Analysis on the Effects of Shensong Yangxin Capsules and Amiodarone on Heart Rate Variability Indices and Inflammatory Factors in Patients with Arrhythmia

Objective:To study the effects of Shensong Yangxin capsules and amiodarone on heart rate variability indexes and inflammatory factors in the treatment of patients with arrhythmia.Methods:The research subjects were selected patients with arrhythmia admitted in our hospitaFs department from October 2018 to October 2019,and a total of 70 patients were divided into two groups.35 subjects in the control group were treated with amiodarone alone,and 35 subjects in the observation group were treated with Shensongyangxin capsule in combination with amiodarone for comparisons in treatment effects,heart rate variability indices,inflammatory factors,and adverse reactions.Results:After observation,the treatment efficiency in the observation group was higher than that in the control group(P<0.05).Before treatment,there was no difference in heart rate variability indices between the two groups(P>0.05),after treatment,the improvement in patients of the observation group was better than that of the control group(P<0.05).After treatment,the inflammatory factors of the two groups of patients decreased,and the indicators of the observation group were comparably lower than those of the control group(P<0.05).In the comparison of adverse reactions,the observation group showed a lower incidence of adverse reactions after treatment than the control group(P<0.05).Conclusion:In the treatment of patients with arrhythmia,the combined use of Shensong Yangxin capsules and amiodarone has more significant therapeutic effects,which can effectively improve the patient's heart rate variability indices,reduce the inflammatory factors,and relieve the symptoms in patients.The incidence of adverse reactions is low and the safety is quite high,therefore it has great value in clinical applications.

Effects of Traditional Chinese Medicine Shensong Yangxin Capsules on Heart Rhythm and Function in Congestive Heart Failure Patients with Frequent Ventricular Premature Complexes：A Randomized, Double-blind, Multicenter Clinical Trial

Background：Pharmacological therapy for congestive heart failure （CHF） with ventricular arrhythmia is limited.In the study,our aim was to evaluate the effects of Chinese traditional medicine Shensong Yangxin capsules （SSYX） on heart rhythm and function in CHF patients with frequent ventricular premature complexes （VPCs）.Methods：This double-blind,placebo-controlled,multicenter study randomized 465 CHF patients with frequent VPCs to the SSYX （n =232） and placebo groups （n =233） for 12 weeks of treatment.The primary endpoint was the VPCs monitored by a 24-h ambulatory electrocardiogram.The secondary endpoints included the left ventricular ejection fraction （LVEF）,left ventricular end-diastolic diameter,N-terminal pro-brain natriuretic peptide （NT-proBNP）,New York Heart Association （NYHA） classification,6-min walking distance （6MWD）,Minnesota Living with Heart Failure Questionnaire （MLHFQ） scores,and composite cardiac events （CCEs）.Results：The clinical characteristics were similar at baseline.SSYX caused a significantly greater decline in the total number of VPCs than the placebo did （-2145 ± 2848 vs.-841 ± 3411,P 〈 0.05）.The secondary endpoints of the LVEE NYHA classification,NT-proBNP,6MWD,and MLHFQ scores showed a greater improvements in the SSYX group than in the placebo group （ALVEF at 12th week：4.75 ± 7.13 vs.3.30 ± 6.53;NYHA improvement rate at the 8th and 12th week：32.6% vs.21.8%,40.5% vs.25.7%;mean level of NT-proBNP in patients with NT-proBNP 〉125 pg/ml at 12th week：-122 [Q1,Q3：-524,0] vs.-75 [Q1,Q3：-245,0];A6MWD at 12th week：35.1 ± 38.6 vs.17.2 ± 45.6;AMLHFQ at the 4th,8th,and 12th week：-4.24 ± 6.15 vs.-2.31 ± 6.96,-8.l 9 ± 8.41 vs.-3.25 ± 9.40,10.60 ± 9.41 vs.-4.83 ± 11.23,all P 〈 0.05）.CCEs were not different between the groups during the study period.Conclusions：In this 12-week pilot study,SSYX was demonstrated to have the benefits of VPCs suppression and cardiac function improvement with good compliance on a background of standard treatment for CHF.

Effect of the Shensong Yangxin Capsule on Energy Metabolism in Angiotensin II-lnduced Cardiac Hypertrophy

Background：Shensong Yangxin Capsule （SSYX）,traditional Chinese medicine,has been used to treat arrhythmias,angina,cardiac remodeling,cardiac fibrosis,and so on,but its effect on cardiac energy metabolism is still not clear.The objective of this study was to investigate the effects of SSYX on myocardium energy metabolism in angiotensin （Ang） Ⅱ-induced cardiac hypertrophy.Methods：We used 2 μl （10-6 mol/L） AngⅡ to treat neonatal rat cardiomyocytes （NRCMs） for 48 h.Myocardial α-ac tinin staining showed that the myocardial cell volume increased.Expression of the cardiac hypertrophic marker-brain natriuretic peptide （BNP） messenger RNA （mRNA） also increased by real-time polymerase chain reaction （PCR）.Therefore,it can be assumed that the model of hypertrophic cardiomyocytes was successfully constructed.Then,NRCMs were treated with 1 μl of different concentrations of SSYX （0.25,0.5,and 1.0 μg/ml） for another 24 h.To explore the time-depend effect of SSYX on energy metabolism,0.5 μg/ml SSYX was added into cells for 0,6,12,24,and 48 h.Mitochondria was assessed by MitoTracker staining and confocal microscopy.mRNA and protein expression of mitochondrial biogenesis-related genes-Peroxisome proliferator-activated receptor-γ coactivator-1 α （PGC-1 α）,energy balance key factor -adenosine monophosphate-activated protein kinase （AMPK）,fatty acids oxidation factor-camitine palmitoyltransferase-1 （CPT-1）,and glucose oxidation factor-glucose transporter-4 （GLUT-4） were measured by PCR and Western blotting analysis.Results：With the increase in the concentration of SSYX （from 0.25 to 1.0 μg/ml）,an increased mitochondrial density in Angll-induced cardiomyocytes was found compared to that of those treated with Angll only （0.25 μg/ml,18.3300 ± 0.8895 vs.24.4900 ± 0.9041,t =10.240,P 〈 0.0001;0.5 μg/ml,18.3300 ± 0.8895 vs.25.9800 ± 0.8187,t =12.710,P 〈 0.0001;and 1.0 μg/ml,18.3300 ± 0.8895 vs.24.2900 ± 1.3120,t =9.902,P 〈 0.0001;n =5 per dosage group）.SSYX also increased the mRNA and protein expression ofPGC-1α （0.25 μg/ml,0.8892 ± 0.0848 vs.1.0970 ± 0.0994,t =4.319,P =0.0013;0.5 μg/ml,0.8892 ± 0.0848 vs.1.2330 ± 0.0564,t =7.150,P 〈 0.0001;and 1.0 μg/ml,0.8892 ± 0.0848 vs.1.1640 ± 0.0755,t =5.720,P 〈 0.0001;n =5 per dosage group）,AMPK （0.25 μg/ml,0.8872 ± 0.0779 vs.1.1500 ± 0.0507,t =7.239,P 〈 0.0001;0.5 μg/ml,0.8872 ± 0.0779 vs.1.2280 ± 0.0623,t =9.379,P 〈 0.0001;and 1.0 μg/ml,0.8872 ± 0.0779 vs.1.3020 ± 0.0450,t =11.400,P 〈 0.0001;n =5 per dosage group）,CPT-1 （1.0 μg/ml,0.7348 ± 0.0594 vs.0.9880 ± 0.0851,t =4.994,P =0.0007,n =5）,and GLUT-4 （0.5 μg/ml,1.5640 ± 0.0599 vs.1.7720 ± 0.0660,t =3.783,P =0.0117;1.0 μg/ml,1.5640 ± 0.0599 vs.2.0490 ± 0.1280,t =8.808,P 〈 0.0001;n =5 per dosage group）.The effect became more obvious with the increasing concentration of SSYX.When 0.5 μg/ml SSYX was added into cells for 0,6,12,24,and 48 h,the expression of AMPK （6 h,14.6100 ± 0.6205 vs.16.5200 ± 0.7450,t =3.456,P =0.0250;12 h,14.6100 ± 0.6205 vs.18.3200 ± 0.9965,t =6.720,P 〈 0.0001;24 h,14.6100 ± 0.6205 vs.21.8800 ± 0.8208,t =13.160,P 〈 0.0001;and 48 h,14.6100 ± 0.6205 vs.23.7400 ± 1.0970,t =16.530,P 〈 0.0001;n =5 per dosage group）,PGC-1α （12 h,11.4700 ± 0.7252 vs.16.9000 ± 1.0150,t =7.910,P 〈 0.0001;24 h,11.4700 ± 0.7252 vs.20.8800 ± 1.2340,t =13.710,P 〈 0.0001;and 48 h,11.4700 ± 0.7252 vs.22.0300 ± 1.4180,t =15.390;n =5 per dosage group）,CPT-1 （24 h,15.1600 ± 1.0960 vs.18.5800 ± 0.9049,t =6.048,P 〈 0.0001,n =5）,and GL UT-4 （6 h,10.2100 ± 0.9485 vs.12.9700 ± 0.8221,t =4.763,P =0.0012;12 h,10.2100± 0.9485 vs.16.9100± 0.8481,t=1 1.590,P〈 0.0001;24 h,10.2100±0.9485 vs.19.0900± 0.9797,t=15.360,P〈 0.0001;and 48 h,10.2100 ± 0.9485 vs.14.1900 ± 0.9611,t =6.877,P 〈 0.0001;n =5 per dosage group） mRNA and protein increased gradually with the prolongation of drug action time.Conclusions：SSYX could increase myocardial energy metabolism in AngⅡ-induced cardiac hypertrophy.Therefore,SSYX might be considered to be an alternative therapeutic remedy for myocardial hypertrophy.

Effects of Shensong Yangxin capsule on pacemaker channels encoded by human HCN4 gene

Shensong Yangxin （SSYX） is one of the compound recipes of Chinese materia medica including 12ingredients such as Panax ginseng, dwarf lilyturf tuber,nardostachys root, etc. Small-scale randomized multi-centre clinical trials suggested that SSYX reduced the number of ventricular extrasystoles in patients with or without structural heart disease.1 Besides excellent antiarrhythmic efficacy,2 SSYX also improved bradycardia in some patients, which was evidenced by animal studies3 as well.

Chinese Medicine Shensong Yangxin Capsule(参松养心胶囊)Ameliorates Myocardial Microcirculation Dysfunction in Rabbits with Chronic Myocardial Infarction

Objective:To investigate the effect of Chinese compound Shensong Yangxin Capsule(参松养心胶囊,SSYX)on myocardial microcirculation in myocardial-infarcted rabbits.Methods:Myocardial infarction(MI)was established in rabbits by ligation of the left circumflex coronary.Thirty rabbits were randomly divided into the control group,the MI group(model),and the MI treated with SSYX group(MI+SSYX)by a random number table method.After 4 weeks of administration,low-energy real-time myocardial contrast echocardiography(RT-MCE)was conducted to assess the microcirculatory perfusion.Immunofluorescence double staining was used to detect the capillary density.The endothelial ultrastructure was observed with a transmission electron microscope.The m RNA expression levels of vascular endothelial growth factor(VEGF),endothelin 1(ET-1),prostaglandin I2(PGI2)and endothelial nitric oxide synthase(e NOS)were measured by real-time quantitative polymerase chain reaction(Real-time PCR).The plasmic levels of ET-1,thromboxane A2(TXA2),nitric oxide(NO)and von willebrand factor(v WF)were examined with enzyme-linked immunosorbent assays(ELISA).Results:SSYX significantly improved the myocardial blood volume,myocardial micro bubble velocity,and myocardial inflow according to the examination of RT-MCE,and it visibly ameliorated the capillary endothelial structure.Furthermore,compared with the MI group,the plasma levels of TXA2,ET-1 and v WF contents significantly decreased in the MI+SSYX group,and the ET-1 mRNA expression levels of myocardium in the border zone significantly decreased,and the VEGF,PGI2 and e NOS m RNA expression levels significantly increased(all P<0.05).Conclusions:SSYX has favorable advantages in ameliorating the impaired myocardial microcirculation following MI.The mechanisms of the effect are related to the ability of SSYX in balancing the endothelial-derived vasodilators and vasoconstrictors,and up-regulating the expression of VEGF and e NOS.

Simultaneous Determination of Eight Bioactive Constituents in Shensong Yangxin Capsule by UPLC

Objective To develop a ultra performance liquid chromatography(UPLC) method for the quality evaluation of Shensong Yangxin Capsule(SYC).Methods The Waters Acquity UPLC HSS T3 column(100 mm × 2.1 mm,1.8μm) was used.Acetonitrile and water containing 0.1% phosphoric acid were used as mobile phases of UPLC with gradient elution.The detection wavelengths were set at 203(ginsenoside Rb1),286(salvianolic acid B),230(paeoniflorin),221(schisantherin A),280(sodium danshensu),327(chlorognenic acid),335(spinosin),and 345nm(berberine hydrochloride),respectively.The flow rate was set at 0.4 mL/min and column temperature was 35 ℃.Results The contents of paeoniflorin,salvianolic acid B,schisantherin A,sodium danshensu,chlorognenic acid,spinosin,berberine hydrochloride,and ginsenoside Rb1were determined from 10 batches of SYC.Conclusion The method of the quality evaluation of SYC has acceptable precision,reproducibility,and stability,which could be used as a new method for the quality control of SYC.

A pilot study of traditional Chinese medicine Shensong Yangxin capsule in patients with premature ventricular contractions and bradycardia

Background Management of premature ventricular contractions （PVCs） and bradycardia is difficult, because most antiarrhythmic drugs may lead to more severe bradycardia, so other effective drugs with less side effects are alternatives for treating those patients. To evaluate the efficacy and safety of the traditional Chinese medicine Shensong Yangxin capsule （SYC） in patients with bradycardia and PVCs, a pilot study was conducted. Methods One hundred and sixty-eight patients with bradycardia and PVCs were randomly assigned to receive either SYC （trial group, = 86） or placebo （control group, = 82） for 4 weeks. ECG, 24-hour continuous ECG recording, echocardiography, quality of life, hepatic function and renal were evaluated at baseline and after 4-week treatment. Results The average heart rate, the fastest heart rate, and the lowest heart rate in the trial group were all significantly higher than those in the baseline and the control group after 4-week follow-up （ 〈 0.01, 0.05, 0.05, respectively.）. Compared with pretreatment, the PVCs in the trial group decreased significantly after treatment （1911.7 ±402.6 vs. 5550.1 ± 973.7, 〈 0.01）. Both the quality of life and the symptom scores in the trial group were significantly better than those in the control group. No severe adverse effects were reported. Conclusion SYC is effective and safe for the treatment of PVCs and bradycardia and improves the symptoms and quality of life.

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.