Utilization of an isolated, blood-perfused canine papillary muscle preparation as a model to assess efficacy and adversity of class I antiarrhythmic drugs.
Utilization of an isolated, blood-perfused canine papillary muscle preparation as a model to assess efficacy and adversity of class I antiarrhythmic drugs.
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利用分离的、血液灌注的犬乳头肌制剂作为模型来评估 I 类抗心律失常药物的功效和不良反应。
DOI：
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发表时间：
1994
期刊：
影响因子：
--
通讯作者：
K. Hashimoto
中科院分区：
文献类型：
--
作者：
A. Sugiyama;S. Motomura;K. Hashimoto
为了建立一个预测I类抗心律失常药物疗效和不利因素的模型，在与供体狗肝素化血交叉循环的离体犬乳头状肌制剂中，测量了给药后的心室内传导时间（IVCT）、冠状动脉血流量（CBF）、乳头状肌张力（DT）和心室自动性（VR）。河豚毒素、原型快速Na+通道阻滞剂和I类药物增加了IVCT和CBF，但降低了DT和VR，且呈剂量依赖性。已知的一类药物普鲁卡因胺、二丙酰胺、利多卡因、美西汀和氟卡奈的特征相似，但每种药物的效价不同。两种新的一类药物ME3202和AN-132也进行了测试，发现其效果与河豚毒素相似。在我们之前的研究中，延长IVCT 50%的药物剂量与犬抗心律失常血药浓度有很好的相关性。该模型还可用于估计钠通道块的使用依赖性和动力学；然而，它不适合广泛研究细胞和分子机制。因此，该模型的使用有助于比较I类药物的多种心脏作用，可能是更好地评估新型抗心律失常药物的有效方法。
To develop a model to predict the efficacy and adversity of class I antiarrhythmic drugs, intraventricular conduction time (IVCT), coronary blood flow (CBF), developed tension of papillary muscle (DT) and idioventricular automaticity rate (VR) were measured following drug administration in an isolated canine papillary muscle preparation cross-circulated with the heparinized blood of a donor dog. Tetrodotoxin, the prototypic fast Na+ channel blocker, and class I drugs increased IVCT and CBF, but decreased DT and VR, in a dose-dependent manner. The profiles of known class I drugs, procainamide, disopyramide, lidocaine, mexiletine and flecainide were similar, but the potencies of each drug were different. Two new class I drugs, ME3202 and AN-132, were also tested and found to have effects that were similar to that of tetrodotoxin. There was a good correlation between the doses of drugs prolonging IVCT by 50% and the canine antiarrhythmic plasma concentrations in our previous study. This model can also be used to estimate the use-dependency and the kinetics of use-dependent sodium channel block; however, it is not suitable for extensive investigation of cellular and molecular mechanisms. Thus, the use of this model facilitates the comparison of multiple cardiac effects of class I drugs and may be an effective way to better assess new antiarrhythmic drugs.
利多卡因对严重充血性心力衰竭的有害血流动力学影响。
影响因子：
4.8
作者：
Gottlieb,SS;Packer,M
通讯作者：
Packer,M
影响因子：
20.1
作者：
SHEU, SS;LEDERER, WJ
通讯作者：
LEDERER, WJ