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(Circulation Research. 2008;103:325.)
© 2008 American Heart Association, Inc.

Editorials

Increased Sensitivity to Local Anesthetic Drugs

Bedside to Bench

Harry A. Fozzard

From the Cardiac Electrophysiology Laboratory, Department of Medicine, The University of Chicago, Ill.

Correspondence to Dr Harry A. Fozzard, PO Box 574, Dana, NC 28724. E-mail hafozzar@uchicago.edu

See related article, pages 396–404

Key Words: Brugada syndrome • local anesthetics • Na channels

An extract of the first 250 words of the full text is provided, because this article has no abstract.

This issue of Circulation Research contains the surprising report of a middle-aged African American with Brugada syndrome associated with 2 widely separated missense mutations in the Na channel gene and with dramatically increased lidocaine sensitivity.¹ Following a seizure in the emergency room, the patient developed an episode of monomorphic ventricular tachycardia terminated by electric shock. After IV lidocaine was started, the patient quickly developed the ECG characteristics of Brugada phenomenon. Although local anesthetics (LAs) with slow off rates typically induce such ECG changes, this has not been reported for lidocaine. After identifying the 2 mutations in the Na channel subunit gene of this individual, Barajas-Martinez et al¹ exposed the mutated channel to lidocaine and found markedly increased sensitivity to block.

The finding of 2 unrelated mutations in the same Na channel gene is unusual. Ackerman et al² reported that 1 of these mutations, L1308F, is a rare polymorphism (seen once in 319) in an African-American population but not in white, Asian, or Hispanic populations. Barajas-Martinez et al¹ indicated that they have seen this polymorphism in 1% of their white population. No previous studies of lidocaine sensitivity have been reported for this polymorphism, but it now seems possible that individuals with the L1308F polymorphism are at risk of local anesthetic toxicity. This question deserves follow-up.

Why should we care much about rare syndromes such as Brugada when they are a mere drop in the bucket of total cardiac arrhythmic death? They are a window into mechanisms of lethal arrhythmia and their . . . [Full Text of this Article]

Related Article:

Lidocaine-Induced Brugada Syndrome Phenotype Linked to a Novel Double Mutation in the Cardiac Sodium Channel

Hector M. Barajas-Martínez, Dan Hu, Jonathan M. Cordeiro, Yuesheng Wu, Richard J. Kovacs, Henry Meltser, Hong Kui, Burashnikov Elena, Ramon Brugada, Charles Antzelevitch, and Robert Dumaine
Circ. Res. 2008 103: 396-404. [Abstract] [Full Text] [PDF]