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

Area of Science:

• Cardiovascular Pharmacology
• Electrophysiology
• Traditional Chinese Medicine

Background:

• Dimethyl lithospermate B (dmLSB), derived from Danshen, modulates sodium current (INa) inactivation.
• This modulation increases inward current during early action potential (AP) phases.
• We investigated dmLSB's potential antiarrhythmic effects in Brugada syndrome.

Purpose of the Study:

• To evaluate the antiarrhythmic efficacy of dmLSB in a Brugada syndrome model.
• To determine if dmLSB can prevent or reverse the proarrhythmic substrate associated with Brugada syndrome.

Main Methods:

• Brugada syndrome phenotype induced in canine right ventricular wedge preparations using terfenadine, verapamil, or pinacidil.
• Simultaneous AP recordings from epicardial and endocardial sites, alongside ECG monitoring.
• Assessment of dmLSB's effect on AP repolarization, repolarization dispersion, and arrhythmogenesis.

Main Results:

• Brugada syndrome induction led to all-or-none repolarization, ST-segment elevation, and increased epicardial and transmural repolarization dispersions (EDR and TDR).
• Phase 2 reentry, extrasystoles, and ventricular arrhythmias were observed.
• Addition of dmLSB (10 micromol/L) restored the epicardial AP dome, significantly reduced EDR and TDR, and abolished all induced arrhythmias in all preparations.

Conclusions:

• Dimethyl lithospermate B demonstrates significant efficacy in eliminating the arrhythmogenic substrate of Brugada syndrome.
• dmLSB warrants further investigation as a potential pharmacological adjunct for patients with Brugada syndrome, possibly complementing implanted cardioverter-defibrillator therapy.