Cellular basis for the Brugada syndrome and other mechanisms of arrhythmogenesis associated with ST-segment elevation
Cellular basis for the Brugada syndrome and other mechanisms of arrhythmogenesis associated with ST-segment elevation
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DOI：
10.1161/01.cir.100.15.1660
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发表时间：
1999-10-12
期刊：
影响因子：
37.8
通讯作者：
Antzelevitch, C
中科院分区：
文献类型：
--
作者：
Yan, GX;Antzelevitch, C
背景：Brugada综合征的特点是右心前心电图导联st段明显抬高，与突发性和非预期的心律失常死亡的高发相关。我们的研究考察了这种综合征的细胞基础。方法与结果：利用动脉灌注的犬右心室楔形，同时记录2个心外膜和1个心内膜部位的跨膜动作电位，以及单极电图和跨壁EGG。暴露于pinacidil （2 ~ 5 mu mol/L）、K+通道开启剂或Na+通道阻滞剂（flecainide, 7 mu mol/L）和乙酰胆碱（ACh, 2 ~ 3 mu mol/L）后，心外膜动作电位穹幕的丧失而不是心内膜动作电位穹幕的丧失，导致心外膜反应缩短和复极的跨壁弥散，从而引起心电图st段抬高。乙酰胆碱促进动作电位穹丘的丢失，而异丙肾上腺素（0.1 ~ 1 μ mol/L）恢复心外膜穹丘，从而降低或消除st段抬高。圆顶的不均匀丢失引起心外膜和跨壁内复极的明显分散，从而引起第2期再入性心动过速。用4-氨基吡啶（1 ~ 2 mmol/L）或奎尼丁（5 mu mol/L）阻断瞬时外向电流（I-to），可使圆颅恢复。规范ST段，防止VT/VF。结论：右室心外膜动作电位圆顶的下降或丧失会产生跨壁电压梯度，这可能是Brugada综合征和其他具有类似心电图表现的综合征中st段抬高的原因。我们的研究结果还表明，由于第2期再入引起的收缩外活动可以在犬右心室完整壁中出现，并作为VT/VF的触发因素。我们的数据表明I-to阻断（4-氨基吡啶，奎尼丁）是一种有效的药物治疗方法。
Background-The Brugada syndrome is characterized by marked ST-segment elevation in the right precordial ECG leads and is associated with a high incidence of sudden and unexpected arrhythmic death. Our study examines the cellular basis for this syndrome.Methods and Results-Using arterially perfused wedges of canine right ventricle (RV), we simultaneously recorded transmembrane action potentials from 2 epicardial and 1 endocardial sites, together with unipolar electrograms and a transmural EGG. Loss of the action potential dome in epicardium but not endocardium after exposure to pinacidil (2 to 5 mu mol/L), a K+ channel opener, or the combination of a Na+ channel blocker (flecainide, 7 mu mol/L) and acetylcholine (ACh, 2 to 3 mu mol/L) resulted in an abbreviation of epicardial response and a transmural dispersion of repolarization, which caused an ST-segment elevation in the ECG. ACh facilitated loss of the action potential dome, whereas isoproterenol (0.1 to 1 mu mol/L) restored the epicardial dome, thus reducing or eliminating the ST-segment elevation. Heterogeneous loss of the dome caused a marked dispersion of repolarization within the epicardium and transmurally, thus giving rise to phase 2 reentrant extrasystole. which precipitated ventricular tachycardia (VT) and ventricular fibrillation (VF), Transient outward current (I-to) block With 4-aminopyridine (1 to 2 mmol/L) or quinidine (5 mu mol/L) restored the dome. normalized the ST segment, and prevented VT/VF.Conclusions-Depression or loss of the action potential dome in RV epicardium creates a transmural voltage gradient that may be responsible for the ST-segment elevation observed in the Brugada syndrome and other syndromes exhibiting similar ECG manifestations. Our results also demonstrate that extrasystolic activity due to phase 2 reentry can arise in the intact wall of the canine RV and serve as the trigger for VT/VF. Our data point to I-to block (4-aminopyridine, quinidine) as an effective pharmacological treatment.