ArticleCirculation research2008
Lidocaine-induced Brugada syndrome phenotype linked to a novel double mutation in the cardiac sodium channel.
Article in Circulation research, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 54 citations in OpenAlex.
- Phase 2 Re-Entry Without IJACC. Clinical electrophysiology · 2023Trial
- Brugada Syndrome: Different Experimental Models and the Role of Human Cardiomyocytes From Induced Pluripotent Stem Cells.Journal of the American Heart Association · 2022Review
- Targeting strategies for oxaliplatin-induced peripheral neuropathy: clinical syndrome, molecular basis, and drug development.Journal of experimental & clinical cancer research : CR · 2021Review
- Distinct Features of Probands With Early Repolarization and Brugada Syndromes Carrying SCN5A Pathogenic Variants.Journal of the American College of Cardiology · 2021Article
- Susceptibility to Ventricular Arrhythmias Resulting from Mutations inStem cells international · 2020Article
- "Pill-in-the-Pocket" Treatment of Propafenone Unmasks ECG Brugada Pattern in an Atrial Fibrillation Patient With a Common SCN5A R1193Q Polymorphism.Frontiers in physiology · 2019Article
- Hyperthermia Influences the Effects of Sodium Channel Blocking Drugs in Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes.PloS one · 2016Article
- A rare loss-of-function SCN5A variant is associated with lidocaine-induced ventricular fibrillation.The pharmacogenomics journal · 2014Article
- Atrial-selective prolongation of refractory period with AVE0118 is due principally to inhibition of sodium channel activity.Journal of cardiovascular pharmacology · 2012Article
- A case for pharmacogenomics in management of cardiac arrhythmias.Indian pacing and electrophysiology journal · 2012Article
- Brugada-like syndrome in infancy presenting with rapid ventricular tachycardia and intraventricular conduction delay.Circulation · 2012Article
- LQT5 masquerading as LQT2: a dominant negative effect of KCNE1-D85N rare polymorphism on KCNH2 current.Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2011Article
- Biophysical and molecular characterization of a novel de novo KCNJ2 mutation associated with Andersen-Tawil syndrome and catecholaminergic polymorphic ventricular tachycardia mimicry.Circulation. Cardiovascular genetics · 2011Article
- Drugs and Brugada syndrome patients: review of the literature, recommendations, and an up-to-date website (www.brugadadrugs.org).Heart rhythm · 2009Review
- Increased sensitivity to local anesthetic drugs: bedside to bench.Circulation research · 2008Article
- Peripheral nerve block with ropivacaine in Brugada syndrome patient: Anesthetic consideration.Saudi journal of anaesthesiaArticle
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11 authors at 6 institutions in 2 countries.
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Abstract
Brugada syndrome has been linked to mutations in SCN5A. Agents that dissociate slowly from the sodium channel such as flecainide and ajmaline unmask the Brugada syndrome electrocardiogram and precipitate ventricular tachycardia/fibrillation. Lidocaine, an agent with rapid dissociation kinetics, has previously been shown to exert no effect in patients with Brugada syndrome. We characterized a novel double mutation of SCN5A (V232I in DI-S4+L1308F in DIII-S4) identified in a rare case of lidocaine (1 mg/kg)-induced Brugada syndrome. We studied lidocaine blockade of I(Na) generated by wild-type and V232I+L1308F mutant cardiac sodium channels expressed in mammalian TSA201 cells using patch clamp techniques. Despite no significant difference in steady-state gating parameters between V232I+L1308F and wild-type sodium currents at baseline, use-dependent inhibition of I(Na) by lidocaine was more pronounced in V232I+L1308F versus wild-type (73.0+/-0.1% versus 18.23+/-0.04% at 10 micromol/L measured at 10 Hz, respectively). A dose of 10 micromol/L lidocaine also caused a more negative shift of steady-state inactivation in V232I+L1308F versus wild-type (-14.1+/-0.3 mV and -4.8+/-0.3 mV, respectively). The individual mutations produced a much less accentuated effect. We report the first case of lidocaine-induced Brugada electrocardiogram phenotype. The double mutation in SCN5A, V232I, and L1308F alters the affinity of the cardiac sodium channel for lidocaine such that the drug assumes Class IC characteristics with potent use-dependent block of the sodium channel. Our results demonstrate an additive effect of the 2 missense mutations to sensitize the sodium channel to lidocaine. These findings suggest caution when treating patients carrying such genetic variations with Class I antiarrhythmic drugs.
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