Yang X P, Samaja M, English E, Benatti P, Tarantola M, Cardace G, Motterlini R, Micheletti R, Bianchi G
Prassis Sigma-Tau Research Institute, University of Milan, Italy.
J Cardiovasc Pharmacol. 1992 Jul;20(1):88-98.
Evidence has been put forth that a number of human and experimental cardiomyopathies are associated with a lower myocardial carnitine content. This study was performed to test the hypothesis that the correction of carnitine derivative, propionyl-L-carnitine (PLC), may improve cardiac function. Repeated administration of PLC was compared to saline with respect to cardiac function in rats with pressure-overload cardiac hypertrophy and low myocardial carnitine levels. Cardiac hypertrophy was induced by abdominal aorta constriction in rats. Separate groups of rats were used for (a) determination of myocardial carnitine content, (b) evaluation of in vivo hemodynamics, and (c) evaluation of performance and metabolic state of Langendorff perfused hearts. Results showed the following: (i) The myocardial carnitine content was inversely correlated to cardiac hypertrophy (r = 0.68, p less than 0.05) and PLC treatment (50 mg/kg i.a. for 4 days) restored it to normal values (ii) The PLC effect on cardiac function was significantly and directly related to cardiac hypertrophy [correlations between heart weight and percent changes in cardiovascular parameters: cardiac output (CO), p less than 0.001; cardiac work (CW), p less than 0.01, stroke volume (SV) and stroke work (SW), p less than 0.02]. In animals with heart weight greater than 1,400 mg, the effect of PLC on CO, CW, SV, SW, and total peripheral resistance (TPR) was significantly different from that of saline (CO, CW, SV, and SW, p less than 0.005 each; TPR, p less than 0.05). The effect was observed 24 h after the first PLC administration and significantly diminished following a 4 day suspension of the treatment. (iii) Perfused hearts from PLC-treated rats displayed a significantly lower left ventricular end-diastolic pressure (p less than 0.01) and greater relaxation rate (p less than 0.05) than those from control rats. Moreover, in PLC-treated hearts, the content of creatine phosphate, ATP, and total adenine nucleotides (ATP+ADP+AMP; TAN) was significantly increased (CP, p less than 0.05; ATP and TAN, p less than 0.01 vs. control). These data show that PLC exerts a stimulatory activity on hearts with hypertrophy and low carnitine content, implying that carnitine deficiency may contribute to the depression of cardiac function in this model.
已有证据表明，许多人类和实验性心肌病与心肌肉碱含量降低有关。本研究旨在验证肉碱衍生物丙酰-L-肉碱（PLC）的纠正可能改善心脏功能这一假设。将PLC重复给药与生理盐水在压力超负荷性心肌肥大且心肌肉碱水平低的大鼠心脏功能方面进行比较。通过大鼠腹主动脉缩窄诱导心肌肥大。将大鼠分为不同组用于：（a）测定心肌肉碱含量；（b）评估体内血流动力学；（c）评估Langendorff灌注心脏的性能和代谢状态。结果如下：（i）心肌肉碱含量与心肌肥大呈负相关（r = 0.68，p < 0.05），PLC治疗（50 mg/kg腹腔注射4天）使其恢复到正常水平；（ii）PLC对心脏功能的影响与心肌肥大显著直接相关[心脏重量与心血管参数百分比变化之间的相关性：心输出量（CO），p < 0.001；心脏作功（CW），p < 0.01，每搏输出量（SV）和每搏作功（SW），p < 0.02]。在心脏重量大于1400 mg的动物中，PLC对CO、CW、SV、SW和总外周阻力（TPR）的影响与生理盐水显著不同（CO、CW、SV和SW，每项p < 0.005；TPR，p < 0.05）。在首次给予PLC后24小时观察到该效应，在治疗暂停4天后显著减弱。（iii）与对照大鼠相比，接受PLC治疗的大鼠的灌注心脏显示左心室舒张末期压力显著降低（p < 0.01），舒张速率更高（p < 0.05）。此外，在接受PLC治疗的心脏中，磷酸肌酸、ATP和总腺嘌呤核苷酸（ATP + ADP + AMP；TAN）的含量显著增加（CP，p < 0.05；ATP和TAN，与对照相比p < 0.01）。这些数据表明，PLC对肥大且肉碱含量低的心脏具有刺激活性，这意味着肉碱缺乏可能导致该模型中心脏功能的抑制。
