Dimethyl lithospermate B, an extract of Danshen, suppresses arrhythmogenesis associated with the Brugada syndrome
Dimethyl lithospermate B, an extract of Danshen, suppresses arrhythmogenesis associated with the Brugada syndrome
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DOI：
10.1161/circulationaha.105.601690
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发表时间：
2006-03-21
期刊：
影响因子：
37.8
通讯作者：
Antzelevitch, C
中科院分区：
文献类型：
--
作者：
Fish, JM;Welchons, DR;Antzelevitch, C
背景-二甲基石榴石B(DmLSB)是一种传统中草药丹参的提取物，可减缓动作电位(AP)早期I-Na失活，导致内向电流增加。我们假设这种作用在Brugada综合征的背景下是抗心律失常的。方法和结果-在犬动脉灌注的右室楔形制剂中，使用特非那定或异搏定抑制I-Na和I-Ca，或使用吡那地尔激活IK-ATP，建立了Brugada综合征的表型。同时记录心外膜和心内膜部位的AP，并进行心电图检查。特非那定、维拉帕米和吡那地尔分别在某些心外膜部位引起复极或无复极，但在其他部位不引起复极，导致ST段抬高，心外膜和跨室壁复极离散度(EDR和TdR)分别从12.9±9.6和22.4±8.1增加到107.0±54.8ms和82.2±37.4ms(P<；0.05；n=9)。在这种情况下，当心外膜心动过速穹隆从维持的部位传播到丢失的部位时，出现2相折返，产生紧密耦合的室性早搏、室性心动过速和纤颤。在冠脉灌流液中加入dmLSB(10 mU·m o l/L)可恢复心外膜AP穹隆，EDR和TDR分别减少到12.4±/-18.1和24.4±-26.7ms(P<；0.05；n=9)，并能消除9例2相折返性早搏、室性心动过速和纤颤。结论：dmLSB能有效地消除导致Brugada综合征的致心律失常底物，作为植入性心律转复/除颤器的药理辅助应用值得进一步研究。
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.