Arrhythmogenic activities of antiarrhythmic drugs in conscious hypokalemic dogs with atrioventricular block: comparison between quinidine, lidocaine, flecainide, propranolol and sotalol.
Arrhythmogenic activities of antiarrhythmic drugs in conscious hypokalemic dogs with atrioventricular block: comparison between quinidine, lidocaine, flecainide, propranolol and sotalol.
复制标题
抗心律失常药物对伴有房室传导阻滞的清醒低钾犬的致心律失常活性：奎尼丁、利多卡因、氟卡尼、普萘洛尔和索他洛尔之间的比较。
DOI：
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发表时间：
1991
影响因子：
3.5
通讯作者：
G. Cheymol
中科院分区：
文献类型：
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作者：
J. Weissenburger;J. Davy;F. Chézalviel;O. Ertzbischoff;J. Poirier;F. Engel;P. Lainée;E. Penin;G. Motté;G. Cheymol
为了建立和评价一个对药物的QT依赖性促心律失常作用敏感的模型，在具有心动过缓和低钾血症的慢性仪器狗中产生长QT综合征。心动过缓（平均周期长度：1495 +/- 78 msec）由永久性房室传导阻滞和高剂量利尿剂引起的低钾血症（K+ = 2.6 +/- 0.05 mmol/l）提供。为了评估该模型，对其中6只清醒的犬进行奎尼丁、氟卡尼、利多卡因、普萘洛尔和索他洛尔输注。在交叉设计中，在实验期间以允许稳定和无毒药物血浆水平的速率静脉输注药物。在输注开始前30分钟（基线）和输注开始后75分钟记录四导联ECG的心律失常。索他洛尔、利多卡因和普萘洛尔显著增加心室周期长度（分别为+618 +/- 192、+388 +/- 125和+329 +/- 114 msec），索他洛尔、奎尼丁和氟卡尼增加QT间期（分别为+56 +/- 8、+31 +/- 7.9和+20 +/- 5.7 msec）。奎尼丁和索他洛尔，而不是氟卡尼，普萘洛尔或利多卡因，表现出显着的促肾上腺皮质激素活性。在奎尼丁输注期间，大多数犬表现出一些室性心律失常，最严重的形式是室性心动过速。这些心律失常被高频率起搏抑制。在索他洛尔输注期间，6只犬中有5只表现出典型的“尖端扭转型室性心动过速”。“这种发生率与索他洛尔对心室自主起搏器的减慢作用无关，因为在5只以40 bpm起搏的互补犬中获得了类似的发生率。这可能与剂量有关，因为在接受对照研究中使用的一半剂量的另一组5只犬中仅发生1次尖端扭转型室性心动过速。只有奎尼丁和索他洛尔与尖端扭转型室性心动过速临床相关，而普萘洛尔、氟卡尼或利多卡因与尖端扭转型室性心动过速无关。它们也是本研究中唯一与促心律失常事件相关的药物，这一事实表明，在完全房室传导阻滞的清醒低钾血症犬中，可以可靠地评价药物的QT依赖性促心律失常作用。
In order to create and evaluate a model sensitive to QT-dependent proarrhythmic effects of drugs, a long QT syndrome was produced in chronically instrumented dogs with bradycardia and hypokalemia. Bradycardia (mean cycle length: 1495 +/- 78 msec) was provided by permanent atrioventricular block and hypokalemia (K+ = 2.6 +/- 0.05 mmol/l) by high doses of diuretics. To evaluate that model, six of these conscious dogs were subjected to quinidine, flecainide, lidocaine, propranolol and sotalol infusions. In crossover design, drugs were infused i.v. at rates allowing stable and nontoxic drug plasma levels during the experiment. Four-lead ECGs were recorded for arrhythmias for 30 min before (base line) and 75 min after onset of infusion. Ventricular cycle length was increased dramatically by sotalol, lidocaine and propranolol (+618 +/- 192, +388 +/- 125 and +329 +/- 114 msec, respectively) and QT interval was increased by sotalol, quinidine and flecainide (+56 +/- 8, +31 +/- 7.9 and +20 +/- 5.7 msec, respectively). Quinidine and sotalol, but not flecainide, propranolol or lidocaine, exhibited significant arrhythmogenic activities. During quinidine infusion, most dogs exhibited some ventricular arrhythmias whose most severe forms were runs of ventricular tachycardia. These arrhythmias were suppressed by pacing at high rates. During sotalol infusion, five out of six dogs exhibited typical "torsades de pointes." This incidence was not related to the slowing effects of sotalol on idioventricular pacemakers, because a similar incidence was obtained in five complementary dogs paced at 40 bpm. It could be related to dose, because torsades de pointes occurred only once in another group of five dogs receiving half the dose used in the controlled study. Only quinidine and sotalol, but not propranolol, flecainide or lidocaine, are clinically associated to torsades de pointes. They were also the only drugs associated with proarrhythmic events in the present study, a fact suggesting that QT-dependent arrhythmogenic effects of drugs can be reliably evaluated in conscious hypokalemic dogs with complete atrioventricular block.