Kirimoto T, Morikawa Y, Yamada H, Fujisawa S, Hironaka Y
Earth Chemical Co., Ltd., Hyogo, Japan.
Nihon Yakurigaku Zasshi. 1989 Mar;93(3):155-69. doi: 10.1254/fpj.93.155.
The cardiovascular effects of levocarnitine chloride (LC-80) were investigated in in vitro and in vivo experiments, and the following results were obtained: (1) In isolated rabbit cardiac muscle preparations, LC-80 at the high concentration of 10(-2) M had little influence on the atrial rate of spontaneously beating right atria, while it caused a gradual increase in the contractile tension of both spontaneously beating right atria and electrically driven papillary muscle that reached a maximum level after 10 min of administration and lasted for 20-30 min. However, the LC-80-induced positive inotropic effect may be negligible in whole animal experiments or clinical trials, since it was elicited only after the administration of LC-80 in an extremely large dose. Furthermore, LC-80 in a high concentration (10(-2) M) had no influence on the isoproterenol-induced positive inotropic effect in electrically driven papillary muscles. (2) LC-80 in high concentrations of 10(-3)-10(-2) M did not affect the high K+-induced contraction in isolated canine left circumflex coronary artery and saphenous vein. (3) In anesthetized dogs, intraarterial injection of LC-80 in high doses of up to 10 mg did not change the blood flow of coronary, femoral, renal, mesenteric or vertebral arteries and on the adenosine-induced vasodilator action. (4) In anesthetized dogs, intravenous injection of LC-80 in doses of 100-300 mg/kg did not modify the blood pressure responses induced by norepinephrine, acetylcholine, carotid occlusion and vagal stimulation. These results suggest that the cardiovascular effects of LC-80 are extremely mild or negligible. Therefore, LC-80 may be a drug having a new pharmacological feature in its mechanism which enables it to exert a beneficial effect in the treatment of ischemic heart disease, being different from the commonly used antianginal drugs.
在体外和体内实验中研究了氯化左旋肉碱(LC - 80)的心血管效应,获得了以下结果:(1)在离体兔心肌制备物中,高浓度10⁻² M的LC - 80对自发搏动的右心房的心房率影响很小,而它使自发搏动的右心房和电驱动乳头肌的收缩张力逐渐增加,给药10分钟后达到最大水平,并持续20 - 30分钟。然而,LC - 80诱导的正性肌力作用在全动物实验或临床试验中可能微不足道,因为它仅在给予极大剂量的LC - 80后才出现。此外,高浓度(10⁻² M)的LC - 80对电驱动乳头肌中异丙肾上腺素诱导的正性肌力作用没有影响。(2)高浓度10⁻³ - 10⁻² M的LC - 80不影响离体犬左旋冠状动脉和隐静脉中高钾诱导的收缩。(3)在麻醉犬中,动脉内注射高达10 mg的高剂量LC - 80不会改变冠状动脉、股动脉、肾动脉、肠系膜动脉或椎动脉的血流以及腺苷诱导的血管舒张作用。(4)在麻醉犬中,静脉注射100 - 300 mg/kg剂量的LC - 80不会改变去甲肾上腺素、乙酰胆碱、颈动脉闭塞和迷走神经刺激诱导的血压反应。这些结果表明LC - 80的心血管效应极其轻微或可忽略不计。因此,LC - 80可能是一种在作用机制上具有新药理学特征的药物,使其能够在缺血性心脏病治疗中发挥有益作用,这与常用的抗心绞痛药物不同。