Whitmer J T
Circ Res. 1987 Sep;61(3):396-408. doi: 10.1161/01.res.61.3.396.
Hamsters with either the dilated (BIO 53.58) or hypertrophic (BIO 14.6) form of cardiomyopathy and an inbred control strain of hamster (F1B) were treated for 6 months with high-dose L-carnitine (1 g/kg/day i.p.). After treatment, the animals were killed and their hearts perfused by the isolated working technique. Mechanical performance (as indicated by the double product of heart rate and left ventricular [LV] peak systolic pressure) of both carnitine-treated cardiomyopathic groups was increased significantly above their respective sham-treated groups. Associated with these increases in mechanical performance were significant increases in both peak-positive LV dP/dt (index of contractility) and peak negative dP/dt (index of relaxation) in both carnitine-treated myopathic groups. Serum carnitine levels were increased 10-15 times within 2 hours after injection of L-carnitine in all 3 groups. Myocardial free-carnitine levels were increased twofold in both control and dilated myopathic hearts above their respective sham-treated groups, restoring the level in the dilated hearts comparable to those of controls. Myocardial carnitine levels in the hypertrophic group were not significantly affected by treatment. Total high-energy phosphate stores, i.e., ATP plus creatine phosphate, were restored to control levels by L-carnitine treatment in both cardiomyopathic groups. Levels of the breakdown products of ATP were maintained primarily in the more readily convertible adenosine diphosphate and adenosine monophosphate forms in all three treated groups. These changes resulted in significantly higher ratios of (ATP)/(ADP + AMP + adenosine) and (creatine phosphate)/(creatine) in the treated hearts. This is the first study demonstrating that high-dose L-carnitine treatment results in improved cardiac performance and increased myocardial total high-energy phosphate stores in the Syrian hamster model with one of two distinct forms of cardiomyopathy, i.e., dilated or hypertrophic. The mechanisms for these effects of exogenous L-carnitine treatment cannot be totally explained by changes in oxidative energy metabolism.
将患有扩张型（BIO 53.58）或肥厚型（BIO 14.6）心肌病的仓鼠以及近交系对照仓鼠（F1B）用高剂量左旋肉碱（1克/千克/天，腹腔注射）治疗6个月。治疗后，处死动物并采用离体工作技术对其心脏进行灌注。与各自假手术治疗组相比，接受肉碱治疗的两个心肌病组的机械性能（以心率与左心室[LV]收缩压峰值的乘积表示）均显著提高。与这些机械性能的提高相关的是，接受肉碱治疗的两个肌病组的左心室峰值正向dP/dt（收缩性指标）和峰值负向dP/dt（舒张指标）均显著增加。在所有3组中，注射左旋肉碱后2小时内血清肉碱水平增加了10 - 15倍。对照和扩张型肌病心脏中的心肌游离肉碱水平均比各自的假手术治疗组增加了两倍，使扩张型心脏中的水平恢复到与对照组相当的水平。肥厚型组的心肌肉碱水平未受到治疗的显著影响。在两个心肌病组中，左旋肉碱治疗使总高能磷酸储存（即ATP加磷酸肌酸）恢复到对照水平。在所有三个治疗组中，ATP分解产物的水平主要维持在更易转化的二磷酸腺苷和一磷酸腺苷形式。这些变化导致治疗后心脏中（ATP）/（ADP + AMP + 腺苷）和（磷酸肌酸）/（肌酸）的比率显著更高。这是第一项表明高剂量左旋肉碱治疗可改善叙利亚仓鼠模型中两种不同形式心肌病（即扩张型或肥厚型）之一的心脏性能并增加心肌总高能磷酸储存的研究。外源性左旋肉碱治疗这些作用的机制不能完全用氧化能量代谢的变化来解释。
