Effects of dagliflozin on atrial tachyarrhythmia in rats with pulmonary arterial hypertension related right heart failure and its mechanisms / 中国药理学通报

Aim To investigate the effects of dagliflozin (DAPA) on atrial tachyarrhythmia (AT) in rats with right heart failure (RHF) due to pulmonary arterial hypertension (PAH) and the underlying mechanisms. Methods Sixty male SD rats were randomly divided into four groups: control group (CTL group), model group (MCT group), MCT + low-dose DAPA intervention group (MCT + LD group) and MCT + high-dose DAPA intervention group (MCT + HD group). After 35 days of continuous intervention, the model and cardiac function evaluation, atrial structural remodelling assessment, inflammatory factor detection, and in vivo cardiac electrophysiology experiments were completed. Results DAPA reduced menn pulmonaryarterial pressure (mPAP) and menn right ventricular pressure (mRVP) in the model rats (P <0.05), attenuated the inflammatory response (P < 0.05), reduced right atrial fibrosis (P <0.05), reduced AT induction rate (P < 0.05) and mean atrial tachyarrhythmia duration (MATD) (P < 0.05), the extent of which was more pronounced in the high-dose DAPA intervention group. Conclusions DAPA can reduce AT susceptibility in PAH-induced RHF rats, and the mechanisms may be related to the inhibition of systemic inflammation and anti-atrial fibrosis by DAPA.

Effect of Shensong Yangxin on the Progression of Paroxysmal Atrial Fibrillation is Correlated with Regulation of Autonomic Nerve Activity / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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 ms 2 , 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.</p><p><b>CONCLUSIONS</b>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.</p>

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 / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>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).</p><p><b>METHODS</b>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).</p><p><b>RESULTS</b>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 LVEF, NYHA classification, NT-proBNP, 6MWD, and MLHFQ scores showed a greater improvements in the SSYX group than in the placebo group (ΔLVEF 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]; Δ6MWD at 12th week: 35.1 ± 38.6 vs. 17.2 ± 45.6; ΔMLHFQ at the 4th, 8th, and 12th week: -4.24 ± 6.15 vs. -2.31 ± 6.96, -8.19 ± 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.</p><p><b>CONCLUSIONS</b>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.</p><p><b>TRIAL REGISTRATION</b>www.chictr.org.cn, ChiCTR-TRC-12002061 (http://www.chictr.org.cn/showproj.aspx?proj=7487) and Clinicaltrials.gov, NCT01612260 (https://clinicaltrials.gov/ct2/show/NCT01612260).</p>

A cross-sectional survey on the prevalence of anxiety symptoms in Chinese patients with premature ventricular contractions without structural heart disease / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Anxiety appears to be more common in patients with coronary artery disease (CHD) than in the general population, and anxiety symptoms may precede onset of CHD and play an important role in development of CHD. Little is known about the prevalence of anxiety symptoms in Chinese patients with premature ventricular contractions (PVCs). Our objective was to study anxiety symptoms and potential risk factors in a Chinese population with PVCs but without structural heart disease.</p><p><b>METHODS</b>The Zung self-rating anxiety scale (ZSAS) was used to assess anxiety symptoms. Correlation between anxiety symptoms and socio-demographics and medical factors were analyzed by Logistic regression.</p><p><b>RESULTS</b>Of 1144 patients with PVCs (487 males and 657 females), age (53 ± 23) years old, disease duration 1 month to 24 years, a total of 381 (33.3%) patients were categorized as having anxiety symptoms. Anxiety symptoms increased with age, low income, low education level, nationality, PVC count/24 hours, bad social support, village settlement type (P < 0.05). Multivariate Logistic regression indicated that six variables-education level, ethnic minorities, dwelling place, age, PVC count/24 hours, and social support-significantly and independently related with anxiety symptoms (P < 0.05).</p><p><b>CONCLUSIONS</b>In the Chinese population, anxiety symptoms in subjects with PVCs were frequent. Education level, ethnic minorities, dwelling place, age, PVC count/24 hours, and social support were independent risk factors for anxiety symptoms. Further research on the relationship between PVCs and anxiety symptoms in China is necessary.</p>

Construction of fusion gene vaccine of WT1 multi-epitope fused with stimulating epitope of mycobacterium tuberculosis heat shock protein 70 and its expression and immunogenicity / 中国实验血液学杂志

This study was purposed to construct a fusion DNA vaccine containing WT1 multi-epitope and stimulating epitope of mycobacterium tuberculosis heat shock protein 70 and to detect its expression and immunogenicity. On the basis of published data, a multi-epitope gene (Multi-WT1) containing three HLA *0201-restricted CTL epitopes: one HLA*2402-restricted CTL epitope, two Th epitopes and one universal Th Pan-DR epitope (PADRE) was constructed. DNA-coding sequence was modified by Computer-Aided Design (CAD) to optimize proteasome-mediated epitope processing through the introduction of different amino acid spacer sequences. The synthetic nucleotide sequence was then inserted into an eukaryotic vector to construct the plasmid pcDNA3.1-WT1.For enhancing CTL activity, HSP70 fragment including stimulatory domain P407-426 was amplified by PCR from mycobacterial HSP70 gene and cloned into pcDNA3.1(+). Then Multi-WT1 was fused to the N-terminal of pcDNA3.1-mHSP70(407-426) to make the multi-epitope fusion gene vaccine pcDNA3.1-WT1-mHSP70(407-426). HEK-293T cells were transfected with this vaccine and the expressed product was identified by RT-PCR. Enzyme-linked immunospot assay (ELISPOT) was used to evaluate the immunological responses elicited by vaccine. The results showed that the most of WT1 epitopes could be correctly cleaved which was confirmed by software Net Chop 3.1 and PAPROCIanalysis. RT-PCR showed correct expression of target gene in HEK293T cells and ELISPOT showed specific T-cell responses. It is concluded that the eukaryotic expression vector PcDNA3.1-WT1-mHSP70(407-426) fusion gene has been successfully constructed and the immunity response is also elicited, which is a good candidate for further research of DNA vaccine.

Mitral isthmus ablation in patients with prosthetic mitral valves / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Previous studies have investigated the technique of linear ablation at the mitral isthmus (MI) in patients with idopathic atrial fibrillation (AF), but MI ablation in patients with prosthetic natural mitral valves (MVs) was not described in detail. Present study sought to summarize our initial experience of ablating MI in patients with prosthetic MVs</p><p><b>METHODS</b>Patients with drug refractory AF and prosthetic MVs were eligible for this study, and the patients with natural MVs but received MI ablation served as control group. Left atrium (LA) mapping and ablation was carried out guided by CARTO system. The anatomy of MI was assessed via computer topography scan.</p><p><b>RESULTS</b>During the study period, a consecutive of 19 patients (male/female = 12/7, mean age of (48 ± 6) years) with prosthetic MVs (16 with metal valves, 3 with biologic valves) entered for AF ablation, other 35 patients served as control group. In study group, mapping along MI documented lower voltages ((2.0 ± 1.0) vs. (3.1 ± 1.3) mV, P = 0.002), more fragmented potentials (19/19 vs. 20/15, P < 0.001), and higher impedance ((132 ± 34) vs. (110 ± 20) Ω, P = 0.004). After initial ablation, more residual gaps along the MI lesions were found in study group (2.4 ± 0.4 vs. 1.7 ± 0.3, P < 0.001). The mean length of MI ((6.2 ± 3.3) vs. (7.1 ± 2.3) cm, P = 0.25) was comparable between 2 groups, but the MI in study group was much thicker ((3.1 ± 1.8) vs. (2.1 ± 1.07) cm, P = 0.01) and all were found as pouch type (19/19 vs. 2/35, P < 0.001). The follow-up results were comparable (65.1% vs. 72.3%, P = 0.30).</p><p><b>CONCLUSION</b>For patients with prosthetic MVs, linear ablation at MI could be successfully carried out despite anatomical and pathological changes.</p>

Curcumin attenuates left ventricular dysfunction and remodeling in rabbits with chronic heart failure / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the effects of Curcumin on rabbits with chronic heart failure.</p><p><b>METHODS</b>Heart failure was induced by combined aortic regurgitation and aortic stenosis in 20 New Zealand rabbits and treated with placebo (HF, n = 10) and Curcumin (Cur, 100 mgxkg(-1)xd(-1), n = 10) for 8 weeks, 10 sham operated rabbits served as controls (Con). Echocardiography was performed in all rabbits at baseline and 8 weeks later. Aortic diameter (AO), left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS), left ventricular end-systolic dimension (LVDs), left ventricular end-diastolic dimension (LVDd), left ventricular posterior wall thickness (LVPW) and interventricular septum thickness (IVS) were measured. Myocardial matrix metalloproteinase (MMP)-2 and MMP-9 expressions and fibrosis were determined by immunohistochemistry and Masson staining respectively.</p><p><b>RESULTS</b>Compared to baseline, LVEF and LVFS were significantly decreased, AO, LVDs, LVDd, LVPW, and IVS significantly increased at 8 weeks after operation in HF group while these changes could be significantly attenuated in Curcumin treated rabbits. The protein expressions of MMP-2 and MMP-9 were significantly down-regulated in HF group and could be significantly up-regulated by Curcumin treatment. The increased collagen deposition in HF group was also significantly reduced by Curcumin treatment.</p><p><b>CONCLUSION</b>Curcumin attenuated left ventricular dysfunction and remodeling by up-regulating MMPs expressions and reducing myocardial fibrosis.</p>

Effects of NADPH oxidase inhibition on cardiac function and myocardial calcium regulatory proteins in rabbits with heart failure / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the effects of NADPH oxidase inhibition on cardiac function and myocardial calcium regulatory proteins mRNA expressions in rabbits with heart failure (HF).</p><p><b>METHODS</b>HF was induced by experimental aortic insufficiency and abdominal aortic constriction, HF animals were treated with oral apocynin (15 mg/d), a NADPH oxidase inhibitor or equal dose placebo. Eight weeks later, cardiac function was measured by echocardiography. Myocardial NADPH oxidase activity was evaluated by NADPH dependent superoxide production examined using superoxide dismutase-inhibitable cytochrome c reduction. Sarcoplasmic reticulum Ca(2+)ATPase (SERCA2a), ryanodine receptor 2 (RyR2), phospholamban (PLB) and sodium-calcium exchanger (NCX) were determined by RT-PCR.</p><p><b>RESULTS</b>Rabbits with HF developed ventricular dilatation and cardiac dysfunction, as well as increase in myocardial NADPH oxidase activity, decreases in mRNA expression of SERCA2a, RyR2 and PLB, and increase in mRNA expression of NCX. Apocynin significantly reduced NADPH oxidase activity (P < 0.05), upregulated SERCA2a, RyR2 and PLB mRNA expressions (SERCA2a/GAPDH: 0.63 +/- 0.11 vs. 0.34 +/- 0.08, RyR2/GAPDH: 0.23 +/- 0.04 vs. 0.17 +/- 0.06, PLB/GAPDH:1.28 +/- 0.13 vs. 0.95 +/- 0.09, P < 0.05), downregulated NCX mRNA expression (NCX/GAPDH: 0.67 +/- 0.10 vs. 0.95 +/- 0.12, P < 0.05), and improved cardiac function [LVEF: (60.06 +/- 10.07)% vs. (38.87 +/- 3.31)%, LVFS: (30.12 +/- 6.56)% vs. (17.40 +/- 2.45)%, P < 0.05] in rabbits with HF.</p><p><b>CONCLUSION</b>NADPH oxidase inhibition improves cardiac function possibly by preventing abnormal alterations in myocardial calcium regulatory proteins in failing heart.</p>

Sinus node, phrenic nerve and electrical connections between superior vena cava and right atrium: lessons learned from a prospective study / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>When performing superior vena cava isolation, the major concerns are inadvertent ablation on sinus node and right phrenic nerve. However, little is known about the spatial relationship of electrical connections between superior vena cava and right atrium with the sinus node and phrenic nerve locations among individual patients.</p><p><b>METHODS</b>We studied 87 patients (male/female 60/27, mean age of (51 +/- 9) years) with atrial fibrillation. Before superior vena cava isolation, the sinus node site was defined by right atrium activation mapping during sinus rhythm and the right phrenic nerve site was localized via pacing manoeuvre. Superior vena cava was isolated by ablation at the electrical connection under the guidance of circular mapping catheter. The sites of sinus node, phrenic nerve and electrical connections were noted. Continuous variables were compared using Student's t test. A P value < 0.05 was considered statistically significant.</p><p><b>RESULTS</b>Right atrium activation mapping revealed that the sinus node located at the anterior lateral segment of superior vena cava-right atrium junction in all patients. In 82 patients with detectable diaphragmatic stimulations, the phrenic nerve sites were predominantly at the lateral segment (70/82) with anterior lateral and anterior segments for a few patients. A total of 165 electrical connections were located among all 87 patients, and this averaged 1.8 +/- 0.6 (1-3) per patient. The anterior septum (72 patients (43.6%)), the anterior wall (40 (24.2%)), and the posterior septum (35 (35.4%)) of superior vena cava-right atrium junction were the electrical connection regular sites. Superior vena cava was isolated in all patients. Two patients developed sinus bradycardia, with 3 mild superior vena cava stenosis and 2 phrenic nerve palsy.</p><p><b>CONCLUSIONS</b>The sinus node, phrenic nerve and electrical connection sites were distributed along the superior vena cava-right atrium junctions at expected locations for most patients. The electrical connections were separated from the sinus node and phrenic nerve sites. With the activation mapping of right atrium and pacing along superior vena cava-right atrium junctions, the sinus node and phrenic nerve were localized and superior vena cava isolated in most patients.</p>

Increased expression of transient receptor potential melastatin 7 in mouse cardiac fibroblasts post myocardial infarction / 中华心血管病杂志

<p><b>OBJECTIVE</b>To observe transient receptor potential melastatin 7-like (TRPM7L) expression changes post myocardial infarction (MI) in mouse cardiac fibroblast (CF).</p><p><b>METHODS</b>TRPM7 expression and Ca2+ influx in CF from MI and control mice were quantified by mRNA RT-PCR and whole cell patch clamp technique.</p><p><b>RESULTS</b>(1) TRPM7 expression was significantly upregulated post MI and Ca2+ influx of CF were significantly increased post MI [(7.4 +/- 0.7) pA/pF vs. (16.2 +/- 1.7) pA/pF, P < 0.01] and Ca2+ influx of CF increased 3-fold under lower pH condition; (2) These effects could be blocked by knock-out TRPM7 gene with SiRNA.</p><p><b>CONCLUSION</b>TRPM7L upregulation post MI and under lower pH condition are responsible for increased Ca2+ influx in CF.</p>

The prevalence of J wave in apparently healthy subjects in Hubei province of China / 中华心血管病杂志

<p><b>OBJECTIVE</b>To observe the prevalence of J wave in apparently healthy subjects in Wuhan.</p><p><b>METHODS</b>The study subjects comprised of 1817 apparently healthy subjects (1131 males, mean age 46.38 +/- 15.81 years; 686 females, mean age was 42.77 +/- 14.15 years). ECG and routine medical examinations were performed. J wave was defined as a wave followed QRS complexes with amplitude of at least 0.05 mV and 0.03 s.</p><p><b>RESULTS</b>The overall incidence of J wave was 7.26%. The incidence of J wave in males was significantly higher than in females (10.53% vs. 1.87%, P < 0.01). The incidence of J wave in leads of inferior wall (II, III, avF), right wall (V(1 - 3)) and left wall (V(4 - 6)) was 4.57%, 0.50%, and 2.20%, respectively. J wave located in leads of inferior wall was more than in left and right walls (both P < 0.05). The incidence of J wave positively correlated with age (y = 0.1387x + 1.6318, r = 0.78, P < 0.01).</p><p><b>CONCLUSIONS</b>J wave is more likely seen in males and aged people and is more likely located in leads of inferior wall, than in leads of left and right walls.</p>

Effect of carvedilol on distribution and expression of connexin43 / 中华急诊医学杂志

Objective To observe the effect of carvedilol on the expression of Cx43 in rabbits with myocardial infarction and its association with ventricular arrhythmia.Method Thirty-six rabbits were randomly divided into three groups in equal number(n=12),namely,myocardial infarction(MI)group,carvedilol group and sham MI group.Rabbits of carvedilol group were administered with carvedilol 5 mg kg~(-1)?d~(-1)after MI induced,while no carvedilol was administered to the MI group.The following observations were made:(1)Cx43 density of the epicardial border zone measured by quantitative immnuoconfocal laser scanning,and(2)cx43 protein expression analyzed by western blot.Results(1)Under immunoconfocal laser microscope,the relative density of Cx43 was(0.16?0.06)% in the infarction group and was(0.32?0.11)% in the sham MI group [(0.68?0.15)%,both P

Changes of IK, ATP current density and allosteric modulation during chronic atrial fibrillation / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Atrial fibrillation (AF) is the most common supraventricular arrhythmia in clinical practice. Chronic atrial fibrillation (CAF) is associated with ionic remodeling. However, little is known about the activity of ATP-sensitive potassium current (IK, ATP) during CAF. So we studied the changes of IK, ATP density and allosteric modulation of ATP-sensitivity by intracellular pH during CAF.</p><p><b>METHODS</b>Myocardium samples were obtained from the right auricular appendage of patients with rheumatic heart disease complicated with valvular disease in sinus rhythm (SR) or CAF. There were 14 patients in SR group and 9 patients in CAF group. Single atrial cells were isolated using an enzyme dispersion technique. IK, ATP was recorded using the whole-cell and inside-out configuration of voltage-clamp techniques. In whole-cell model, myocytes of SR and CAF groups were perfused with simulated ischemic solution to elicit IK, ATP. In inside-out configuration, the internal patch membranes were exposed to different ATP concentrations in pH 7.4 and 6.8.</p><p><b>RESULTS</b>Under simulated ischemia, IK, ATP current density of CAF group was significantly higher than in SR group [(83.5 +/- 10.8) vs. (58.7 +/- 8.4) pA/pF, P < 0.01]. IK, ATP of the two groups showed ATP concentration-dependent inhibition. The ATP concentration for 50% current inhibition (IC50) for the SR group was significantly different in pH 7.4 and pH 6.8 (24 vs. 74 micromol/L, P < 0.01). The IC50 did not change significantly in CAF group when the pH decreased from 7.4 to 6.8.</p><p><b>CONCLUSIONS</b>During CAF, IK, ATP current density was increased and its allosteric modulation of ATP-sensitivity by intracellular pH was diminished.</p>

Effects of rehabilitation training on endothelial function and collateral circulation in patients underwent PCI / 中华物理医学与康复杂志

Objective To investigate the effects of rehabilitation and exercise training on endothelial func- tion and collateral circulation in patients with coronary heart disease(CHD)who underwent PCI.Methods Sixty- three cases were divided into three groups:group A undertook rehabilitation protocol with three stages,group B with additional extracorporeal counterpulsation in addition to the intervention of group A,group C acted as control.The Bruce submaximal treadmill,coronary angiography and Doppler were conducted for evaluation of the functional per- formance,lateral branching and endothelium function.Results(1)The value of RPP and RPE of groups A and B were significantly higher than those of the control group as quantified by exercise test alter the third stage of rehabilita- tion(P