Optimal antiarrhythmic drug therapy for electrical storm

Electrical storm, defined as 3 or more separate episodes of ventricular tachycardia or ventricular fibrillation within 24 hours, carries significant morbidity and mortality. These unstable ventricular arrhythmias have been described with a variety of conditions including ischemic heart disease, structural heart disease, and genetic conditions. While implantable cardioverter defibrillator implantation and ablation may be indicated and required, anti- arrhythmic medication remains an important adjunctive therapy for these persons.

Use of antiarrhythmic drugs in elderly patients

Human aging is a global issue with important implications for current and future incidence and prevalence of health conditions and disability. Cardiac arrhythmias, including atrial fibrillation, sudden cardiac death, and bradycardia requiring pacemaker placement, all increase exponentially after the age of 60. It is important to distinguish between the normal, physiological consequences of aging on cardiac electrophysiology and the abnormal, pathological alterations. The age-related cardiac changes include ventricular hypertrophy, senile amyloidosis, cardiac valvular degenerative changes and annular calcification, fibrous infiltration of the conduction system, and loss of natural pacemaker cells and these changes could have a profound effect on the development of arrhythmias. The age-related cardiac electrophysiological changes include up- and down-regulation of specific ion channel expression and intmcellular Ca2＋ overload which promote the development of cardiac arrhythmias. As ion channels are the substrates of antiarrhythmic drugs, it follows that the pharmacokinetics and pharmacodynamics of these drugs will also change with age. Aging alters the absorption, distribution, metabolism, and elimination of antiarrhythmic drugs, so liver and kidney function must be monitored to avoid potential adverse drug effects, and antiarrhythmic dosing may need to be adjusted for age. Elderly patients are also more susceptible to the side effects of many antiarrhytbanics, including bradycardia, orthostatic hypotension, urinary retention, and falls. Moreover, the choice of antiarrhythmic drugs in the elderly patient is frequently complicated by the presence of co-morbid conditions and by polypharmacy, and the astute physician must pay careful attention to potential drug-drug interactions. Finally, it is important to remember that the use of antiarrhythmic drugs in elderly patients must be individualized and tailored to each patient＇s physiology, disease processes, and medication regimen.

Radioimmunoassay of Antiarrhythmic Peptide and Its application

To establish a specific and sensitive radioimmunoassay (RIA) for antiarrhythmic peptide (AAP) and study serum AAP levels in normal Sprague-Dawley rats (NR) and spontaneous hypertension rats (SHR), AAP-bovine serum albumin (BSA) conjugate was prepared by ammonium bicarbonate method. The New Zealand rabbits were immunized by administering intradermally the conjugate. Then the rabbit anti-AAP serum was produced and iodinated AAP was made by Bolton-Hunter method. The RIA for serum AAP was set up and serum AAP levels in NR and SHR were determined. The minimal detectable range of the AAP RIA was (0.45±0.06) μg/L. The affinity constant for antiserum was 1.05×10 9 L/mol, and the rate of cross-reactivity with atrial peptide (AP) and human growth hormone (hGH) were 0.12 % and 0.20 %, respectively. The mean recovery rate of high, medium and low doses was 97.6 %, and the mean coefficients of variation for intra- and interbath-assay were (6.43±0.85) % and (9.62±1.04) %, respectively. The mean levels of AAP in NR with different age (3 months, 8-10 months and 18-20 months) were (1.75±0.13) μg/L, (1.74±0.11) μg/L and (1.79±0.15) μg/L, respectively, while those in SHR with different age (3 months, 8-10 months and 18-20 months) were (2.38±0.35) μg/L, (2.54±0.25) μg/L and (2.83±0.21) μg/L, respectively. The levels of serum AAP showed a positive correlation with blood pressure (r=0.8667, P<0.05). It was indicated that this AAP RIA had high specificity, high accuracy and good reproducibility. The levels of serum AAP had a close relation with blood pressure.

The trend of change in catheter ablation versus antiarrhythmic drugs for the management of atrial fibrillation over time： a meta-analysis and meta-regression

Objective To evaluate the trend of change in the efficacy and safety of catheter ablation compared with antiarrhythmic drug therapy （ADT） for rhythm control in patients with atrial fibrillation （AF） over time. Methods The online databases PubMed and EMBASE were searched for relevant studies. STATA software （version 12.0） was used to perform the meta-analysis and meta-regression. Results Fifteen randomized controlled trials including 2249 patients with AF were identified. The pooled results showed that catheter ablation was associated with a 52% reduction in the risk of AF recurrence compared with ADT [risk ratio （RR） = 0.48, 95% confidence interval （CI）： 0.40-0.57, I2 = 70.7%）. Subgroup analyses showed that catheter ablation exhibited less efficacy in studies after 2011 compared to studies before 2011 （RR = 0.61, 95% CI： 0.54-0.68, I2 = 9.3% and RR = 0.34, 95% CI： 0.24-0.47, I2 = 69.9%, respectively）, and the safety outcome showed a 1.08-fold higher incidence of adverse events （14.2% vs. 7.3%; RR = 1.08, 95% CI： 1.04-1.13） in studies after 2011. Conclusions Catheter ablation appears to be superior to ADT for rhythm control. However, less efficacy and a higher rate of adverse events were observed in studies after 2011 compared to studies before 2011.

Changes in Phosphorylation of Connexin43 in Rats during Acute Myocardial Hypoxia and Effects of Antiarrhythmic Peptide on the Phosphorylation

In order to confirm the hypothesis that during acute hypoxia, the antiarrhythmic peptide (AAP10) could improve conductance by changing the phosphorylation state of connexin43 (Cx43), isolated perfused rat hearts were randomly divided into three groups: control, hypoxia and AAP10 (n=9 in each group). The change in Cx43 phosphorylation was tested by Western-blot; the distribu- tion of Cx43 was observed by confocal immunofluorescence microscopy. Western-blot analysis re- vealed that the expression of total Cx43 protein was significantly decreased during acute hypoxia, while nonphosphorylated Cx43 (NP-Cx43) was unchanged. AAP10 could increase the expression of total Cx43 protein, but had no effects on the NP-Cx43 protein. Immunofluorescence study showed that during acute hypoxia, both total Cx43 and NP-Cx43 proteins were greatly decreased, while AAP10 only increased the expression of total Cx43 protein, but had no effect of the NP-Cx43 protein expression. These findings suggested that the decrease of intercellular communication may be associ- ated with the reduction of phosphorylated Cx43 (p-Cx43) and translocation of NP-Cx43 from the surface of gap junction into intracellular pools during acute hypoxia. AAP10 can improve intercelluar communication by enhancing phosphorylation of Cx43.

Antiarrhythmic peptide AAP10 prevents ventricular arrhythmia in rabbit LQT2 model

Background and Objective Increased transmural dispersion ofrepolarization (TDR) has been shown to contribute to initiation and maintenance of ventricular arrhythmia in long QT syndromes (LQTS).Intercellular uncoupling through gap junctions is an important mechanism for maintaining TDR in both intact and diseased heart.The present study was to test the hypothesis that improving gap junction communication reduces TDR and prevents ventricular arrhythmia in rabbit LQT2 model.Methods An arterially perfused rabbit left ventricular preparation and E4031 (0.5μmol/L) were used to establish a model of LQT2.Preparations were randomly assigned to control (n=10),AAP-100nmol/L(n=10),AAP-500nM(n=10) groups.Transmural ECG as well as action potentials from both endocardium and epicardium was simultaneously recorded.Results In LQT2 model,presence of 500nmol/L AAP 10 reduced endocardial action potential and TDR and prevented ventricular arrhythmia comparing with the control and AAP 100nmol/ L groups (P【0.05).Conclusions The presence of 500 nmol/L AAP10 reduces TDR and prevents ventricular arrhythmia in rabbit ventricular model of LQT2.This study suggests a possible role of GJs in TDR in rabbit LQT2 model and indicates a new clinical approach to the management of LQTS.

Long-term stroke rates after catheter ablation or antiarrhythmic drug therapy for atrial fibrillation： a meta-analysis of randomized trials

Background Atrial fibrillation （AF） is an independent risk factor for ischemic stroke and is associated with increased risk of death. Randomized studies suggest improved quality of life for patients with AF after successful catheter ablation compared to antiarrhythmic drug therapy. The value of ablation in long-term risk of ischemic stroke, however, has not been assessed. We conducted a meta-analysis to determine whether AF ablation reduces the long-term risk of stroke compared to antiarrhythmic drug therapy in randomized controlled trials. Methods ＆ Results PubMed and the Cochrane Central Register were searched for randomized trials from January 1990 to December 2014 comparing AF catheter ablation to drug therapy. The results are reported as risk differences （RDs） and 95% CI. Thirteen trials were analyzed with 1097 patients treated by catheter ablation and 855 patients received antiarrhythmic drug therapy. Overall, seven patients （0.64%） in the catheter ablation group had ischemic stroke or transient ischemic attacks vs. two patients （0.23%） in the drug therapy group. No difference was shown in the rate of stroke or transient ischemic attack between ablation and drug therapy （RD： 0.003, 95% CI： -0.006 to 0.012, P = 0.470）, and no evidence of heterogeneity was observed （I^2 = 0, P = 0.981）. No potential publication bias was found. There was also no difference in mortality between the two groups （RD： -0.004, 95% CI： -0.014 to 0.006, P = 0.472）. Conclusions This meta-analysis of randomized controlled trials showed similar rates of ischemic stroke or transient ischemic attack and death in AF patients undergoing catheter ablation compared to drug therapy. A larger prospective randomized trial to confirm this finding is warranted.

Gate-related receptor hypothesis for sodium-channel blocker antiarrhythmic agents

Sodium-channel blocker is an important class of drugs(Class Ⅰ) used in antiarrhythmictherapy. Its antiarrhythmic effects are mainly due to its capability of blocking cardiac sodiumchannels. Several hypotheses have been offered to explain the mechanisms of action of so-dium-channel blocker, in which the modulated receptor hypothesis (MRH) and guarded re-

Antiarrhythmic drug usage and prostate cancer： a population-based cohort study

Even though the relationship between antiarrhythmic drug usage and subsequent prostate cancer （PCa） risk has recently been highlighted, relevant findings in the previous literature are still inconsistent. In addition, very few studies have attempted to investigate the association between sodium channel blockers or potassium channel blockers for arrhythmia and the subsequent PCa risk. Therefore, this cohort study aimed to find the relationship between antiarrhythmic drug usage and the subsequent PCa risk using a population-based dataset. The data used in this study were derived from the Longitudinal Health Insurance Database 2005, Taiwan, China. We respectively identified 9988 sodium channel blocker users, 3663 potassium channel blocker users, 65 966 beta-blocker users, 23 366 calcium channel blockers users, and 7031 digoxin users as the study cohorts. The matched comparison cohorts （one comparison subject for each antiarrhythmic drug user） were selected from the same dataset. Each patient was tracked for a 5-year period to define those who were subsequently diagnosed with PCa. After adjusting for sociodemographic characteristics, comorbidities, and age, Cox proportional hazard regressions found that the hazard ratio （HR） of subsequent PCa for sodium channel blocker users was 1.12 （95% confidence interval [CI]： 0.84-1.50）, for potassium channel blocker users was 0.89 （95% CI. 0.59-1.34）, for beta-blocker users was 1.08 （95% Ch 0.96-1.22）, for calcium channel blocker users was 1.14 （95% Ch 0.95-1.36）, and for digoxin users was 0.89 （95% Ch 0.67-1.18）, compared to their matched nonusers. We concluded that there were no statistical associations between different types of antiarrhvthmic drug usage and subsequent PCa risk.

Effects of IQ_23 on the Repolarization and Both Components of the Delayed Rectifier Potassium Current in Guinea Pig Ventricular Myocytcs

Using patch clamp whole cell recording techiques, we examined the effects ofIQ_23, a benzyl-isoquinoline derivative with antiarrhythmic activities, on the action potential (AP) andpotassium currents in single guinea pig ventricular myocytes. The results showed that IQ_23 at 10, 30and 100 μmol ·L_-1 slowed the repolarization in AP dose-dependently. The APD_90 were prolonged by15%, 28% and 31% respectively. This effect did not depend on the extracellular Ca^2+. In voltageclamp mode, IQ_23 effectively blocked both the components of the delayed rectifier potassium current(I_k), i.e., I_ks and I_kr. At concentrations of 30 and 100 μmol· L^-1, IQ_23 suppressed I_ks by 21% and 26%and suppressed I_kr by 67% and 86% respectively. But even at 100 μmol·L^-1, IQ_23 had little effect onthe inward rectifier potassium current (I_k1). It is concluded: 1. IQ_23 can dose-dependently prolongAPD in the ventriculas myocytes of guinea pig, the effect does not depend on the extracellular Ca^2+; 2.IQ_23 blocks both I_ks and Ikr in the ventricular myocytes without obvious specificities between them.

Effects of IQ23 on the Repolarization and Both Components of the Delayed Rectifier Potassium Current in Guinea Pig Ventricular Myocytcs

Using patch clamp whole cell recording techiques, we examined the effects ofIQ23, a benzyl-isoquinoline derivative with antiarrhythmic activities, on the action potential （AP） andpotassium currents in single guinea pig ventricular myocytes. The results showed that IQ23 at 10, 30and 100 μmol ·L-1 slowed the repolarization in AP dose-dependently. The APD90 were prolonged by15%, 28% and 31% respectively. This effect did not depend on the extracellular Ca2+. In voltageclamp mode, IQ23 effectively blocked both the components of the delayed rectifier potassium current（Ik）, i.e., Iks and Ikr. At concentrations of 30 and 100 μmol· L-1, IQ23 suppressed Iks by 21% and 26%and suppressed Ikr by 67% and 86% respectively. But even at 100 μmol·L-1, IQ23 had little effect onthe inward rectifier potassium current （Ik1）. It is concluded: 1. IQ23 can dose-dependently prolongAPD in the ventriculas myocytes of guinea pig, the effect does not depend on the extracellular Ca2+; 2.IQ23 blocks both Iks and Ikr in the ventricular myocytes without obvious specificities between them.

Flecainide: Current status and perspectives in arrhythmia management

Flecainide acetate is a class IC antiarrhythmic agent and its clinical efficacy has been confirmed by the results of several clinical trials. Nowadays, flecainide is recommended as one of the first line therapies for pharmacological conversion as well as maintenance of sinus rhythm in patients with atrial fibrillation and/or supraventricular tachycardias. Based on the Cardiac Arrhythmia Suppression Trial study results, flecainide is not recommended in patients with structural heart disease due to high proarrhythmic risk. Recent data support the role of flecainide in preventing ventricular tachyarrhythmias in patients with catecholaminergic polymorphic ventricular tachycardia associated both with ryanodine receptor and calsequestrin mutations. We herein review the current clinical data related to flecainide use in clinical practice and some concerns about its role in the management of patients with coronary artery disease.

Acupuncture for paroxysmal and persistent atrial fibrillation:An effective non-pharmacological tool?

In Traditional Chinese Medicine,stimulation of the Neiguan spot has been utilized to treat palpitations and symptoms related to different cardiovascular diseases.We evaluated whether acupuncture might exert an antiarrhythmic effect on patients with paroxysmal or persistent atrial fibrillation(AF).Two sets of data are reviewed.The first included patients with persistent AF who underwent electrical cardioversion to restore sinus rhythm.The second included patients with symptomatic paroxysmal AF.All subjects had normal ventricular function.Acupuncture treatment consisted of 10 acupuncture sessions on a once a week basis with puncturing of the Neiguan,Shenmen and Xinshu spots.In patients with persistent AF,the recurrence rate after acupuncture treatment was similar to that observed in patients on amiodarone,but significantly smaller than that measured after sham acupuncture treatment or in the absence of any antiarrhythmic drugs.In a small group of patients with paroxysmal AF,acupuncture resulted in a significant reduction in the number and duration of symptomatic AF episodes.In conclusion,we observed that acupuncture of the Neiguan spot was associated with an antiarrhythmic effect,which was evident in patients with both persistent and paroxysmal AF.These preliminary data,observed in 2 small groups of AF patients,need to be validated in a larger population but strongly suggest that acupuncture may be an effective non-invasive and safe antiarrhythmic tool in the management of these patients.

Present concepts in management of atrial fibrillation:From drug therapy to ablation

Atrial fibrillation(AF) management requires knowledge of its pattern of presentation,underlying conditions,and decisions about restoration and maintenance of sinus rhythm,control of the ventricular rate,and antithrombotic therapy.Maintenance of sinus rhythm is a desirable goal in AF patients because the prevention of recurrence may improve cardiac function,relieve symptoms and reduce the likelihood of adverse events.Anti-arrhythmic drug therapy is the first-line treatment for patients with paroxysmal and persistent AF based on current guidelines.However,currently used drugs have limited efficacy and cause cardiac and extracardiac toxicity.Thus,there is a continued need to develop new drugs,device and ablative approaches to rhythm management.Additionally,simpler and safer stroke prevention regimens are needed for AF patients on life-long anticoagulation,including occlusion of the left atrial appendage.The results of the Randomized Evaluation of Long-Term Anticoagulant Therapy study are encouraging in these settings.Knowledge on the pathophysiology of AF is rapidly expanding and identification of focally localized triggers has led to the development of new treatment options for this arrhythmia.Conversely,the clinical decision whether to restore and maintain sinus rhythm or simply control the ventricular rate has remained a matter of intense debate.In the minority of patients in whom AF cannot be adequately managed by pharmacological therapy,the most appropriate type of non-pharmacological therapy must be selected on an individualized basis.Curative treatment of AF with catheter ablation is now a legitimate option for a large number of patients.The evolution of hybrid therapy,in which two or more different strategies are employed in the same patient,may be an effective approach to management of AF.In any case,planning a treatment regimen for AF should include evaluation of the risks inherent in the use of various drugs as well as more invasive strategies.

EFFECTS OF AMIODARONE AND SOME CLASS ⅠAGENTS ON QT DISPERSION

Objective To investigate the elfects of some class Ⅰ antiarrhythmic agents on QT dispersion and compared with those of amiodarone. Methods Group I was composed of 30 cases, they were all treated with class Ⅰ agents. The drugs used include: mexiletine (8 cases), moricizine (9), propafenone (12) and apridine (1). GrouP Ⅱ was composed of other 30 patients, and were all treated with amiodarone. The ddlerences of QT intervals between ECG leads (QTd and QTcd) were measured belore and aler medication. Results Before medication, the QTmax and QTcmax in group Ⅱ were signilicantly longer than those of group Ⅰ, resulting in greater QTd and QTcd in grouP Ⅱ (QTd:66± 14ms vs 31± 16ms, P<0.01; QTcd:71±36ms vs 44± 18ms, P<0.01). Alter medication, QTmax and QTcmax of group Ⅰ were prolonged, leading to the lengthening of QTd (from 31±16ms to 45±17ms, P<0.01) and QTcd (from 44± 18 ms to 58± 21ms, P<0.05), indicating the increase of inhomogeneity of myocardial repolarization after the treatment of class Ⅰ agents. Alter amiodarone treatment, QTmin and QTmax in grouP Ⅱ were both prolonged, with a greater amplitude of QTmin prolongation, resulting in decreased QTd and QTcd in group Ⅱ (QTd /rom 66± 14ms to 36±22ms, P<0.01, QTcd from 71±36ms to 45±27ms, P<0.01). The signifcant dofference of QTd and QTcd between two groups disappeared aler medication. Conclusion The results of the present study may relect the opposite effects of amiodarone and these class Ⅰ agents on myocardial repolarization.

Contemporary therapy of atrial fibrillation

Atrial fibrillation (AF) is estimated that by 2010, approximately 2.6 million people will be affected in USA;by 2050, that number may increase to 10 million patients. Generally, rate control alone is reasonable in some AF patients, especially asymptomatic patients. Restoration and maintenance of sinus rhythm (SR) may be achieved by means of cardioversion, drugs or/ and catheter ablation. Pharmacological therapy can be useful to maintain SR and prevent tachycardia-induced cardiomyopathy. All patients with AF regardless of whether a rhythm or rate control strategy recommend anticoagulant, antiplatelet or both combined therapy for prevention of thromboembolism, except those with lone AF or contraindications. Drug selection should be based upon the absolute risk of stroke, bleeding, the relative risk and benefit for a given patient. Biventricular pacing may overcome many of the adverse hemodynamic effects associated with RV pacing alone. A target individual ectopic foci ablation within the pulmonary vein (PV) has evolved to circumferential electrical isolation of the entire PV musculature. Cavotricuspid isthmus should be considered as first-line therapy for patients with typical atrial flutter. Completely non-fluoroscopic ablation guided by Real-Time Magnetic Resonance Imaging (RTMRI) using a steerable and non-ferromagnetic catheter is a promising novel technology in interventional electrophysiology.

Flecainide in Cadaveric Blood and Tissues

In this report, we described a death caused by a deliberate overdose of Flecainide acetate （Almarytm^（R））, an antiarrhythmic agent. The patient had taken a box of 20 Almarytm^（R） 100 mg tablets. The Flecainide concentration found in the post-mortem cardiac blood was 10.16 mg/L. This concentration could not have been determined by post-mortem diffusion of the drug from gastric residue because the patient was previously given activated carbon during the emergency procedure. In fact, in the peripheral blood, the Flecainide concentration was 8.64 mg/L, therefore, this concentration is overlapping with the concentration in the cardiac blood; the gastric content was negative at the screening of Flecainide, while the liver tissue concentration of Flecaiuide was 59.6 mg/L and the bile concentration was 128 mg/L. The brain tissue concentration of Flecainide was 4.19 mg/L. In this case, the cause of death, excluding that toxicity was depending on post-mortem gastric diffusion of the drug, because of the absorbing activity of the administered carbon at the recovery.

Structural characterization,in vivo toxicity and biological activity of two new pyro-type diterpenoid alkaloids derived from 3-acetylaconitine

Objective:The transformations that occur in diterpenoid alkaloids during the process of sand frying for Chinese herbal medicine preparation have yet to be clarified.This study investigated the structural changes that take place in 3-acetylaconitine during a simulation of heat-processing and evaluated the toxicity and biological activity of the pyrolysis products.Methods:The diterpenoid alkaloid 3-acetylaconitine was heated at 180°C for 15 min to simulate the process of sand frying.The pyrolysis products were separated using column chromatography,and their structures were investigated using high-resolution electrospray ionization mass spectroscopy and nuclear magnetic resonance spectroscopy.Further,in vivo cardiotoxicity and acute toxicity of 3-acetylaconitine and its pyrolysis products were compared,and the aconitine-induced arrhythmia model was employed to evaluate the antiarrhythmic effect of the pyrolysis products.Results:Two new diterpenoid alkaloids,pyroacetylaconitine and 16-epi-pyroacetylaconitine,a pair of epimers at C-16,were isolated.After comparing the structures of these compounds,possible transformation pathways were proposed.Compared with the prototype compound,3-acetylaconitine,the cardiotoxicity and acute toxicity of the heat-transformed products were significantly decreased.In the biological activity assay,the two pyrolysis products exhibited an effective increase in ventricular premature beat latency,a reduction in the occurrence of ventricular tachycardia,as well as an increase in the rate of arrhythmia inhibition,implying strong antiarrhythmic activity.Conclusion:Compared with 3-acetylaconitine,its pyrolysis products displayed lower toxicity and good antiarrhythmic effects;thus,they have potential for being developed into antiarrhythmic medicines.

Effects of Chinese herbs on multiple ion channels in isolated ventricular myocytes

Background Shensong Yangxin （SSYX） is one of the compound recipe of Chinese materia medica. This study was conducted to investigate the effects of SSYX on sodium current （/Na）, L-type calcium current （/Ca.L）, transient outward potassium current （/to）, delayed rectifier current （/K）, and inward rectifier potassium currents （/K1） in isolated ventricular myocytes. Methods Whole cell patch-clamp technique was used to study ion channel currents in enzymatically isolated guinea pig or rat ventricular myocytes. Results SSYX decreased peak Na by （44.84±7.65）% from 27.21±5.35 to 14.88±2..75 pA/pF （n=-5, P〈0.05）. The medicine significantly inhibited the /Ca,L. At concentrations of 0.25, 0.50, and 1.00 g/100 ml, the peak/Ca,L was reduced by （19.22±1.10）%, （44.82±6.50）% and （50.69±5.64）%, respectively （n=5, all P〈0.05）. SSYX lifted the I-V curve of both /Na and /Ca,L without changing the threshold, peak and reversal potentials. At the concentration of 0.5%, the drug blocked the transient component of /to by 50.60% at membrane voltage of 60 mV and negatively shifted the inactive curve and delayed the recovery from channel inactivation. The tail current density of /K was decreased by （30.77±1.11）% （n=5, P〈0.05） at membrane voltage of 50 mV after exposure to the medicine and the time-dependent activity of /K was also inhibited. Similar to the effect on /K, the SSYX inhibited /K1 by 33.10% at the test potential of -100 mV with little effect on reversal potential and the rectification property. Conclusions The experiments revealed that SSYX could block multiple ion channels such as /Na /Ca,L, /k, /to and /K1, which may change the action potential duration and contribute to some of its antiarrhythmic effects.

The effects of paeoniflorin monomer of a Chinese herb on cardiac ion channels

Background Because of the potential proarrhythmic effect of current antiarrhythmic drugs, it is still desirable to find safer antiarrhythmic drugs worldwide. Paeoniflorin is one of the Chinese herb monomers that have different effects on many ion channels. The present study aimed to determine the effects of paeoniflorin on cardiac ion channels.Methods Whole-cell patch-clamp technique was used to record ion channel currents. L-type calcium current （/Ca-L）,inward rectifier potassium current （/K1）, and transient outward potassium current （/to1） were studied in rat ventricular myocytes and sodium current （/Na）, slow delayed rectifier current （/Ks）, and HERG current （/Kr） were investigated in transfected human embryonic kidney 293 cells.Results One hundred μmol/L paeoniflorin reduced the peak /ca-L by 40.29% at the test potential of ±10 mV （from （-9.78±0.52） pA/pF to （-5.84±0.89） pA/pF, n=5, P=0.028）. The steady-state activation curve was shifted to more positive potential in the presence of the drug. The half activation potentials were （-11.22±0.27） mV vs. （-5.95±0.84） mV （n=5,P=0.007）, respectively. However, the steady-state inactivation and the time course of recovery from inactivation were not changed. One hundred μmol/L paeoniflorin completely inhibited the peak /Na and the effect was reversible. Moreover,paeoniflorin inhibited the /K1 by 30.13% at the test potential of -100 mV （from （-25.26±8.21） pA/pF to （-17.65±6.52）pA/pF, n=6, F=0.015） without effects on the reversal potential and the rectification property. By contrast, 100 μmol/L paeoniflorin had no effects on/to1, /Ks or /Kr channels.Conclusions The study demonstrated that paeoniflorin blocked /Ca-L, /Na, and /Kf without affecting /to1, /Ks, or /Kr. The multi-channel block effect may account for its antiarrhythmic effects with less proarrhythmic potential.