Cardiac Electrophysiological Differences Between Kunming and C57BL6/J Mice

Objective To investigate the alterations of cardiac electrophysiological properties and substantial mechanism and find the stable arrhythmia mouse model in Kunming(KM) and C57BL6/J(C57) mice.Methods Electrocardiogram recordings were used to analyze the QT interval in vivo,and monophasic action potential of right and left ventricular epicardium was recorded to elicit changes of action potential duration(APD) in conventional and programmed electrical stimulation(PES).Transient outward potassium current(I to) was recorded via whole-cell patch-clamp technique in single right and left epicardial myocytes.Results QT interval was prolonged in KM mice relative to C57 mice(62.51±4.47 ms vs.52.59±4.85 ms,P<0.05).The APD at 50% repolarization of the left ventricular epicardium(18.60±0.91 ms vs.12.90±0.35 ms),and APDs at 50%(17.31±6.05 ms vs.12.00±3.24 ms) and 70% repolarization(36.13±5.32 ms vs.21.95±8.06 ms) of the right ventricular epicardium in KM mice were significantly prolonged compared with C57 mice,respectively(all P<0.05).KM mice were more sensitive to PES-induced ventricular tachycardia(25%,3 of 12 hearts),and especially to Burst-induced ventricular tachycardia(50%,6 of 12 hearts) compared with C57 mice,which were 20%(2 of 10 hearts) and 30%(3 of 10 hearts) respectively.I to densities both in the left and right ventricular epicardial myocytes from KM mice were significantly decreased compared with C57 mice,respectively(all P<0.01).Conclusion Our data showed that KM mice with the prolonged QT interval and APD are vulnerabilities to ventricular arrhythmia,which are attributed to lower I to densities in ventricular myocytes obtained from KM mice than that from C57 mice.

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 Shensong Yangxin on the Progression of Paroxysmal Atrial Fibrillation is Correlated with Regulation of Autonomic Nerve Activity

Background： Shensong Yangxin （SSYX）, a traditional Chinese herbal medicine, has long been used clinically to treat arrhythmias in China. However, the mechanism of SSYX on atrial fibrillation （AF） is unknown. In this study, we tested the hypothesis that the effect of SSYX on the progression of paroxysmal AF is correlated with the regulation of autonomic nerve activity. Methods： Eighteen mongrel dogs were randomly divided into control group （n = 6）, pacing group （n = 6）, and pacing ＋ SSYX group （n = 6）. The control group was implanted with pacemakers without pacing; the pacing group was implanted with pacemakers with long-term intermittent atrial pacing; the pacing ＋ SSYX group underwent long-term intermittent atrial pacing and SSYX oral administration. Results： Compared to the pacing group, the parameters of heart rate variability were lower after 8 weeks in the pacing ＋ SSYX group （low-frequency [LF] component： 20.85± 3.14 vs. 15.3±1.89 ms2, P =0.004; LF component/high-frequency component： 1.34 ± 0.33 vs. 0.77± 0.15, P 〈 0.001 ）. The atrial effective refractory period （AERP） was shorter and the dispersion of the AERP was higher after 8 weeks in the pacing group, while the changes were suppressed by SSYX intake. The dogs in the pacing group had more episodes and longer durations of AF than that in the pacing ＋ SSYX group. SSYX markedly inhibited the increase in sympathetic nerves and upregulation of tumor necrosis factor-alpha and interleukin-6 expression in the pacing ＋ SSYX group. Furthermore, SSYX suppressed the decrease of acetylcholine and α7 nicotinic acetylcholine receptor protein induced by long-term intermittent atrial pacing. Conclusions： SSYX substantially prevents atrial electrical remodeling and the progression of AF. These effects of SSYX may have association with regulating the imbalance of autonomic nerve activity and the cholinergic anti-inflammatory pathway.

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.

Contemporary characteristics,management,and outcomes of patients hospitalized for atrial fibrillation in China:results from the real-world study of Chinese atrial fibrillation registry

Atrial fibrillation(AF)is a growing public health problem in the context of the epidemiologic transition from communicable to non-communicable diseases,and a high prevalence of AF was found in Chinese patients who died in hospital.[1]Indeed,most understanding of AF is based on findings from clinical trials and observational studies performed in North America and Western Europe,[2]and some studies have described the characteristics of patients with AF in other regions.These data have highlighted the important differences in the clinical characteristics and treatment of patients with AF in these regions.[3,4]However,few studies have investigated the characteristics of patients with AF in China.Hence,the aim of this study was to investigate the clinical demographics,management,and outcomes of patients hospitalized for AF using data from a recently registered AF-specific nationwide cohort study in China,the real-world study of Chinese atrial fibrillation(RWS-CAF)registry.The RWS-CAF registry(registration number:ChiCTR1900021250)comprises a multicenter,observational,prospective cohort that includes consecutive patients requiring hospitalization with a diagnosis of AF made according to the Chinese AF guidelines,spanning from November 1,2017,to October 31,2018.All of the enrolled hospitals are grade A class three hospitals.Individual patients hospitalized with AF who were aged 18 years or older were recruited.

Comparative outcomes of subcutaneous and transvenous cardioverter-defibrillators

Background: The comparative outcomes of subcutaneous implantable cardioverter-defibrillator (S-ICD) and transvenous (T-ICD) have not been well studied. The aim of this study was to evaluate the safety and efficacy of currently available S-ICD and T-ICD. Methods: The study included 86 patients who received an S-ICD and 1:1 matched to those who received single-chamber T-ICD by gender, age, diagnosis, left ventricular ejection fraction (LVEF), and implant year. The clinical outcomes and implant complications were compared between the two groups. Results: The mean age of the 172 patients was 45 years, and 129 (75%) were male. The most common cardiac condition was hypertrophic cardiomyopathy (HCM, 37.8%). The mean LVEF was 50%. At a mean follow-up of 23 months, the appropriate and inappropriate ICD therapy rate were 1.2% vs. 4.7%(X^2= 1.854, P=0.368) and 9.3% vs. 3.5%(X^2 = 2.428, P = 0.211) in S-ICD and T-ICD groups respectively. There were no significant differences in device-related major and minor complications between the two groups (7.0% vs. 3.5%, X^2 = 1.055, P = 0.496). The S-ICD group had higher T-wave oversensing than T-ICD group (9.3% vs. 0%, X^2 = 8.390, P=0.007). Sixty-five patients had HCM (32 in S-ICD and 33 in T-ICD). The incidence of major complications was not significantly different between the two groups. Conclusions: The efficacy of an S-ICD is comparable to that of T-ICD, especially in a dominantly HCM patient population. The S-ICD is assodated with fewer major complications demanding reoperation.