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

Cited 65 time in Web of Science Cited 82 time in Scopus
Authors
Fish, Jeffrey M.; Welchons, Daniel R.; Kim, Young-Sup; Lee, Suk-Ho; Ho, Won-Kyung; Antzelevitch, Charles
Issue Date
2005-03-15
Publisher
American Heart Association
Citation
Circulation. 2006 Mar 21;113(11):1393-400. Epub 2006 Mar 13.
Keywords
AnimalsArrhythmias, Cardiac/etiology/*prevention & controlBiological Transport/drug effectsCalcium Channel Blockers/toxicityDogsDrug Evaluation, PreclinicalDrugs, Chinese Herbal/isolation & purification/*therapeutic useElectrocardiography/drug effectsFemaleMalePinacidil/toxicityPlant Extracts/isolation & purification/*therapeutic usePlant Roots/chemistryPotassium Channels/agonistsSalvia miltiorrhiza/*chemistrySodium/metabolismSodium Channel Blockers/toxicitySodium Channels/*agonists/physiologyStimulation, ChemicalTerfenadine/toxicityVerapamil/toxicity
Abstract
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.
ISSN
1524-4539 (Electronic)
Language
English
URI
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16534004

http://hdl.handle.net/10371/28226
DOI
https://doi.org/10.1161/CIRCULATIONAHA.105.601690
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College of Medicine/School of Medicine (의과대학/대학원)Dept. of Physiology (생리학교실)Journal Papers (저널논문_생리학교실)
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