Electrophysiological basis and genetics of Brugada syndrome
Electrophysiological basis and genetics of Brugada syndrome
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DOI：
10.1111/j.1540-8167.2005.50104.x
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发表时间：
2005-09-01
影响因子：
2.7
通讯作者：
Grant, AO
中科院分区：
文献类型：
--
作者：
Grant, AO
Brugada综合征的基础Brugada综合征是一种原发性心脏病综合征，发生于结构正常的心脏。任何提出的机制都应该解释该综合征的主要特征：ST段和T波改变定位于右胸导联，多个水平的传导减慢相关，钠通道阻滞药物引起的主要ECG改变沉淀或加重，以及室颤的发生。跨心室壁复极的异质性起主要作用。任何使I相期间的净电流梯度向外移动的因素都会夸大复极的正常异质性，并导致该综合征的ST段和T波改变。当外向电流偏移明显时，心外膜区可能发生过早复极，由此产生的梯度可能促使折返。该综合征是一种常染色体显性遗传。然而，75%的临床受影响的个体是男性。在20%的病例中，该综合征与心脏钠通道基因SCN5A的突变有关。突变导致功能丧失，这是由于非功能性蛋白质的合成、蛋白质运输改变或门控改变。降低钠电流的药物可能导致特征性ECG变化，例如钠通道阻滞剂和高钾血症引起的膜去极化。交感神经刺激可逆转心电图改变，减少心律失常复发。通过其非特异性钾通道阻断作用，奎尼丁也可以减少心律失常复发。我们仍然不知道大多数Brugada综合征患者的缺陷的基础。
Basis of Brugada Syndrome. Brugada syndrome is a primary arrhythmic syndrome arising in the structurally normal heart. Any proposed mechanism should account for the major features of the syndrome: localization of the ST segment and T-wave changes to the right precordial leads, association of conduction slowing at several levels, precipitation or aggravation of the major ECG changes by sodium channel-blocking drugs and the occurrence of ventricular fibrillation. Heterogeneity of repolarization across the ventricle wall plays a major role. Any agency that shifts the net current gradient during phase I outward would exaggerate the normal heterogeneity of repolarization and result in the ST segment and T-wave changes characteristic of the syndrome. When the outward current shift is marked, premature repolarization may occur in epicardial zone and the resulting gradient may precipitate reentry. The syndrome is inherited as an autosomal dominant. However, 75% of clinically affected individuals are males. In 20% of cases, the syndrome is associated with mutations of the cardiac sodium channel gene SCN5A. The mutations result in a loss-of-function as a result of the synthesis of a non-functional protein, altered protein trafficking, or change in gating. Agencies that reduce the sodium current may precipitate the characteristic ECG changes, for example, sodium channel blockers and membrane depolarization by hyperkalemia. Sympathetic stimulation may reverse the ECG changes and reduce arrhythmia recurrence. By its nonspecific potassium channel blocking action, quinidine may also reduce arrhythmia recurrence. We still do not know the basis for defect in the majority of patients with Brugada syndrome.