Unmasking of brugada syndrome by lithium.
BACKGROUND
The characteristic ECG pattern of ST-segment elevation in V1 and V2 in the Brugada syndrome is dynamic; it is often intermittently present in affected individuals and can be unmasked by sodium channel blockers, including antiarrhythmic drugs and tricyclic antidepressants. We report here 2 patients who developed the Brugada ECG pattern after administration of lithium, a commonly used drug not previously reported to block cardiac sodium channels.


RESULTS
Lithium induced transient ST-segment elevation (type 1 Brugada pattern) in right precordial leads at therapeutic concentrations in 2 patients with bipolar disorder. Lithium withdrawal in the patients resulted in reversion to type 2 or 3 Brugada patterns or resolution of ST-T abnormalities. In Chinese hamster ovary cells transfected with SCN5A, which encodes the cardiac sodium channel, lithium chloride caused concentration-dependent block of peak INa at levels well below the therapeutic range (IC50 of 6.8+/-0.4 micromol/L).


CONCLUSIONS
The widely used drug lithium is a potent blocker of cardiac sodium channels and may unmask patients with the Brugada syndrome.
Darbar
Dawood
D
Division of Clinical Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232-6602, USA. dawood.darbar@vanderbilt.edu
Yang
Tao
T
Churchwell
Keith
K
Wilde
Arthur A M
AA
Roden
Dan M
DM
D000328:Adult; D000368:Aged; D000818:Animals; D018692:Antimanic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D001714:Bipolar Disorder / Q000188:drug therapy; D002037:Bundle-Branch Block / Q000139:chemically induced*; D006224:Cricetinae; D003412:Cricetulus; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D005260:Female; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects; D018021:Lithium Chloride / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D062554:NAV1.5 Voltage-Gated Sodium Channel; D010053:Ovary / Q000166:cytology / Q000378:metabolism; D018408:Patch-Clamp Techniques; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D014162:Transfection
D018692:Antimanic Agents; D009124:Muscle Proteins; D062554:NAV1.5 Voltage-Gated Sodium Channel; C568320:SCN5A protein, human; D015222:Sodium Channels; D018021:Lithium Chloride