Dimethyl lithospermate B, an extract of Danshen, suppresses arrhythmogenesis associated with the Brugada syndrome

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 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 < 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 mu mol/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.