Vernooy Kevin, Sicouri Serge, Dumaine Robert, Hong Kui, Oliva Antonio, Burashnikov Elena, Timmermans Carl, Delhaas Tammo, Crijns Harry J G M, Antzelevitch Charles, Rodriguez Luz-Maria, Brugada Ramon
Department of Cardiology, Academic Hospital Maastricht, Maastricht, the Netherlands.
Heart Rhythm. 2006 Sep;3(9):1074-8. doi: 10.1016/j.hrthm.2006.05.030. Epub 2006 Jul 7.
Brugada syndrome is an inherited disease associated with sudden cardiac death. The electrocardiographic pattern associated with Brugada syndrome has been linked to the use of sodium channel blockers, including antiarrhythmics, trycyclics and anesthetics.
We report a case of bupivacaine-induced Brugada syndrome, in which we investigated the genetic, biophysical and path physiological mechanism involved.
The patient developed a Brugada-like electrocardiographic pattern twice under the influence of bupivacaine. The first occurrence was accompanied by ventricular tachycardia (VT) which subsided after withdrawal of the anesthetic. The VT was also observed during co-administration of diltiazem and isosorbide-5-mononitrate, agents thought to facilitate ST segment elevation in the Brugada syndrome. Genetic analysis revealed a missense mutation in the alpha subunit of the cardiac sodium channel, SCN5A. Biophysical analysis by whole-cell patch-clamping revealed a reduction in sodium current as a result of the mutation. The study of bupivacaine in the wedge model revealed use-dependent changes in conduction, heterogeneous loss of the action potential dome in RV epicardium and phase 2 re-entry when the preparations were pretreated with low concentrations of the calcium channel blocker verapamil.
Our findings indicate that bupivacaine may induce the electrocardiographic and arrhythmic manifestations of the Brugada syndrome in silent carriers of SCN5A mutations. The data have important implications in the management of patients who develop ST segment elevation when under the influence of anesthetics such as bupivacaine.
Brugada综合征是一种与心源性猝死相关的遗传性疾病。与Brugada综合征相关的心电图模式与钠通道阻滞剂的使用有关，包括抗心律失常药、三环类药物和麻醉剂。
我们报告一例布比卡因诱发的Brugada综合征病例，在此病例中我们研究了其中涉及的遗传、生物物理和病理生理机制。
该患者在布比卡因影响下两次出现类似Brugada综合征的心电图模式。第一次发作伴有室性心动过速（VT），停用麻醉剂后室性心动过速消退。在联合使用地尔硫卓和5-单硝酸异山梨酯时也观察到了室性心动过速，这两种药物被认为会促进Brugada综合征患者的ST段抬高。基因分析显示心脏钠通道α亚基SCN5A存在错义突变。全细胞膜片钳生物物理分析显示该突变导致钠电流减少。在楔形模型中对布比卡因的研究表明，当制剂用低浓度钙通道阻滞剂维拉帕米预处理时，传导存在使用依赖性变化，右心室心外膜动作电位圆顶出现异质性丧失以及2期折返。
我们的研究结果表明，布比卡因可能在SCN5A突变的无症状携带者中诱发Brugada综合征的心电图和心律失常表现。这些数据对在布比卡因等麻醉剂影响下出现ST段抬高的患者的管理具有重要意义。
