Bartels G L, Remme W J, Holwerda K J, Kruijssen D A
Sticares, Cardiovascular Research Foundation, Rotterdam, The Netherlands.
Eur Heart J. 1996 Mar;17(3):414-20. doi: 10.1093/oxfordjournals.eurheartj.a014874.
L-propionylcarnitine, a naturally occurring derivative of L-carnitine, essential for mitochondrial fatty acid transport and high-energy phosphate exchange, acutely reduces myocardial ischaemia and improves ischaemia-induced cardiac dysfunction following intravenous administration. This randomized, crossover study was designed to compare the long-term anti-ischaemic effects of oral L-propionylcarnitine with diltiazem in patients with stable, exercise-induced angina. After a 2-week washout phase of anti-anginal medication and a 2-week single-blind placebo period, 46 patients were included in the study, 23 of whom received 1500 mg L-propionylcarnitine daily for 6 weeks, and 23 diltiazem (180 mg daily for 3 weeks, followed by 360 mg daily for 3 weeks), crossing over to the other treatment after a 1-week washout period. Three patients on L-propionylcarnitine and two on diltiazem discontinued. Both treatments resulted in comparable exercise duration (582 +/- 35 s and 588 +/- 33 s, mean +/- SEM), time to 0.1 mV ST depression (436 +/- 38 s and 465 +/- 36 s), and increase in time to 0.1 mV ST depression from baseline (20% and 28%), L-propionylcarnitine and diltiazem, respectively. Diltiazem decreased the rate-pressure product at rest and exercise, L-propionylcarnitine did not. Both compounds significantly reduced ST depression at maximal exercise [23% (L-propionylcarnitine) vs 35% (diltiazem), P < 0.05 diltiazem vs L-propionylcarnitine]. Diltiazem increased the time to onset of angina by 22%. In contrast, no significant changes occurred with L-propionylcarnitine. During the study, anginal attacks were reduced by 70% and 57%, and nitroglycerin consumption decreased by 57% and 70%, L-propionylcarnitine and diltiazem, respectively. Thus, both L-propionylcarnitine and (high-dose) diltiazem result in anti-ischaemic effects and decrease anginal attacks in daily life. Although the effect of diltiazem on exercise-induced ischaemia appears more pronounced than that of L-propionylcarnitine, this novel metabolic approach to ischaemia warrants further development.
L-丙酰肉碱是L-肉碱的一种天然衍生物，对线粒体脂肪酸转运和高能磷酸交换至关重要，静脉给药后可急性减轻心肌缺血并改善缺血诱导的心脏功能障碍。这项随机交叉研究旨在比较口服L-丙酰肉碱与地尔硫䓬对稳定型运动诱发心绞痛患者的长期抗缺血作用。在经过2周的抗心绞痛药物洗脱期和2周的单盲安慰剂期后，46例患者被纳入研究，其中23例患者每天服用1500mg L-丙酰肉碱，持续6周，另外23例患者服用地尔硫䓬（前3周每天180mg，后3周每天360mg），在1周的洗脱期后交叉接受另一种治疗。3例服用L-丙酰肉碱的患者和2例服用地尔硫䓬的患者停药。两种治疗导致的运动持续时间（分别为582±35秒和588±33秒，平均值±标准误）、出现0.1mV ST段压低的时间（分别为436±38秒和465±36秒）以及与基线相比出现0.1mV ST段压低的时间增加幅度（分别为20%和28%）相当，分别为L-丙酰肉碱和地尔硫䓬。地尔硫䓬可降低静息和运动时的心率-血压乘积，L-丙酰肉碱则无此作用。两种化合物均显著降低最大运动时的ST段压低[L-丙酰肉碱为23%，地尔硫䓬为35%，地尔硫䓬与L-丙酰肉碱相比，P<0.05]。地尔硫䓬使心绞痛发作时间延长22%。相比之下，L-丙酰肉碱未出现显著变化。在研究期间，L-丙酰肉碱和地尔硫䓬分别使心绞痛发作减少70%和57%，硝酸甘油消耗量分别减少57%和70%。因此，L-丙酰肉碱和（高剂量）地尔硫䓬均产生抗缺血作用并减少日常生活中的心绞痛发作。尽管地尔硫䓬对运动诱发缺血的作用似乎比L-丙酰肉碱更显著，但这种针对缺血的新型代谢方法值得进一步研究。
