Autonomic and cellular mechanisms mediating detrimental cardiac effects of status epilepticus.
Autonomic and cellular mechanisms mediating detrimental cardiac effects of status epilepticus.
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DOI：
10.1016/j.eplepsyres.2010.06.013
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发表时间：
2010-09
影响因子：
2.2
通讯作者：
Anderson, Anne E.
中科院分区：
文献类型：
--
作者：
Bealer, Steven L.;Little, Jason G.;Metcalf, Cameron S.;Brewster, Amy L.;Anderson, Anne E.
长时间的癫痫发作（癫痫持续状态；SE）可导致癫痫发作终止后较长一段时间内对致命性室性心律失常的易感性增加。 SE 伴随着交感神经系统 (SymNS) 的急性、强烈激活，导致肌细胞肌丝损伤、心电活动发生致心律失常改变以及室性心律失常的易感性增加。然而，介导心脏功能变化的机制以及 SE 期间产生的特定致心律失常底物尚不清楚。为了确定SE对心脏的有害影响是否是由SymNS刺激心脏介导的，我们检查了癫痫发作期间B-肾上腺素能阻滞剂（阿替洛尔）对血压、心率、肌细胞肌丝损伤（心肌肌钙蛋白I，cTnI）、心电图活动和心律失常易感性的影响。此外，我们确定 SE 是否与 Kv4.x 钾通道表达的改变有关，Kv4.x 钾通道对于动作电位复极化至关重要，从而对正常心电活动有显着贡献。锂-毛果芸香碱诱导的 SE 与急性心动过速、高血压和心肌细胞损伤有关。 SE 后的前 2 周内，心电活动的致心律失常改变伴随着对实验诱发心律失常的敏感性增加是明显的。癫痫发作期间阿替洛尔治疗可以预防这两种情况。此外，SE 后 1 周和两周，心肌细胞离子通道重塑很明显，其特征是心脏 Kv4.2 钾通道表达减少。这些数据表明，SE 期间长时间和强烈的 SymNS 激活对心脏的影响会导致肌丝损伤和 Kv4.2 通道下调，从而改变心脏电活动并增加对致命性心律失常的易感性。
Prolonged seizure activity (status epilepticus; SE) can result in increased susceptibility to lethal ventricular arrhythmias for an extended period of time following seizure termination. SE is accompanied by acute, intense activation of the sympathetic nervous system (SymNS) and results in myocyte myofilament damage, arrhythmogenic alterations in cardiac electrical activity, and increased susceptibility to ventricular arrhythmias. However, the mechanisms mediating the changes in cardiac function, and the specific arrhythmogenic substrate produced during SE are unknown. To determine if detrimental cardiac effects of SE are mediated by SymNS stimulation of the heart, we examined the effects of B-adrenergic blockade (atenolol) during seizure activity on blood pressure, heart rate, myocyte myofilament injury (cardiac troponin I, cTnI), electrocardiographic activity, and susceptibility to arrhythmias. Furthermore, we determined if SE was associated with altered expression of the Kv4.x potassium channels, which are critical for action potential repolarization and thereby contribute significantly to normal cardiac electrical activity. Lithium-pilocarpine induced SE was associated with acute tachycardia, hypertension, and cardiomyocyte damage. Arrhythmogenic alterations in cardiac electrical activity accompanied by increased susceptibility to experimentally induced arrhythmias were evident during the first 2 wks following SE. Both were prevented by atenolol treatment during seizures. Furthermore, one and two weeks after SE, myocyte ion channel remodeling, characterized by a decreased expression of cardiac Kv4.2 potassium channels, was evident. These data suggest that the cardiac effects of prolonged and intense SymNS activation during SE induce myofilament damage and downregulation of Kv4.2 channels, which alter cardiac electrical activity and increase susceptibility to lethal arrhythmias.
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影响因子：
11.2
作者：
Johnston, SC;Siedenberg, R;Laxer, KD
通讯作者：
Laxer, KD
影响因子：
2.4
作者：
Kurata, Masaaki;Iidaka, Takeshi;Shirai, Norimitsu
通讯作者：
Shirai, Norimitsu
影响因子：
20.1
作者：
Kassiri, Z;Zobel, C;Backx, PH
通讯作者：
Backx, PH
影响因子：
2.2
作者：
Glien, M;Brandt, C;Löscher, W
通讯作者：
Löscher, W
影响因子：
5
作者：
De Sarro, G;Di Paola, ED;Fischer, W
通讯作者：
Fischer, W