Krejcy K, Krumpl G, Todt H, Raberger G
Department of Cardiovascular Pharmacology, University of Vienna, Austria.
Naunyn Schmiedebergs Arch Pharmacol. 1992 Aug;346(2):213-8. doi: 10.1007/BF00165304.
The aim of the present study was to investigate the dose-dependent antiarrhythmic efficacy of lidocaine against electrically induced tachycardias in conscious, chronically instrumented postinfarction dogs. Programmed electrical stimulation (PES) was performed in 16 dogs 8 to 21 days after a 4 h occlusion of the left anterior descending coronary artery (LAD). Infusion of saline in 8 control animals with sustained ventricular tachycardia (SVT) inducible at baseline did not affect subsequent inducibility. In the treatment group 7 of 8 animals responded with SVT and one exhibited ventricular fibrillation at baseline. After an initial bolus of 1 mg/kg lidocaine intravenously (i.v.), the drug was infused at infusion rates of 40, 80 and 120 micrograms/kg/min (i.v.). During 80 micrograms/kg/min lidocaine (mean plasma level 3.5 micrograms/ml) 7 out of 8 animals displayed an antiarrhythmic response; both the lower and the higher infusion rate were associated with a smaller antiarrhythmic efficacy (3 of 8 animals responded to 40 micrograms/kg/min and 4 of 8 to 120 micrograms/kg/min). Licocaine did not affect ventricular refractory periods, but induced an increase in intraventricular conduction time at all infusion rates, from 66.2 ms at baseline to 67.7 ms (p less than 0.05), 67.7 ms (p less than 0.05), 70.0 ms (p less than 0.01) respectively. In conclusion the present study demonstrates that lidocaine is of considerable value in the management of PES-induced ventricular arrhythmias in the postinfarction phase. However there is only a small optimal therapeutic plasma level range, where lidocaine exhibits its antiarrhythmic efficacy against this type of arrhythmia; this makes a carefully titration of the drug necessary both in the experimental and in the clinical setting.
本研究的目的是探讨利多卡因对清醒、长期植入仪器的心肌梗死后犬电诱导心动过速的剂量依赖性抗心律失常疗效。在左冠状动脉前降支(LAD)闭塞4小时后8至21天,对16只犬进行程控电刺激(PES)。8只基线时可诱导持续性室性心动过速(SVT)的对照动物输注生理盐水,不影响随后的可诱导性。治疗组8只动物中有7只在基线时出现SVT,1只出现室颤。静脉注射1mg/kg利多卡因初始推注后,以40、80和120μg/kg/min(静脉注射)的输注速率输注该药物。在80μg/kg/min利多卡因输注期间(平均血浆水平3.5μg/ml),8只动物中有7只表现出抗心律失常反应;较低和较高的输注速率均与较小的抗心律失常疗效相关(8只动物中有3只对40μg/kg/min有反应,8只中有4只对120μg/kg/min有反应)。利多卡因不影响心室不应期,但在所有输注速率下均导致室内传导时间增加,从基线时的66.2ms分别增加到67.7ms(p<0.05)、67.7ms(p<0.05)、70.0ms(p<0.01)。总之,本研究表明利多卡因在心肌梗死后阶段处理PES诱导的室性心律失常方面具有重要价值。然而,只有一个很小的最佳治疗血浆水平范围,利多卡因在此范围内对这种类型的心律失常表现出抗心律失常疗效;这使得在实验和临床环境中都必须仔细滴定药物。