Role of sodium and calcium channel block in unmasking the Brugada syndrome
Role of sodium and calcium channel block in unmasking the Brugada syndrome
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DOI：
10.1016/j.hrthm.2004.03.061
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发表时间：
2004-07-01
期刊：
影响因子：
5.5
通讯作者：
Antzelevitch, C
中科院分区：
文献类型：
--
作者：
Fish, JM;Antzelevitch, C
目的：我们假设I-Na和I-Ca联合阻断可能更有效地引起心外膜动作电位（AP）圆顶的丧失和诱发Brugada综合征（BS）。本研究的目的是测试这一假设在体外模型的BS。背景Brugada综合征的特点是ST段抬高的右胸导联心电图和猝死的高风险。BS的ECG体征通常被掩盖，但可以通过强效钠通道阻滞剂被揭露。采用犬右心室（RV）楔形标本，用氟卡尼抑制RV心外膜AP圆顶，建立了BS的实验模型。方法在犬RV楔形标本上同时记录细胞内AP和透壁ECG。（5-10 μ M）诱导的I-Ca和I-Na阻滞引起心外膜AP圆顶的不均匀损失，导致ST段抬高，2相折返（12/16），自发性多形性室速/室颤（6/16）。氟卡尼（小于或等于7.5 μ M）、阿替卡韦（小于或等于20 μ M）和普鲁卡因胺（小于或等于300 μ M）在任何制剂中都不能产生多晶型VT，除非与钙通道阻滞剂（维拉帕米，小于或等于20 μ M）联合使用。特非那定诱导的ST段抬高正常化和心律失常抑制以下It. block与4-aminopyridine（0.5-2 mM）。结论我们的数据表明，联合钠和钙通道阻滞可能是更有效的比钠通道阻滞单独在揭露Brugada综合征和药理学药物，抑制I-to可能是有用的，在预防致命的心律失常综合征患者。(C)2004心脏节律学会。All rights reserved.
OBJECTIVE We hypothesized that a combination of I-Na and I-Ca blockade may be more effective in causing loss of the epicardial action potential (AP) dome and precipitating the Brugada syndrome (BS). The present study was designed to test this hypothesis in an in vitro model of BS.BACKGROUND The Brugada syndrome is characterized by an ST segment elevation in the right precordial ECG leads and a high risk of sudden death. The ECG sign of BS is often concealed, but can be unmasked with potent sodium channel blockers. Using canine right ventricular (RV) wedge preparations, we previously developed an experimental model of BS using flecainide to depress the AP dome in RV epicardium.METHODS Intracellular APs and a transmural ECG were simultaneously recorded from canine RV wedge preparations.RESULTS Terfenadine (5-10 muM)-induced block of I-Ca and I-Na caused heterogeneous loss of the epicardial AP dome, resulting in ST segment elevation, phase 2 reentry (12/16), and spontaneous polymorphic VT/VF (6/16). Flecainide (less than or equal to7.5 muM), ajmaline (less than or equal to20 muM), and procainamide (less than or equal to300 muM) failed to generate polymorphic VT in any preparation except when combined with a calcium channel blocker (verapamil, less than or equal to20 muM). Terfenadine-induced ST segment elevation was normalized and arrhythmias suppressed following It. block with 4-aminopyridine (0.5-2 mM).CONCLUSION Our data suggest that combined sodium and calcium channel block may be more effective than sodium channel block alone in unmasking the Brugada syndrome and that pharmacologic agents that inhibit I-to may be useful in preventing lethal arrhythmias in patients with the syndrome. (C) 2004 Heart Rhythm Society. All rights reserved.