This paper reviewed the advances on effective constituents and biological activities of coumarins in recent ten years. Coumarins are a group of important natural compounds, and have been found to have multi-biological activities such as anti-HIV, anti-tumor, anti-hypertension, anti-arrhythmia, anti-osteoporosis, assuaging pain, preventing asthma and antisepsis. Therefore, further investigation should emphasize on improving techniques for extraction and separation, searching the effective precursory compound, and synthesizing and screening out courmarin derivatives with high activity and low toxicity.
Animals ; Anti-Arrhythmia Agents ; pharmacology ; Anti-HIV Agents ; pharmacology ; Antihypertensive Agents ; pharmacology ; Antineoplastic Agents, Phytogenic ; pharmacology ; Coumarins ; isolation & purification ; pharmacology ; Humans ; Plants, Medicinal ; chemistry

Anti-Arrhythmia Agents/blood ; Anti-Arrhythmia Agents/*pharmacology ; Blood Pressure/drug effects ; Cell Membrane/drug effects ; Disopyramide/blood ; Membrane Potentials/drug effects

OBJECTIVETo explore the electrophysiological effects of antiarrhythmic drugs on pacemaker cells of left ventricular outflow tract.

METHODSBy using conventional intracellular microelectrode technique to record action potentials, series antiarrhythmic drugs were used to investigate the electrophysiological features and regularities of spontaneous activity of left ventricular outflow tract.

RESULTS(1) Perfusion with 1 micromol/L quinidine resulted in a significant decrease in rate of pacemaker firing (RPF, P < 0.05), velocity of diastolic depolarization (VDD, P < 0.05), amplitude of action potential (APA, P < 0.05), and maximal rate of depolarization (V(max), P < 0.05), and a marked prolonging in 50% and 90% of duration of action potential (APD50 and APD90, P < 0.05). (2) 1 micromol/L lidocaine decreased RPF, VDD, MDP, APA and V(max) significantly (P < 0.05), shortened APD50 and APD90 notably (P < 0.05). (3) 1 micromol/L propafenone led to a significant decrease in RPF (P < 0.01), VDD (P < 0.05), APA (P < 0.05), V(max) (P < 0.01), and a marked prolonging in APD50 (P < 0.01) and APD90 (P < 0.05). (4) Application of 5 micromol/L propranolol resulted in a significant decrease in RPF and VDD (P < 0.01), MDP and APA (P < 0.01), V(max) (P < 0.05) and a notable prolonging in APD50 and APD90 (P < 0.05). (5) Perfusion with 1 micromol/L amiodarone resulted in a significant decrease in RPF and VDD (P < 0.01), APA (P < 0.01), V(max) (P < 0.05), a marked prolonging in APD50 (P < 0.01) and APD90 (P < 0.05). (6) 1 micromol/L verapamil significantly decreased RPF and VDD (P < 0.01), MDP and APA (P < 0.05), V(max) (P < 0.05), notably prolonged APD50 and APD90 (P < 0.01). (7) 50 micromol/L adenosine significantly decreased RPF and VDD (P < 0.05), APA (P < 0.05), V(max) (P < 0.01), markedly shortened APD50 and APD90 (P < 0.05).

CONCLUSIONAll kinds of antiarrhythmic drugs can decrease the autorhythmicity of guinea pig left ventricular outflow tract. By altering APD50 and APD90, they can affect effective refractory period (ERP) and having a significant effect on autorhythmicity of left ventricular outflow tract.

Animals ; Anti-Arrhythmia Agents ; pharmacology ; Electrocardiography ; Guinea Pigs ; Heart Ventricles ; drug effects

OBJECTIVETo investigate the effect and potential mechanism of lysophosphatidic acid (LPA) and antiarrhythmic peptide (AAP10) on rabbit ventricular arrhythmia.

METHODSTwenty-four rabbits were randomly divided into three groups (n = 8 each): control group, LPA group and AAP10 + LPA group. Using arterially perfused rabbit ventricular wedge preparations, transmural ECG and action potentials from both endocardium and epicardium were simultaneously recorded in the whole process of all experiments with two separate floating microeletrodes. The incidence of ventricular arrhythmia post S1S2 stimulation was recorded. Protein levels of nonphosphorylated Cx43 and total Cx43 were evaluated by Western blot. The distribution of nonphosphorylated Cx43 was observed by confocal immunofluorescence microscopy.

RESULTSCompared with the control group, the QT interval, endocardial action potential duration, transmural repolarization dispersion (TDR) and incidence of ventricular arrhythmia were significantly increased and nonphosphorylated Cx43 expression was significantly upregulated in the LPA group. Compared with the LPA group, cotreatment with AAP10 can reduce the QT interval, endocardial action potential duration, TDR and incidence of ventricular arrhythmia (25.0% vs 62.5%, P < 0.01) and downregulate nonphosphorylated Cx43.

CONCLUSIONSLPA could promote the arrhythmia possibly by upregulating nonphosphorylated Cx43 and subsequent gap junction transmission inhibition. Gap junction enhancer AAP10 could attenuate the pro-arrhythmic effect of LPA probably by downregulating myocardial nonphosphorylated Cx43 expression.

Animals ; Anti-Arrhythmia Agents ; pharmacology ; Arrhythmias, Cardiac ; chemically induced ; metabolism ; physiopathology ; Connexin 43 ; metabolism ; Lysophospholipids ; adverse effects ; Oligopeptides ; pharmacology ; Rabbits

BACKGROUNDNifekalant may prevent atrial fibrillation (AF) and possibly be useful in treatment of atrial tachyarrhythmia in patients with severe heart failure. This study investigated the electophysiologic effect of nifekalant on the acute atrial remodeling in rapid atrial pacing (RAP) model of canine.

METHODSTwelve mongrel dogs subjected to rapid stimulation (400 beats/min) at left atrial appendage (LAA) for 24 hours, were randomized into the control group (rapid pacing only, n = 6) and the nifekalant group (intravenous nifekalant therapy immediately after RAP, n = 6). Atrial electrophysiological parameters were measured in right atrium, coronary sinus, LAA, posterior wall of left atrium (PWLA) and left superior pulmonary vein (LSPV), before and after the RAP.

RESULTSIn the control group, the effective refractory periods (ERP) were shortened greatly at all sites, paced dogs had substantially shorter ERPs in the high right atrium, LAA, and LSPV, but fewer changes in the PWLA, the coefficient variation of ERP (COV ERP) was increased significantly. After rapid atrial stimulation, the inducibility of AF increased significantly [induction number: pre-RAP vs post-RAP, 1.00 +/- 0.89 vs 8.17 +/- 2.79, P < 0.01; duration of AF: pre-RAP vs post-RAP, (450.34 +/- 362.59) ms vs (9975.77 +/- 4376.99) ms, P < 0.01]. In the nifekalant group, although the ERPs were prolonged at all sites compared with those in pre-RAP state, only the value at LSPV differed significantly from that in pre-RAP state [pre-RAP vs post-RAP, (102.50 +/- 5.24) ms vs (132.51 +/- 5.20) ms, P < 0.01]; the COV ERP did not change statistically in this group. The inducibility of AF slightly increased but insignificantly after pacing [induction number: pre-RAP vs post-RAP, 0.83 +/- 0.75 vs 1.67 +/- 0.82, P = 0.19; duration of AF: pre-RAP vs post-RAP, (378.67 +/- 317.88) ms vs (1124.08 +/- 1109.77) ms, P = 0.06]. Conduction time values did not alter significantly in either of the two groups after RAP.

CONCLUSIONSIn canine RAP model, nifekalant inhibited ERP shortening and ERP heterogeneity increasing, decreased AF induction. Nifekalant can reverse acute electrical remodeling effect in this model.

Animals ; Anti-Arrhythmia Agents ; pharmacology ; Cardiac Pacing, Artificial ; Dogs ; Female ; Male ; Pyrimidinones ; pharmacology ; Refractory Period, Electrophysiological ; drug effects

This study is to quantify time-varying dominant frequencies in electrocardiogram (ECG) during the ventricular fibrillation (VF). Orthogonal ECG (sagittal, x; transverse, y; and longitudinal, z) and the transvenous two-leads defibrillation systems were set in 19 dogs. Time-frequency analysis was used to assess changes in the dominant frequency within ECG recorded in dogs during trials of 10-30 s of VF. In 4 additional dogs, the dominant frequencies were compared during 10 s of VF before and after administration of amiodarone. Results showed that in the 427 trials of 10 s VF and 335 trials of 30 s VF, average variation in the dominant frequency was considerable, between +/- 12%-18%. The frequencies orthogonal ECG during 10 s VF were distributed symmetrically above and below the mean frequency like a normal distribution. In the 79 trials with administration of amiodarone during 10 s VF in all three ECG, the mean frequencies decreased from 6.5 (x), 7.4 (y) and 7.0 Hz (z) to 6.1, 6.4 and 6.3 Hz (P < 0.01), respectively, and the variation in dominant frequencies decreased from 1.18, 1.38 and 1.19 to 0.98, 1.11 and 1.02 Hz (P < 0.05) respectively. The results confirmed that the frequencies of 10-30 s VF in ECG vary considerably and continuously, and amiodarone decreases this variation.
Amiodarone ; pharmacology ; Animals ; Anti-Arrhythmia Agents ; pharmacology ; Dogs ; Electric Countershock ; Electrocardiography ; drug effects ; Female ; Male ; Ventricular Fibrillation ; physiopathology

OBJECTIVETo explore the antiarrhythmic mechanism of ampelopsin through electrophysiological study in rats.

METHODSThe in vivo experimental groups were as follows:control group, low-dose, middle-dose and high-dose group. Arrhythmia in rats was induced by aconitine injection, and then the antiarrhythmic effects of ampelopsin were studied. Cardiomyocytes were isolated from rats therafter. The whole-cell patch-clamp technique was used to record action potential duration (APD), sodium currents (INa), calcium current (ICa), transient outward potassium currents (Ito) and inward rectifier potassium currents (IK1) in cardiomyocytes.

RESULTSIn vivo experiments showed that the incidence of aconitine-induced experimental arrhythmias in low, middle and high-dose ampelopsin group was significantly lower than that in control group (n = 5 each group, all P < 0.05). In vitro whole-cell patch clamp experiments showed that action potential duration in low, middle and high-dose groups was significantly shorter than that in control group, and amplitude of action potential was also significantly lower in low, middle and high-dose ampelopsin groups than in control group (134.1 ± 6.9), (120.1 ± 7.4), (113.2 ± 9.0), and (101.8 ± 5.1) mV for control, low, middle and high-dose group (n = 9 each group, all P < 0.05).Further research revealed that sodium currents in cardiomyocytes were decreased by low, middle and high-dose ampelopsin from (-36.75 ± 3.60) to (-31.03 ± 2.61), (-26.63 ± 3.72), and (-17.55 ± 4.43) pA/pF (n = 9 each group, all P < 0.05), but the activation voltage for peak potential was not affected by ampelopsin. Moreover, the inward rectifier potassium current was also higher in high-dose ampelopsin group than in control group (P < 0.05). Calcium current and transient outward potassium current were similar among four groups.

CONCLUSIONAmpelopsin exerts anti-arrhythmic effects in this rat model, and the underlying electrophysiological mechanism is partly associated with the inhibition of INa and enhancement of IK1, and prolongation of APD.

Action Potentials ; Animals ; Anti-Arrhythmia Agents ; pharmacology ; Arrhythmias, Cardiac ; Flavonoids ; pharmacology ; Myocytes, Cardiac ; Patch-Clamp Techniques ; Potassium Channels ; Rats

OBJECTIVETo observe the electrophysiological effects of ibutilide on canine and to explore the potential mechanisms of ibutilide on terminating atrial flutter.

METHODSEighteen mongrel dogs were anesthetized and intubated. The heart was exposed through thoracotomy for electrodes implantation. The electrophysiologic variables (heart rate, the conduction of intraatrium and interatrium, the conduction ratio of isthmus, the effective refractory period) were measured in the absence or presence of ibutilide (10 minute infusion with 0.10 mg/kg ibutilide, 30 minutes later with a maintaining dose of 0.01 mg/min).

RESULTSIbutilide significant suppressed sinus atrial node function, the peak effect was observed at 20 - 30 min post drug infusion and heart rate returned to normal at 2 hours post infusion. Post ibutilide infusion, 1 canine developed sinus pause for 5 seconds and 2:1 atrioventricular conduction block was evidenced in another canine. The atrial, ventricular and pulmonary vein effective refractory periods were all significant prolonged (all P < 0.05) post ibutilide infusion. However, conduction of intraatrium, interatrium and isthmus remained unchanged post ibutilide infusion (all P > 0.05).

CONCLUSIONSIbutilide could suppress sinus atrial node and the atrioventricular node function. The mechanism of ibutilide on rapidly terminating atrial flutter might be related to the prolongation of the refractory periods which might then result in the reduction of the whole excitable gap of the reentrant circuit and induce proceed inability of reentrant wavefront.

Animals ; Anti-Arrhythmia Agents ; pharmacology ; Atrial Flutter ; drug therapy ; physiopathology ; Dogs ; Heart Rate ; drug effects ; Male ; Sulfonamides ; pharmacology

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

Berbamine (molecular formular C37H40N2O6) is a bi-benzle-isoquinolyl alkaloid extracted from Berberis poiretil Schneid (genus of Berberis, family of Beridaceae), a kind of Chinese plants. In aspect of cardiovascular pharmacology, berbamine shows actions of anti-arrhythmia, anti-myocardial ischemia, vasodilatating to lower blood pressure, and antithrombosis, it could lower heart function and heart rate. Study on its anti-arrhythmia was the deepest one. The significant anti-arrhythmia action can be achieved by inhibiting ionic channels of sodium, potassium, calcium, etc., negative frequency and negative transduction, improving the diastolic excitation threshold of myocardium, prolonging effective refractory period of myocardium. As a direction of researches on new type of antiarrhythmic herbs and herbal drugs, the study on berbamine is worthy of further research and development.
Alkaloids ; pharmacology ; Anti-Arrhythmia Agents ; pharmacology ; Antihypertensive Agents ; pharmacology ; Benzylisoquinolines ; pharmacology ; Heart Rate ; drug effects ; Ion Channel Gating ; drug effects ; Platelet Aggregation ; Platelet Aggregation Inhibitors ; pharmacology