的心肌损伤。除了增加脂肪酸转运到线粒体的速率外，左卡尼汀还降低线粒体内乙酰辅酶A与游离辅酶A的比例，从而刺激丙酮酸脱氢酶的活性并增加丙酮酸的氧化。向心肌补充左卡尼汀可增加组织肉毒碱含量，防止高能磷酸盐储存的损失、缺血性损伤，并改善心脏再灌注恢复。临床上，左卡尼汀已被证明具有抗缺血特性。在小型短期研究中，左卡尼汀可作为抗心绞痛药，降低 ST 段压低和左心室舒张末压。这些短期研究还表明，接受运动测试或心房起搏的冠状动脉疾病患者左卡尼汀会释放乳酸。这些心脏保护作用在主动脉冠状动脉搭桥术和急性心肌梗塞中得到了证实。在一项对 472 名患者进行的随机多中心试验中，急性心肌梗死后早期开始左卡尼汀治疗（最初 5 天静脉输注 9 克/天，接下来的 12 个月每天口服 6 克），可减弱左心室扩张并防止心室重构。在接受治疗的患者中。出院后死亡和慢性心力衰竭的综合发生率呈下降趋势。左卡尼汀可以通过以下方式改善缺血和再灌注：(1) 防止长链酰基辅酶A的积累，这有利于受损线粒体产生自由基：(2) 改善氧化诱导的膜磷脂损伤的修复机制：(3) 抑制因心肌内或长链酰基辅酶A的积累而引起的恶性心律失常：(4) 减少缺血诱导的细胞凋亡和随之而来的心肌细胞重塑左心室。丙酰-L-肉碱是一种肉碱衍生物，对肌肉肉碱转移酶具有高亲和力。它会增加细胞肉碱含量。从而允许游离脂肪酸转运到线粒体中。此外，丙酰-L-肉碱通过为其提供非常容易使用的底物，在缺氧期间刺激克雷布斯循环的更高效率。丙酸盐。无需能量消耗即可快速转化为琥珀酸（回补途径）。鉴于其毒性，丙酸盐不能单独给予患者。慢性心力衰竭患者的 2 期研究结果表明，长期口服丙酰左旋肉碱治疗可比安慰剂改善最大运动持续时间和最大耗氧量，并表明丙酰左旋肉碱对外周肌肉代谢有特定作用。一项对 537 名患者进行的多中心试验表明，丙酰左旋肉碱可以改善心力衰竭患者的运动能力，同时保留心脏功能。
Several experimental studies have shown that levocarnitine reduces myocardial injury after ischemia and reperfusion by counteracting the toxic effect of high levels of free fatty acids, which occur in ischemia, and by improving carbohydrate metabolism. In addition to increasing the rate of fatty acid transport into mitochondria, levocarnitine reduces the intramitochondrial ratio of acetyl-CoA to free CoA, thus stimulating the activity of pyruvate dehydrogenase and increasing the oxidation of pyruvate. Supplementation of the myocardium with levocarnitine results in an increased tissue carnitine content, a prevention of the loss of high-energy phosphate stores, ischemic injury, and improved heart recovery on reperfusion. Clinically, levocarnitine has been shown to have anti-ischemic properties. In small short-term studies, levocarnitine acts as an antianginal agent that reduces, ST segment depression and left ventricular end-diastolic pressure. These short-term studies also show that levocarnitine releases the lactate of coronary artery disease patients subjected to either exercise testing or atrial pacing,. These cardioprotective effects hate been confirmed during aortocoronary bypass grafting and acute myocardial infarction. In a randomized multicenter trial performed on 472 patients, levocarnitine treatment (9 g/day by intravenous infusion for 5 initial days and 6 g/day orally for the next 12 months), when initiated early after acute myocardial infarction, attenuated left ventricular dilatation and prevented ventricular remodeling. In treated patients. there was a trend towards a reduction in the combined incidence of death and CHF after discharge. Levocarnitine could improve ischemia and reperfusion by (1) preventing the accumulation or long-chain acyl-CoA, which facilitates the production or free radicals by damaged mitochondria: (2) improving repair mechanisms for oxidative-induced damage to membrane phospholipids: (3) inhibiting malignancy arrhythmias because of accumulation within the myocardium or long-chain acyl-CoA: and (4) reducing the ischemia-induced apoptosis and the consequent remodeling of the left ventricle. Propionyl-L-carnitine is a carnitine derivative that has a high affinity for muscular carnitine transferase. and it increases cellular carnitine content. thereby allowing free fatty acid transport into the mitochondria. Moreover, propionyl-L-carnitine stimulates a better efficiency of the Krebs cycle during hypoxia by providing it with a very easily usable substrate. propionate. which is rapidly transformed into succinate without energy consumption (anaplerotic pathway). Alone, propionate cannot be administered to patients in view of its toxicity. The results of phase-2 studies in chronic heart failure patients showed that long-term oral treatment with propionyl-L-carnitine improves maximum exercise duration and maximum oxygen consumption over placebo and indicated a specific propionyl-L-carnitine effect on peripheral muscle metabolism. A multicenter trial on 537 patients showed that propionyl-L-carnitine improves exercise capacity in patients with heart failure, but preserved cardiac function.