Mechanisms for vagal modulation of ventricular repolarization and of coronary occlusion-induced lethal arrhythmias in cats.
Mechanisms for vagal modulation of ventricular repolarization and of coronary occlusion-induced lethal arrhythmias in cats.
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DOI：
10.1161/01.res.75.4.722
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发表时间：
1994-10
影响因子：
20.1
通讯作者：
L. Rosenshtraukh;P. Danilo;E. Anyukhovsky;S. Steinberg;V. Rybin;K. Brittain-Valenti;V. Molina-Viamonte;M. Rosen
中科院分区：
文献类型：
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作者：
L. Rosenshtraukh;P. Danilo;E. Anyukhovsky;S. Steinberg;V. Rybin;K. Brittain-Valenti;V. Molina-Viamonte;M. Rosen
我们的目标是更好地了解在体内心室毒蕈碱受体的作用机制。因此，我们研究了迷走神经刺激对心室复极和迷走神经张力对麻醉猫左冠状动脉前降支结扎30分钟引起的致死性心律失常的影响。实验组包括正常对照猫只冠状动脉结扎和猫预处理阿托品，百日咳毒素（PTX），或普萘洛尔。所有猫均接受双侧颈部迷走神经刺激（Vstim），频率为1、3和5 Hz，持续1分钟，间隔10分钟。冠脉结扎前，Vstim减慢窦性心率，延长PR间期，降低血压。从电生理功能的角度来看，最重要的是起搏和非起搏心脏中迷走神经诱导的心室复极加速，这可以通过乙酰胆碱的作用（即缩短心外膜下肌肉动作电位）来解释。对复极的影响被阿托品或PTX阻断，但不被普萘洛尔阻断。复极化的窦性减慢和加速程度与功能性PTX敏感性G蛋白水平直接相关（P <0.05）。在心房起搏期间进行冠状动脉闭塞，使所有组的心率相等。对照组室颤发生率为10%，阿托品组和PTX组分别为50%和54%（P <0.05）。冠状动脉闭塞前心房起搏期间，迷走神经指数计算为Vstim期间QTc缩短百分比。迷走神经指数在13%~ 26%时，封堵过程中VF的发生率为零。迷走指数为0%~ 12%时，VF为52%（P <0.01）。结论如下：（1）Vstim通过包含PTX敏感性G蛋白并涉及心外膜和心内膜之间梯度改变的途径加速猫的心室复极。(2)在缺血期间迷走神经张力的去除有利于VF，正如迷走神经指数所预测的那样。
Our goal was to better understand the mechanisms underlying muscarinic receptor actions on the ventricle in vivo. Therefore, we studied the effects of vagal stimulation on ventricular repolarization and of vagal tone on lethal arrhythmias induced by 30 minutes of left anterior descending coronary artery ligation in anesthetized cats. Experimental groups included normal control cats subjected only to coronary ligation and cats pretreated with atropine, pertussis toxin (PTX), or propranolol. All cats received bilateral cervical vagal stimulation (Vstim) at 1, 3, and 5 Hz for 1 minute at 10-minute intervals. Before coronary ligation, Vstim slowed sinus rate, prolonged the PR interval, and lowered blood pressure. Most important from the point of view of electrophysiological function was a vagally induced acceleration of ventricular repolarization in paced and unpaced hearts, which could be explained by the effects of acetylcholine (ie, shortening the subepicardial muscle action potentials). The effect on repolarization was blocked by atropine or PTX but not by propranolol. The extent of sinus slowing and acceleration of repolarization was directly related to the level of functional PTX-sensitive G protein (P < .05). Coronary occlusion was performed during atrial pacing such that the heart rate in all groups was equal. The incidence of ventricular fibrillation (VF) was 10% in the control group and 50% and 54% in atropine and PTX groups, respectively (P < .05). During atrial pacing before coronary occlusion, a vagal index was calculated as percent QTc shortening during Vstim. When the vagal index was 13% to 26%, the incidence of VF during occlusion was zero. When the vagal index was 0% to 12%, VF was 52% (P < .01). Conclusions are as follows: (1) Vstim accelerates ventricular repolarization in cats via a pathway that incorporates a PTX-sensitive G protein and involves an altered gradient between epicardium and endocardium. (2) Removal of vagal tone during ischemia favors VF, as predicted by a vagal index.