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 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. 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 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<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 micromol/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

Investigational therapies for non-muscle invasive bladder cancer

Importance of the field: Bacillus Calmette-Guérin (BCG) is currently the most effective adjuvant intravesical agent at preventing disease recurrence and the only therapy shown to inhibit disease progression in non-muscle invasive bladder cancer (NMIBC). However, recurrence rates as high as 30% and significant local/systemic toxicity have resulted in an increased interest in the use of alternative intravesical agents. Areas covered in the review: Our aim is to discuss recent clinical trial evidence utilizing novel intravesical agents for treatment of NMIBC. A systematic literature review was performed via the National Center for Biotechnology Information databases to identify pertinent studies from 2000-2009. What the reader will gain: A durable response has been demonstrated with alternative agents in patients refractory to or intolerant of BCG. This review compares the merits and shortcomings of these emerging agents, focusing on clinical trial safety and efficacy results. Take home message: Despite recent enthusiasm for novel agents, radical cystectomy remains the treatment of choice for patients with NMIBC who have failed intravesical therapy. However, evidence is accumulating that novel agents provide an efficacious alternative in patients refractory or intolerable to BCG or unfit for cystectomy. Further randomized prospective data are required to demonstrate a recurrence-and progression-free benefit compared with BCG. © 2010 Informa UK Ltd