Anand I, Chandrashekhan Y, De Giuli F, Pasini E, Mazzoletti A, Confortini R, Ferrari R
VA Medical Center, Minneapolis, Minnesota, USA.
Cardiovasc Drugs Ther. 1998 Jul;12(3):291-9. doi: 10.1023/a:1007721917561.
Carnitine is an important cofactor in the intermediary metabolism of the heart, and carnitine deficiency is associated with congestive heart failure. We therefore studied the effects of acute (IV bolus, 30 mg/kg body weight) and chronic administration (1.5 mg/d for 1 month) of propionyl-L-carnitine on hemodynamics, hormone levels, ventricular function, exercise capacity, and peak oxygen consumption in 30 patients with chronic congestive heart failure (NYHA II-III, mean EF 29.5 +/- 7%) in a phase II, parallel, single-blind, randomized, and placebo-controlled study. Acute administration of propionyl-L-carnitine caused a significant reduction in pulmonary artery and pulmonary wedge pressures at both day 1 (P < 0.001) and day 30 (P < 0.05) of the study but no other hemodynamics changes. Hormone levels did not change following acute administration of the drug. Chronic administration of propionyl-L-carnitine increased peak oxygen consumption by 45% (from 16.0 +/- 3 to 23.5 +/- 2 mL/kg/min, P +/- 0.001), exercise time by 21% (from 8.1 +/- 0.5 to 9.8 +/- 0.4 minutes, P < 0.01), and peak exercise heart rate by 12% (P < 0.01). These changes were concomitant with a reduction of pulmonary artery pressure. In the treated group, there was a slight, but significant (P < 0.01), reduction in left ventricular dimensions. Hemodynamics and hormones measured after 1 month of oral therapy remained unchanged, except for a fall in pulmonary artery pressures, with a nonsignificant trend towards a fall in filling pressures and plasma norepinephrine. The chronic changes in the propionyl-L-carnitine group were seen at 15 days of treatment, and no further changes in these parameters were seen at 1 month. We conclude that propionyl-L-carnitine increases exercise capacity and reduces ventricular size in patients with congestive heart failure. The drug has no significant effects on hemodynamics or neurohormone levels. The use of a single-blind design reduces the impact of the positive finding on exercise capacity.
肉碱是心脏中间代谢的重要辅助因子，肉碱缺乏与充血性心力衰竭相关。因此，我们在一项II期、平行、单盲、随机、安慰剂对照研究中，研究了丙酰-L-肉碱急性（静脉推注，30mg/kg体重）和慢性给药（1.5mg/d，持续1个月）对30例慢性充血性心力衰竭患者（纽约心脏协会II-III级，平均射血分数29.5±7%）的血流动力学、激素水平、心室功能、运动能力和峰值耗氧量的影响。丙酰-L-肉碱急性给药在研究的第1天（P<0.001）和第30天（P<0.05）均导致肺动脉压和肺楔压显著降低，但无其他血流动力学变化。药物急性给药后激素水平未改变。丙酰-L-肉碱慢性给药使峰值耗氧量增加45%（从16.0±3增加到23.5±2ml/kg/min，P±0.001），运动时间增加21%（从8.1±0.5增加到9.8±0.4分钟，P<0.01），运动峰值心率增加12%（P<0.01）。这些变化与肺动脉压降低同时出现。在治疗组中，左心室尺寸有轻微但显著的减小（P<0.01）。口服治疗1个月后测量的血流动力学和激素水平保持不变，除了肺动脉压下降，充盈压和血浆去甲肾上腺素下降趋势不显著。丙酰-L-肉碱组的慢性变化在治疗15天时出现，1个月时这些参数无进一步变化。我们得出结论，丙酰-L-肉碱可增加充血性心力衰竭患者的运动能力并减小心室大小。该药物对血流动力学或神经激素水平无显著影响。采用单盲设计减少了阳性结果对运动能力的影响。
