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麻醉大鼠冠状动脉结扎-再灌注心律失常模型及离体灌注大鼠心脏中利多卡因的浓度-效应关系

Coronary ligation-reperfusion arrhythmia models in anesthetized rats and isolated perfused rat hearts concentration-effect relationships of lidocaine.

作者信息

Uematsu T, Vozeh S, Ha H R, Hof R P, Follath F

出版信息

J Pharmacol Methods. 1986 Aug;16(1):53-61. doi: 10.1016/0160-5402(86)90028-8.

Abstract

A comparative study of two arrhythmia models was carried out using coronary ligation and reperfusion in anesthetized rats and in isolated rat hearts. Both models allowed evaluation of the concentration-effect relationships of lidocaine as an antiarrhythmic agent. The average free plasma-water concentration that reduced the incidence of ventricular fibrillation by 50% was comparable in both models: 1.9 mg/liter in vivo and 2.1 mg/liter in vitro, respectively. In isolated rat hearts significantly higher concentrations were required for 50% reduction of ventricular tachycardia than for the suppression of ventricular fibrillation (2.9 +/- 0.13 versus 2.1 +/- 0.11 mg/liter, p less than 0.05). The good agreement between effective lidocaine concentrations in vivo and in vitro suggests that the isolated rat heart preparation is suitable for the quantitative assessment of drug effects on occlusion-reperfusion arrhythmias. A better reproducibility and easier control of drug concentrations are the advantages of the in vitro model.

摘要

在麻醉大鼠和离体大鼠心脏中,采用冠状动脉结扎和再灌注的方法对两种心律失常模型进行了比较研究。两种模型均能评估利多卡因作为抗心律失常药物的浓度-效应关系。两种模型中使室颤发生率降低50%的平均游离血浆-水浓度相当:体内为1.9毫克/升,体外为2.1毫克/升。在离体大鼠心脏中,使室性心动过速发生率降低50%所需的浓度显著高于抑制室颤所需的浓度(2.9±0.13对2.1±0.11毫克/升,p<0.05)。体内和体外利多卡因有效浓度之间的良好一致性表明,离体大鼠心脏制备方法适用于定量评估药物对闭塞-再灌注心律失常的影响。体外模型的优点是重现性更好且更容易控制药物浓度。

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