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(Circulation. 2006;113:1393-1400.)
© 2006 American Heart Association, Inc.

Arrhythmia/Electrophysiology

Dimethyl Lithospermate B, an Extract of Danshen, Suppresses Arrhythmogenesis Associated With the Brugada Syndrome

Jeffrey M. Fish, DVM; Daniel R. Welchons; Young-Sup Kim, PhD; Suk-Ho Lee, MD, PhD; Won-Kyung Ho, MD, PhD; Charles Antzelevitch, PhD

From the Masonic Medical Research Laboratory, Utica, NY (J.M.F., D.R.W., C.A.); Korea Research Institute of Chemical Technology, Daejeon, Republic of Korea (Y.K.); and National Research Laboratory for Cell Physiology and Department of Physiology, Seoul National University College of Medicine, Seoul, Republic of Korea (S.L., W.H.).

Correspondence to Dr Jeffrey M. Fish, Masonic Medical Research Laboratory, 2150 Bleecker St, Utica, NY 13501-1787. E-mail fish{at}mmrl.edu

Received November 14, 2005; revision received January 9, 2006; accepted January 13, 2006.

Background— Dimethyl lithospermate B (dmLSB) is an extract of Danshen, a traditional Chinese herbal remedy, which slows inactivation of I_Na, 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.

Methods and Results— The Brugada syndrome phenotype was created in canine arterially perfused right ventricular wedge preparations with the use of either terfenadine or verapamil to inhibit I_Na and I_Ca or pinacidil to activate I_K-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<0.05; n=9). Under these conditions, phase 2 reentry developed as the epicardial AP dome propagated from sites where it was maintained to sites at which it was lost, generating closely coupled extrasystoles and ventricular tachycardia and fibrillation. Addition of dmLSB (10 µmol/L) to the coronary perfusate restored the epicardial AP dome, reduced EDR and TDR to 12.4±18.1 and 24.4±26.7 ms, respectively (P<0.05; n=9), and abolished phase 2 reentry-induced extrasystoles and ventricular tachycardia and fibrillation in 9 of 9 preparations.

Conclusions— Our data suggest that dmLSB is effective in eliminating the arrhythmogenic substrate responsible for the Brugada syndrome and that it deserves further study as a pharmacological adjunct to implanted cardioverter/defibrillator usage.

Key Words: action potentials • arrhythmia • antiarrhythmia agents • sudden death • reentry

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