Atrial-selective inhibition of sodium-channel current by Wenxin Keli is effective in suppressing atrial fibrillation

Abstract

BACKGROUND Wenxin Keli is a Chinese herb extract reported to be of benefit in the treatment of cardiac arrhythmias, cardiac inflammation and heart failure. METHODS AND RESULTS We evaluated the electrophysiologic effects of Wenxin Keli in isolated canine arterially-perfused right atrial preparations with a rim of right ventricular tissue (n=11). Transmembrane action potentials and a pseudo-electrocardiogram were simultaneously recorded. Acetylcholine (ACh, 1 μM) was used to induce atrial fibrillation (AF) and to test the anti-AF potential of Wenxin Keli (5 g/L). Wenxin Keli produced preferential abbreviation of action potential duration (APD90) in atria, but caused atrial-selective prolongation of effective refractory period, due to development of post-repolarization refractoriness. The maximum rate of rise of the action potential upstroke (Vmax) was preferentially reduced in atria. Diastolic threshold of excitation increased in both atria and ventricles, but much more in atria. The duration of the “P wave” (index of atrial conduction time) was prolonged to a much greater extent than the duration of the “QRS complex” (index of ventricular conduction time). Wenxin Keli significantly reduced INa and shifted steady-state inactivation to more negative potentials in HEK293 cells stably expressing SCN5A. Wenxin Keli prevented induction of persistent AF in 100% atria (6/6) and, in another experimental series was found to terminate persistent ACh-mediated AF in 100% of atria (3/3). CONCLUSION Wenxin Keli produces atrial-selective depression of INa-dependent parameters in canine isolated coronary perfused preparations via a unique mechanism and is effective in suppressing AF and preventing its induction, with minimal effects on ventricular electrophysiology.

Brugada Syndrome: Clinical, Genetic, Molecular, Cellular, and Ionic Aspects

“…Wenxin Keli, a traditional Chinese medicine (TCM), in addition to its actions to suppress atrial fibrillation by atrial-selective inhibition of I Na -dependent parameters 254 , has been shown to inhibit I to and thus to suppress VT/VF in experimental models of BrS when combined with low concentrations of quinidine (5 μM). 216 A recent study has also reported the effect of Wenxin Keli to suppress ischemia-induced ventricular arrhythmias.…”

Atria are More Sensitive Than Ventricles to GS-458967-Induced Inhibition of Late Sodium Current

“…Atrial selectivity of peak I Na block has been described for sodium channel blockers that dissociate rapidly from the sodium channel including ranolazine, amiodarone, dronedarone, vernakalant, AZD1305, AVE0118, and Wenxin Keli. 7,[9][10][11][12][17][18][19][20][21] The factors underlying the atrial-selective effects of I Na blockers include a more negative steady state inactivation relationship, a less negative resting membrane potential, and a more gradual phase 3 of the AP in atrial versus ventricular cells as well as a relatively rapid dissociation of the drug from the sodium channel. 7,8,22 GS-458967 dissociates from sodium channels (HEK 293 and atrial myocytes) rapidly with a time constant of 300 to 500 ms (holding potential of À120 mV at 23 C), a value approaching that of lidocaine (L. Belardinelli et al, PhD unpublished observation, 2014).…”

Evaluation of Melissa officinalis (Lemon Balm) effects on heart electrical system

“…Recent studies have also shown the electrophysiological effects of some herbal medicine, which led to expansion of our approach in the use of herbal medicines in the field of cardiac electrophysiology. Some examples include: (Ι) suppressing and preventing effect of Wenxin Keli, a herbal extract, on atrial and ventricular arrhythmias by depression of Ito and INa-dependent electrophysiological parameters (37,38), (ΙΙ) anti-arrhythmic effect of saffron extract (39) and its effects on the Wenckebach block cycle length and nodal functional refractory period in in vitro model (40), (ΙΙΙ) anti-arrhythmic and electrophysiological effects of European Lamiaceae Leonurus cardiaca extract as calcium channels I (Ca.L) blockade, reduction of repolarizing current I (K.r) and prolongation of action potential duration (41) and (IV) bidirectional tachycardia induced by aconites present in a Chinese herbal decoction (42).…”