异常复极作为 Brugada 综合征实验模型中心外膜记录的晚电位和碎裂电图的基础。
Abnormal repolarization as the basis for late potentials and fractionated electrograms recorded from epicardium in experimental models of Brugada syndrome.
机构信息
Masonic Medical Research Laboratory, Utica, New York; Department of Pharmacology and Pharmacotherapy, University of Szeged, Szeged, Hungary.
Masonic Medical Research Laboratory, Utica, New York.
出版信息
J Am Coll Cardiol. 2014 May 20;63(19):2037-45. doi: 10.1016/j.jacc.2014.01.067. Epub 2014 Mar 19.
OBJECTIVES
The aim of this study was to test the hypothesis that late potentials and fractionated electrogram activity are due to delayed depolarization within the anterior aspects of right ventricular (RV) epicardium in experimental models of Brugada syndrome (BrS).
BACKGROUND
Clinical reports have demonstrated late potentials on signal-averaged electrocardiography (ECG) recorded in patients with BrS. Recent studies report the appearance of late potentials and fractionated activity on bipolar electrograms recorded in the epicardium of the RV outflow tract in patients with BrS.
METHODS
Action potential and bipolar electrograms were recorded at epicardial and endocardial sites of coronary-perfused canine RV wedge preparations, together with a pseudo-ECG. The transient outward potassium current agonist NS5806 (5 μM) and the Ca(2+)-channel blocker verapamil (2 μM) were used to pharmacologically mimic the BrS genetic defect.
RESULTS
Fractionated electrical activity was observed in RV epicardium, but not in endocardium, as a consequence of heterogeneities in the appearance of the second upstroke of the epicardial action potential, and discrete high-frequency spikes developed as a result of concealed phase 2 re-entry. In no case did we observe primary conduction delay as the cause of the BrS ECG phenotype or of late potential or fractionated electrogram activity. Quinidine (10 μM) and the phosphodiesterase-3 inhibitors cilostazol (10 μM) and milrinone (2.5 μM) restored electrical homogeneity, thus abolishing all late potentials and fractionated electrical activity.
CONCLUSIONS
These data point to an alternative pathophysiological basis for late potentials and fractionated electrical activity recorded in the right ventricle in the setting of BrS. We demonstrate an association of such activity with abnormal repolarization and not with abnormal depolarization or structural abnormalities.
目的
本研究旨在验证下述假说，即在 Brugada 综合征（BrS）的实验模型中，右心室（RV）心外膜前表面的延迟去极化导致晚期电位和碎裂电图活动。
背景
临床报告表明，BrS 患者的信号平均心电图（ECG）记录中存在晚期电位。最近的研究报告称，BrS 患者 RV 流出道心外膜双极电图上出现晚期电位和碎裂活动。
方法
在冠状灌注犬 RV 楔形标本的心外膜和心内膜部位记录动作电位和双极电图，并记录伪 ECG。使用瞬时外向钾电流激动剂 NS5806（5 μM）和钙通道阻滞剂维拉帕米（2 μM）模拟 BrS 的遗传缺陷。
结果
RV 心外膜出现碎裂电活动，但心内膜没有，这是由于心外膜动作电位第二个上升支出现异质性，以及由于隐匿性 2 相折返而产生离散的高频尖峰。在任何情况下，我们都没有观察到原发性传导延迟是 BrS ECG 表型或晚期电位或碎裂电图活动的原因。奎尼丁（10 μM）和磷酸二酯酶-3 抑制剂西洛他唑（10 μM）和米力农（2.5 μM）恢复了电均一性，从而消除了所有晚期电位和碎裂电活动。
结论
这些数据为 BrS 背景下心外膜 RV 记录的晚期电位和碎裂电活动提供了另一种病理生理学基础。我们证明，这种活动与异常复极有关，而与异常去极化或结构异常无关。
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