Dimethyl lithospermate B, an extract of danshen, suppresses arrhythmogenesis associated with the brugada syndrome

• Published in: Circulation (New York, N.Y.) N.Y.), 2006-03, Vol.113 (11), p.1393-1400
• Main Authors: FISH, Jeffrey M, WELCHONS, Daniel R, KIM, Young-Sup, LEE, Suk-Ho, HO, Won-Kyung, ANTZELEVITCH, Charles
• Format: Article
• Language: English
• Subjects: Animals; Arrhythmias, Cardiac - etiology; Arrhythmias, Cardiac - prevention & control; Biological and medical sciences; Biological Transport - drug effects; Blood and lymphatic vessels; Calcium Channel Blockers - toxicity; Cardiology. Vascular system; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Dogs; Drug Evaluation, Preclinical; Drugs, Chinese Herbal - isolation & purification; Drugs, Chinese Herbal - therapeutic use; Electrocardiography - drug effects; Female; In Vitro Techniques; Injuries of the limb. Injuries of the spine; Male; Medical sciences; NAV1.5 Voltage-Gated Sodium Channel; Pinacidil - toxicity; Plant Extracts - isolation & purification; Plant Extracts - therapeutic use; Plant Roots - chemistry; Potassium Channels - agonists; Salvia miltiorrhiza - chemistry; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Sodium - metabolism; Sodium Channel Agonists; Sodium Channel Blockers - toxicity; Sodium Channels - physiology; Stimulation, Chemical; Terfenadine - toxicity; Traumas. Diseases due to physical agents; Verapamil - toxicity
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/CIRCULATIONAHA.105.601690

Dimethyl lithospermate B (dmLSB) is an extract of Danshen, a traditional Chinese herbal remedy, which slows inactivation of INa, leading to increased inward current during the early phases of the action potential (AP). We hypothesized that this action would be antiarrhythmic in the setting of Brugada syndrome. The Brugada syndrome phenotype was created in canine arterially perfused right ventricular wedge preparations with the use of either terfenadine or verapamil to inhibit INa and ICa or pinacidil to activate IK-ATP. AP recordings were simultaneously recorded from epicardial and endocardial sites together with an ECG. Terfenadine, verapamil, and pinacidil each induced all-or-none repolarization at some epicardial sites but not others, leading to ST-segment elevation as well as an increase in both epicardial and transmural dispersions of repolarization (EDR and TDR, respectively) from 12.9+/-9.6 to 107.0+/-54.8 ms and from 22.4+/-8.1 to 82.2+/-37.4 ms, respectively (P