Role of cardiac α1-adrenoreceptors for the torsadogenic action of IKr blocker nifekalant in the anesthetized atrioventricular block rabbit
Role of cardiac α1-adrenoreceptors for the torsadogenic action of IKr blocker nifekalant in the anesthetized atrioventricular block rabbit
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心脏 α1 肾上腺素受体在 IKr 阻滞剂尼非卡兰麻醉房室传导阻滞兔子中的扭转作用中的作用
DOI：
10.1016/j.jphs.2022.07.003
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发表时间：
2022
影响因子：
3.5
通讯作者：
Takahara Akira
中科院分区：
文献类型：
--
作者：
Kawakami Satoshi;Kambayashi Ryuichi;Takada Kazuhiro;Aimoto Megumi;Nagasawa Yoshinobu;Takahara Akira
我们分析了心脏α1-肾上腺素受体在异氟烷麻醉的房室传导阻滞兔中 IKr 阻滞剂尼非卡兰的扭转致扭转作用中的作用。通过房室结消融诱导心动过缓，并且在整个实验中以60次/分钟的恒定速率电驱动心室，以防止心室复极相中IKr阻滞剂的速率依赖性改变。尼非卡兰（3 mg/kg 每 10 分钟，n = 5）将单相动作电位 (MAP90) 持续时间延长 +178 ± 43 ms，将复极短期变异性 (STV) 增加至 4.2 ± 1.2 ms，并在 1 只动物中诱发尖端扭转型室性心动过速 (TdP)。在存在甲氧明 (n = 5) 的情况下，尼非卡兰将 MAP90 延长 +328 ± 32 ms，将 STV 增加至 8.0 ± 1.0 ms，并在 2 只动物中诱导 TdP。在哌唑嗪和甲氧明存在的情况下 (n = 5)，尼非卡兰将 MAP90 延长 +267 ± 22 ms，将 STV 增加至 9.2 ± 3.6 ms，并且不诱导 TdP。这些结果表明，甲氧明激活心脏α1-肾上腺素受体本质上使兔心脏对尼非卡兰诱导的QT间期延长敏感，从而导致TdP的发生。
We analyzed role of cardiac α1-adrenoreceptors for the torsadogenic action ofIKrblocker nifekalant in isoflurane-anesthetized atrioventricular block rabbits. Bradycardia was induced by atrioventricular node ablation, and the ventricle was electrically driven at a constant rate of 60 beats/min throughout the experiments to prevent rate-dependent modification by theIKrblocker in ventricular repolarization phase. Nifekalant (3 mg/kg per 10 min, n = 5) prolonged the duration of monophasic action potential (MAP90) by +178 ± 43 ms, increased the short-term variability of repolarization (STV) to 4.2 ± 1.2 ms, and induced torsade de pointes (TdP) in 1 animal. In the presence of methoxamine (n = 5), nifekalant prolonged the MAP90by +328 ± 32 ms, increased the STV to 8.0 ± 1.0 ms, and induced TdP in 2 animals. In the presence of prazosin and methoxamine (n = 5), nifekalant prolonged the MAP90by +267 ± 22 ms, increased the STV to 9.2 ± 3.6 ms, and induced no TdP. These results suggest that cardiac α1-adrenoreceptor activation by methoxamine essentially sensitizes the rabbit heart to nifekalant-induced QT interval prolongation, leading to the onset of TdP.