Increased Sensitivity to Local Anesthetic Drugs

Abstract

See related article, pages 396–404 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 α 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 study can lead to preventive or corrective therapy. Although these monogenetic diseases are rare, the conditions can be reproduced in the laboratory, an invaluable tool that is very difficult to achieve with multifactorial diseases such as regional ischemia. Indeed, …