To evaluate the efficiency and safety between Wenxin Granule and antiarrhythmic drugs in the treatment of atrial fibrillation(AF). A total of 8 major electronic databases(CNKI, WanFang, VIP, CBM, Cochrane Library, Web of Science, PubMed, EMbase) were retrieved since the establishment of the database to January 10, 2019. Two reviewers extracted data, and assessed the methodological quality of the included studies. The Meta-analysis was made by RevMan 5.3 software. Finally, 42 studies involving 4 657 patients were included. The results of Meta-analysis showed that compared with antiarrhythmic drug, the combined administration with Wenxin Granule and antiarrhythmic drug had a better clinical efficiency(OR=3.37, 95%CI[2.69,4.22],I~2=0%,P<0.000 01)and efficacy on cardioversion(OR=2.32,95%CI[1.67,3.22],I~2=0%,P<0.000 01), with reduction in P_d(MD=-5.48,95%CI [-7.32,-3.64],I~2=0%,P<0.000 01)and P_(max)(MD=-9.91,95%CI[-12.86,-6.95],I~2=0%,P<0.000 01). The comparison between the combined application with Wenxin Granule and the single application of amiodarone showed a clinical efficiency(OR=2.89,95%CI[1.96,4.26],I~2=44%,P<0.000 01),and efficacy on sinus rhythm maintenance(OR=2.58,95%CI[1.82,3.66],I~2=3%,P<0.000 01). The comparison between the combined application with Wenxin Granule and the single application of amiodarone showed a clinical efficiency(OR=0.88,95%CI[0.53,1.46],I~2=0%,P=0.63). The combined treatment with Wenxin Granule has a better clinical efficiency in AF better than amiodarone, with no evidence for more benefits from the single administration with Wenxin Granules.
Anti-Arrhythmia Agents ; pharmacology ; Atrial Fibrillation ; drug therapy ; Combined Modality Therapy ; Drugs, Chinese Herbal ; pharmacology ; Electric Countershock ; Humans

OBJECTIVES: To investigate the effect of taurine magnesium coordination compound (TMCC) on torsades de pointes (TdP) in isolated guinea pig hearts. METHODS: Healthy male guinea pigs weighting 250~300 g were randomly divided into 4 groups:①TdP model group (=7):Isolated hearts were perfused by normal K-H solution 20 minutes, then perfused by slowly activated delayed rectifier potassium current(IKs) blocker 10mol/L Chromanol 293B under hypokalemic solution(1.8 mmol/L) to establish TdP model;②~④ TdP model + TMCC group (=6):Isolated hearts were perfused by normal K-H solution for 20 minutes, then perfused by IKs blocker 10mol/L Chromanol 293B under hypokalemic solution(1.8 mmol/L) for 60 minutes, at the same time TMCC which concentration was 1, 2, 4 mmol/L was administered respectively by Langendorff retrograde aortic perfusion method. Cardiac surface electrocardiogram of guinea pigs was collected and recorded by Biopac electrophysiological recorder. Incidence of TdP, transmural dispersion of repolarization (TDR), instability of QT interval were acquired from Lead Ⅱ electrocardiograph (ECG) wave forms to describe the effect of TMCC on TdP model. Datas were acquired at the time of 20 min and pre-TdP, in case there was no TdP observed, a value of 60 min was entered for calculation purpose. RESULTS: Incidence of TdP in TdP model group was 6/7. TdP incidence could be decreased significantly by 1, 2, 4 mmol/L TMCC, and was 5/6, 1/6, 0/6 respectively. Compared with the pre-drug, Chromanol 293B under hypokalemic solution in TdP model group increased TDR(corrected) evidently(<0.01). Compared with the pre-drug, 1, 2, 4 mmol/L TMCC in TdP model + TMCC group could decrease the increased TDR(corrected) induced by Chromanol 293B under hypokalemic solution(>0.05). Compared with the TdP model group, 2, 4 mmol/L TMCC could evidently decrease the instability of QT interval induced by Chromanol 293B under hypokalemic solution(<0.05). During the establishment of TdP model, P waves in more than one cardiac cycle continuously were disappeared in ECG. However, P wave could always be seen independent in ECG acquired from TdP model + TMCC group. CONCLUSIONS TMCC can play the role against TdP through decreasing TDR and instability of QT interval, and inhibiting early after depolarization(EAD).
Animals ; Anti-Arrhythmia Agents ; pharmacology ; Electrocardiography ; Guinea Pigs ; In Vitro Techniques ; Long QT Syndrome ; Magnesium ; pharmacology ; Male ; Random Allocation ; Taurine ; pharmacology ; Torsades de Pointes ; drug therapy

OBJECTIVETo study the effect of allitridum on rapidly delayed rectifier potassium current (IKr) in HEK293 cell line.

METHODSHEK293 cells were transiently transfected with HERG channel cDNA plasmid pcDNA3.1 via Lipofectamine. Allitridum was added to the extracellular solution by partial perfusion after giga seal at the final concentration of 30 µmol/L. Whole-cell patch clamp technique was used to record the HERG currents and gating kinetics before and after allitridum exposure at room temperature.

RESULTSThe amplitude and density of IHERG were both suppressed by allitridum in a voltage-dependent manner. In the presence of allitridum, the peak current of IHERG was reduced from 73.5∓4.3 pA/pF to 42.1∓3.6 pA/pF at the test potential of +50 mV (P<0.01). Allitridum also concentration-dependently decreased the density of the IHERG. The IC50 of allitridum was 34.74 µmol/L with a Hill coefficient of 1.01. Allitridum at 30 µmol/L caused a significant positive shift of the steady-state activation curve of IHERG and a markedly negative shift of the steady-state inactivation of IHERG, and significantly shortened the slow time constants of IHERG deactivation.

CONCLUSIONAllitridum can potently block IHERG in HEK293 cells, which might be the electrophysiological basis for its anti-arrhythmic action.

Allyl Compounds ; pharmacology ; Anti-Arrhythmia Agents ; Delayed Rectifier Potassium Channels ; drug effects ; Ether-A-Go-Go Potassium Channels ; HEK293 Cells ; drug effects ; Humans ; Patch-Clamp Techniques ; Potassium Channel Blockers ; pharmacology ; Sulfides ; pharmacology ; Transfection

The present study was designed to determine the effects of Guanfu base A (GFA) on the late sodium current (INa.L), transient sodium current (INa.T), HERG current (IHERG), and Kv1.5 current (IKv1.5). The values of INa.L, INa.T, IHERG and IKv1.5 were recorded using the whole-cell patch clamp technique. Compared with other channels, GFA showed selective blocking activity in late sodium channel. It inhibited INa.L in a concentration-dependent manner with an IC50 of (1.57 ± 0.14) μmol · L(-1), which was significantly lower than its IC50 values of (21.17 ± 4.51) μmol · L(-1) for the INa.T. The inhibitory effect of GFA on INa,L was not affected by 200 μmol · L(-1) H2O2. It inhibited IHERG with an IC50 of (273 ± 34) μmol · L(-1) and has slight blocking effect on IKv1.5, decreasing IKv1.5 by only 20.6% at 200 μmol · L(-1). In summary, GFA inhibited INa.L selectively and remained similar inhibition in presence of reactive oxygen species. These findings may suggest a novel molecular mechanism for the potential clinical application of GFA in the treatment of cardiovascular disorders.
Analysis of Variance ; Animals ; Anti-Arrhythmia Agents ; pharmacology ; Dose-Response Relationship, Drug ; Female ; Guinea Pigs ; HEK293 Cells ; Heart Ventricles ; drug effects ; Heterocyclic Compounds, 4 or More Rings ; pharmacology ; Humans ; Inhibitory Concentration 50 ; Male ; Membrane Potentials ; drug effects ; Myocytes, Cardiac ; metabolism ; Patch-Clamp Techniques ; Sodium Channel Blockers ; pharmacology ; Sodium Channels ; drug effects

This study was aimed to investigate the role of the delta-opioid receptor (DOR)-β-arrestin1-Bcl-2 signal transduction pathway in the pathogenesis of ulcerative colitis (UC) and the intervention effects of oxymatrine on UC. Forty Sprague-Dawley rats were divided into normal group, model group, oxymatrine-treated group and mesalazine-treated group (n=10 each) at random. The rat UC model was established by intra-colonic injection of trinitrobenzene sulfonic acid in the model group and two treatment groups. The rats in oxymatrine-treated group were subjected to intramuscular injection of oxymatrine [63 mg/(kg·day)] for 15 days, and those in mesalazine-treated group given mesalazine solution [0.5 g/(kg·day)] by gastric lavage for the same days. Animals in normal group and model group were administered 3 mL water by gastric lavage for 15 days. On the 16th day, after fasting for 24 h, the rats were sacrificed for the removal of colon tissues. The expression levels of DOR, β-arrestin1 and Bcl-2 were determined in colon tissues by immunohistochemistry and real-time quantitative polymerase chain reaction (RT-PCR), respectively. It was found that the expression levels of DOR, β-arrestin1 and Bcl-2 protein and mRNA were significantly increased in the model group as compared with the other groups (P<0.05). They were conspicuously decreased in both mesalazine-treated and oxymatrine-treated groups in contrast to the model group (P<0.05). No statistically significant difference was noted in these indices between mesalazine- and oxymatrinetreated groups (P>0.05). This study indicated that the DOR-β-arrestin1-Bcl-2 signal transduction pathway may participate in the pathogenesis of UC. Moreover, oxymatrine can attenuate the development of UC by regulating the DOR-β-arrestin1-Bcl-2 signal transduction pathway.
Alkaloids ; pharmacology ; Animals ; Anti-Arrhythmia Agents ; pharmacology ; Arrestins ; metabolism ; Colitis, Ulcerative ; metabolism ; pathology ; prevention & control ; Male ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Quinolizines ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptors, Opioid, delta ; metabolism ; Signal Transduction ; drug effects ; beta-Arrestins

To study the antiarrhythmic effect of the newly developed alpha/beta-blocker TJ0711, a variety of animal models of arrhythmia were induced by CaCl2, ouabain and ischemia/reperfusion. Glass microelectrode technique was used to observe action potentials of right ventricular papillary muscle of guinea pig. The onset time of arrhythmia induced by CaCl2 was significantly prolonged by TJ0711 at 0.75, 1.5 and 3 mg x kg(-1) doses. TJ0711 (1.5 and 3 mg x kg(-1)) can significantly shorten the ventricular tachycardia (VT) and ventricular fibrillation (VF) duration, the incidence of VF and mortality were significantly reduced. On ischemia-reperfusion-induced arrhythmic model, TJ0711 (0.25, 0.5, 1 and 2 mg x kg(-1)) can significantly reduce the ventricular premature contraction (PVC), VT, VF incidence, mortality, arrhythmia score with a dose-dependent manner. At the same time, rats serum lactate dehydrogenase (LDH) and creatine kinase (CK) activities decreased significantly by TJ0711 (1 and 2 mg x kg(-1)). Ouabain could cause arrhythmia in guinea pigs, when TJ0711 (0.375, 0.75, 1.5 and 3 mg x kg(-1)) was given, the doses of ouabain inducing a variety of arrhythmia PVC, VT, VF, cardiac arrest (CA) were significantly increased with a dose-dependent manner. In the TJ0711 0.1-30 micromol x L(-1) concentration range, guinea pig right ventricular papillary muscle action potential RP (rest potential), APA (action potential amplitude) and V(max) (maximum velocity of depolarization) were not significantly affected. APD20, APD50 and APD90 had a shortening trend but no statistical difference with the increase of TJ0711 concentration. TJ0711 has antiarrhythmic effect on the sympathetic nerve excitement and myocardial cell high calcium animal arrhythmia model. Myocardial action potential zero phase conduction velocity and resting membrane potential were not inhibited by TJ0711. APD20, APD50 and APD90 were shortened by TJ0711 at high concentration. Its antiarrhythmic action mechanism may be besides the action of blocking beta1 receptor, may also have a strong selective blocking action on alpha1 receptor and reducing intracellular calcium concentration.
Action Potentials ; drug effects ; Adrenergic alpha-Antagonists ; administration & dosage ; pharmacology ; Adrenergic beta-Antagonists ; administration & dosage ; pharmacology ; Animals ; Anti-Arrhythmia Agents ; administration & dosage ; pharmacology ; Arrhythmias, Cardiac ; blood ; chemically induced ; etiology ; pathology ; physiopathology ; Calcium Chloride ; Creatine Kinase ; blood ; Dose-Response Relationship, Drug ; Female ; Guinea Pigs ; Heart Ventricles ; cytology ; Lactate Dehydrogenases ; blood ; Male ; Myocardial Reperfusion Injury ; complications ; Myocytes, Cardiac ; drug effects ; physiology ; Ouabain ; Papillary Muscles ; cytology ; Phenoxypropanolamines ; administration & dosage ; pharmacology ; Random Allocation ; Rats ; Rats, Sprague-Dawley

The aim of this study was to investigate the effect of polydatin on transient outward potassium channel current (Ito), steady-state outward potassium channel current (Iss) and inward rectifier potassium channel current (IK1) in ventricular myocytes of rat using the whole-cell patch clamp technique. The results showed: (1) Polydatin (above 10 µmol/L) increased IK1 of ventricular myocytes in a non-concentration dependent manner. (2) Polydatin neither had any effect on Ito peak current of ventricular myocytes, nor changed activation, inactivation and recovery kinetics of Ito. (3) Polydatin had no effect on Iss of ventricular myocytes. These results suggest that polydatin enhances IK1 channel activity, but has no effect on Ito and Iss channels in rat ventricular myocytes, which might be one of the ionic mechanisms for antiarrhythmic effect of polydatin.
Animals ; Anti-Arrhythmia Agents ; pharmacology ; Glucosides ; pharmacology ; Myocytes, Cardiac ; drug effects ; Patch-Clamp Techniques ; Potassium Channels, Inwardly Rectifying ; metabolism ; Rats ; Stilbenes ; pharmacology

OBJECTIVEImmunofluorescence and Western blot methods were adopted for qualitative and quantitative detections of the effect of different concentrations of berberine, liensinine and neferine on the expression of stable transfection in HERG potassium channel in HEK-293 cells, as well as the effect of different concentrations of berberine on protein expression of Ikr channel in cardiac muscular tissues, in order to investigate the anti-arrhythmic mechanism of berberine, liensinine and neferine.

METHODWestern blot method was used to detect protein expression of HERG channel in HERG-HEK cells. Immunofluorescence method as well as confocal laser microscope were used to detect the effect of different concentrations of berberine, liensinine and neferine on protein expression of HERG channel. Western blot method was used to detect the effect of different concentrations of berberine on protein expression of Ikr channel in cardiac muscular tissues as well as the effect of berberine, liensinine and neferine on protein expression of stable transfection in HERG potassium channel in HEK-293 cells.

RESULTWestern blot experiment manifested that stable transfection of HEK293 cells containing HERG genes could increase protein expression of HERG channel. Berberine (10, 30 micromol x L(-1)) remarkably inhibited protein expression of HERG channel in HERG-HEK cells (P < 0.01). Berberine (10, 20 mg x kg(-1)) also inhibited protein expression of Ikr channel in rat ventricular tissues (P < 0.05). Liensinine (3, 10, 30 micromol x L(-1)) increased protein expression of HERG channel in HERG-HEK cells (P < 0.05). Neferine showed no effect on protein expression of HERG channel in HERG-HEK cells.

CONCLUSIONThe stably transfection of HERG-HEK cells can increase protein expression of HERG channel. Berberine shows inhibitory effect on protein expressions of in vitro HERG-HEK cells and Ikr channel in rat ventricular tissues. Liensinine improves protein expression of HERG channe in HERG-HEK cells. Neferine shows no effect on protein expression of HERG channel.

Animals ; Anti-Arrhythmia Agents ; analysis ; pharmacology ; Arrhythmias, Cardiac ; drug therapy ; Benzylisoquinolines ; analysis ; pharmacology ; Berberine ; analysis ; pharmacology ; Blotting, Western ; Dose-Response Relationship, Drug ; ERG1 Potassium Channel ; Ether-A-Go-Go Potassium Channels ; drug effects ; metabolism ; Fluorescent Antibody Technique ; Gene Expression Regulation ; drug effects ; HEK293 Cells ; Humans ; Isoquinolines ; analysis ; pharmacology ; Male ; Phenols ; analysis ; pharmacology ; Rats

Abnormal enhanced transmural dispersion of repolarization (TDR) plays an important role in the maintaining of the severe ventricular arrhythmias such as torsades de pointes (TDP) which can be induced in long-QT (LQT) syndrome. Taking advantage of an in vitro rabbit model of LQT2, we detected the effects of KN-93, a CaM-dependent kinase (CaMK) II inhibitor on repolarization heterogeneity of ventricular myocardium. Using the monophasic action potential recording technique, the action potentials of epicardium and endocardium were recorded in rabbit cardiac wedge infused with hypokalemic, hypomagnesaemic Tyrode's solution. At a basic length (BCL) of 2000 ms, LQT2 model was successfully mimicked with the perfusion of 0.5 μmol/L E-4031, QT intervals and the interval from the peak of T wave to the end of T wave (Tp-e) were prolonged, and Tp-e/QT increased. Besides, TDR was increased and the occurrence rate of arrhythmias like EAD, R-on-T extrasystole, and TDP increased under the above condition. Pretreatment with KN-93 (0.5 μmol/L) could inhibit EAD, R-on-T extrasystole, and TDP induced by E-4031 without affecting QT interval, Tp-e, and Tp-e/QT. This study demonstrated KN-93, a CaMKII inhibitor, can inhibit EADs which are the triggers of TDP, resulting in the suppression of TDP induced by LQT2 without affecting TDR.
Action Potentials ; drug effects ; Animals ; Anti-Arrhythmia Agents ; pharmacology ; Arrhythmias, Cardiac ; etiology ; physiopathology ; prevention & control ; Benzylamines ; pharmacology ; Calcium-Calmodulin-Dependent Protein Kinase Type 2 ; antagonists & inhibitors ; metabolism ; Electrocardiography ; Electrophysiologic Techniques, Cardiac ; Endocardium ; drug effects ; physiopathology ; Heart ; drug effects ; physiopathology ; In Vitro Techniques ; Long QT Syndrome ; complications ; Pericardium ; drug effects ; physiopathology ; Piperidines ; pharmacology ; Protein Kinase Inhibitors ; pharmacology ; Pyridines ; pharmacology ; Rabbits ; Sulfonamides ; pharmacology ; Torsades de Pointes ; etiology ; physiopathology ; prevention & control

Due to the complicated pathogenesis of cardiac arrhythmia, the safe and effective therapeutic strategies for cardiac arrhythmia remain an urgent medical problems in the recent years. In this paper, we introduced the research practice of anti-arrhythmic agents targeting on potassium ion channel. The research progress of anti-arrhythmic agents in up-to-date literatures were also reviewed and prospected.
Amiodarone ; analogs & derivatives ; chemistry ; pharmacology ; therapeutic use ; Animals ; Anti-Arrhythmia Agents ; chemistry ; pharmacology ; therapeutic use ; Arrhythmias, Cardiac ; drug therapy ; physiopathology ; Humans ; Hydantoins ; Imidazolidines ; chemistry ; pharmacology ; therapeutic use ; Molecular Structure ; Piperazines ; chemistry ; pharmacology ; therapeutic use ; Potassium Channel Blockers ; pharmacology ; therapeutic use ; Potassium Channels ; drug effects