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Background Implantable cardioverter defibrillators (ICDs) have become the standard approach for prevention of sudden cardiac death. Whether ICD therapy is an independent predictor of all-cause mortality is controversial. We made the systematic review and meta-analysis to estimate the impact of ICD therapy on mortality. Methods We searched the PubMed and Embase databases for studies evaluating the effect of ICD shocks or antitachycardia pacing (ATP) on mortality. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using random effects models. Results Thirteen cohort studies were identified. Mean ejection fraction of the population was 23–35%; 68.0% had ischemic etiology, and 74.5% received a primary prevention ICD implantation. Appropriate shocks were an independent predictor of increased mortality compared with no-shock or no-therapy patients (HR 2.07, 2.76, respectively). In contrast, inconsistent results were obtained during inappropriate-shock analyses: when compared with no-shock patients, inappropriate shocks were associated with an increased risk of death (HR 1.54, 95% CI: 1.25–1.89, P < 0.0001); however, when compared to no-therapy patients, there was no relationship between inappropriate shocks and mortality (HR 1.20, 95% CI: 0.90–1.61, P = 0.22). Subgroup analysis in heart failure patients also did not find any difference in mortality between inappropriate-shock and no-therapy patients. No increased risk of mortality was found in the patients who experienced appropriate or inappropriate ATP only. Conclusion Appropriate shocks were associated with an increased mortality in ICD patients. However, whether inappropriate shocks worsened the clinical outcome was controversial, and larger prospective trials are needed to clarify the issue.

Pepper, a daily-used seasoning for promoting appetite, is widely used in folk medicine for treating gastrointestinal diseases. Piperine is the major alkaloid in pepper and possesses a wide range of pharmacological activities. However, the mechanism for linking metabolic and medicinal activities of piperine remains unknown. Here we report that piperine robustly boosts mTORC1 activity by recruiting more system L1 amino acid transporter (SLC7A5/SLC3A2) to the cell membrane, thus promoting amino acid metabolism. Piperine-induced increase of mTORC1 activity in resident peritoneal macrophages (pMΦs) is correlated with enhanced production of IL-6 and TNF-α upon LPS stimulation. Such an enhancement of cytokine production could be abrogated by inhibitors of the mTOR signaling pathway, indicating mTOR's action in this process. Moreover, piperine treatment protected resident pMΦs from bacterium-induced apoptosis and disappearance, and increased their bacterial phagocytic ability. Consequently, piperine administration conferred mice resistance against bacterial infection and even sepsis. Our data highlight that piperine has the capacity to metabolically reprogram peritoneal resident macrophages to fortify their innate functions against bacterial infection.

The anti-inflammatory effect of piperine has been largely investigated in macrophages, but its activity on epithelial cells in inflammatory settings is unclear. The present study aimed to investigate the effect of piperine on the expression of inflammatory cytokines in lipopolysaccharide (LPS)-stimulated human epithelial-like SW480 and HT-29 cells. Our data showed that although piperine inhibited the proliferation of SW480 and HT-29 cells in a dose-dependent manner, it had low cytotoxicity on these cell lines with 50 % inhibiting concentration (IC50) values greater than 100 μM. As epithelial-like cells, SW480 and HT-29 cells secreted high levels of the chemokine CXCL8 upon LPS stimulation. Importantly, piperine dose-dependently suppressed LPS-induced secretion of CXCL8 and the expression of CXCL8 messenger RNA (mRNA). Although piperine failed to affect the critical inflammatory nuclear factor-κB pathway, it attenuated the c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) signaling. Consistent with previous reports, p38 signaling seemed to play a more pronounced role on the CXCL8 expression than JNK signaling since inhibition of p38, instead of JNK, greatly suppressed LPS-induced CXCL8 expression. Collectively, our results indicated that piperine could attenuate the inflammatory response in epithelial cells via downregulating the MAPK signaling and thus the expression of CXCL8, suggesting its potential application in anti-inflammation therapy.

The self-assembly of Ru2(CO3)43− paddle-wheel precursors and Mn2+ ions in aqueous solution yields various carbonate complexes. With appropriate selection of the synthetic conditions, we are able to intentionally tune the composition and structure of Mn–Ru2-carbonate assemblies to form infinite chain structural complexes, e.g., K[{Mn(H2O)4}2Ru2(CO3)4Br2]·H2O (1) and H[{Mn(H2O)4}2Ru2(CO3)4Br2]·6H2O (2). Complexes 1 and 2 are obtained at different temperatures (25 °C for 1 and 5 °C for 2, respectively), and their crystal structures consist of brick-wall stacked chains, in which neighboring Ru2(CO3)4Br25− units are linked by two disubstituted octahedral Mn(H2O)42+ in a cis manner, resulting in two isomeric (twisted and zigzag) negative double-chain α- and β-{[Mn(H2O)4]2Ru2(CO3)4Br2}nn−. The magnetic properties of complexes 1 and 2 were highly characterized. The alternating current (AC) susceptibility analysis of complex 1 reveals a two-step magnetism transition at T1 = 5.0 K and T2 = 2.6 K, respectively. Complex 2 exhibits metamagnetism behavior, with a transition field HC = ∼1.2 kOe at 2.0 K.

Quinone reductase 2 (NQO2) is a flavoprotein that catalyzes the metabolic reduction of quinines, but its biological mechanism in vascular smooth muscle cells (VSMCs) is unclear. The aim of this study was to evaluate the role of NQO2 on VSMCs proliferation and the neointimal formation in balloon injured rat carotid artery.Left common carotid arteries from Sprague-Dawley rats were injured by a balloon catheter, and the injured arteries were incubated with 50 μL solution of NQO2-siRNA-GFP lentiviral vectors, NC-siRNA-GFP lentiviral vectors or PBS for 1 h. The rats were euthanized for morphometric and immunohistochemical analysis, real-time PCR and western blot analysis at 2 weeks after balloon injury and gene transfer. The cultured rat VSMCs transduced with NQO2-siRNA-GFP or NC-siRNA-GFP lentiviral vectors were used for cell proliferation assay, real-time PCR and western blot analysis. In order to detect the vascular or intracellular ROS level, the lentiviral vectors without GFP were used to transfect the injured common carotid arteries and the cultured rat VSMCs.Lentiviral vectors bearing NQO2 siRNA could reduce NQO2 protein level and suppress NQO2 mRNA expression in balloon injured artery walls and cultured rat VSMCs. Downregulation of NQO2 significantly suppressed VSMCs proliferation and intimal formation. NQO2 siRNA treatment could reduce vascular or intracellular ROS level and decrease the phosphorylation of the ERK1/2 in balloon injured artery walls and cultured rat VSMCs.Our study suggests that downregulation of NQO2 significantly suppresses VSMCs proliferation and progression of neointimal formation after vascular injury.

This paper reports the crystal structure and magnetism properties of a novel mixed-valent diruthenium(II,III) complex, [C(NH2)3]4[Ru2(hedp)2(SCN)]·4H2O (1), where hedp represents 1-hydroxyethylidenediphosphonate. It shows a zigzag chain structure in which the paddlewheel diruthenium(II,III) dimers of Ru2(hedp)23 − linked by SCN− bridges. The chains are stacked along the [011] direction with strong intra- and interchain hydrogen bonds. Magnetic studies show that significant antiferromagnetic exchanges are mediated between the [Ru2(hedp)2]3 − (S = 3/2) units through thiocyanate ion bridges. Structural analysis proves that the Ru Ru bond weakening ability is H2O

Background: Only a few algorithms for predicting the site of origin of focal atrial tachycardia (AT) have been reported. We aimed to develop a new and more effective algorithm. Methods: Surface 12-lead electrocardiograms were collected during tachycardia and sinus rhythm in 61 patients who received successful radiofrequency ablation. P-wave polarities, durations, and amplitudes were analyzed. Predictive values of the most significant parameters were determined. An algorithm was then developed and prospectively evaluated in 30 new consecutive AT patients. Results: Thirty-six percent (22/61) of the foci were located at the ostium of coronary sinus (CS). Other common foci included pulmonary veins (PVs, n = 15), right atrial appendage (RAA, n = 7), parahisian area (n = 7), and crista terminalis (CT, n = 3). Positive P waves in inferior leads (II, III, and aVF) and a negative P wave in lead aVR indicated high atrial origins (high CT, superior PVs, and RAA, defined as Area A), with a sensitivity of 95% and a specificity of 90%. Negative P waves in inferior leads and a positive P wave in lead aVR suggested right low septal origins (CS ostium and inferior tricuspid annulus, defined as Area B), with good sensitivity and specificity (88% and 89%, respectively). This new P-wave diagnostic algorithm correctly identified the site of origin in 90% of AT cases. Conclusion: Combination of data from multiple leads and regrouping of sites of origin provides a better predictive value. (PACE 2011; 34:414–421)

To report the single-center clinical experience of catheter ablation of epicardial accessory pathway associated with coronary sinus musculature.The data of 721 cases of left sided accessory pathway ablation were retrospectively analyzed. Ablation in the coronary sinus was performed in 17 (2.4 %) cases [11 males, mean age (37 ± 11) years].Among the 17 cases, the accessory pathway was successfully ablated in middle cardiac vein and posterior lateral coronary sinus in 11 and 6 cases, respectively. Deverticulum of middle cardiac vein was seen in 2 cases. Mean time required to block the accessory pathway was (4.7 ± 2.7) s. An accessory pathway potential could be recorded at the target site in 10 out of 17 patients (59%). During a mean (21 ± 16) months follow up, only one patient experienced recurrence who was successfully cured by a second ablation session. No procedure related complication was reported.About 2.4% of left accessory pathway may have epicardial connection locating at middle cardiac vein or lateral part of the coronary sinus and require epicardial ablation. The epicardial ablation is safe and effective, warrants an excellent long-term results.

Recent studies suggest that cadherin-mediated adherens junctions may be impaired in diseases and pathologic processes related to ventricular arrhythmias, which are concomitant with decreased connexin 43 (Cx43). In this study, we evaluated the acute arrhythmogenic effects of adherens junction impairment in isolated rat hearts. A total of 56 hearts isolated from adult male rats were perfused with 0.2 mM AHAVD, a synthetic peptide that specifically inhibits N-cadherin (n = 18); 0.2 mM IPPINL, a nonsense peptidase that contains the highly conserved cadherin sequence (n = 18), and oxygenated Krebs–Henseleit buffer as the control (n = 20). Under programmed stimuli, ventricular tachyarrhythmias were induced more in the AHAVD-perfused hearts (9/18) than the IPPINL-perfused hearts (4/18) and those in the control (3/20) group (P

To explore the topographic distribution and long-term outcome of catheter ablation for focal atrial tachycardia (AT).The data of 207 patients who underwent electrophysiologic study for AT were retrospectively analyzed.A total of 200 AT were identified in 185 patients. The most common site for AT was ostium of the coronary sinus (23.8%), followed by crista terminalis (20.5%), perinodal area (20.0%), cava vena (17.8%), annulus (13.0%), and appendage (10.3%). Eighty percent AT originated from the right atrium, 17.8% originated from the left atrium. AT originated from the left atrium was more common in male than in female (25.0% vs. 13.3%, P = 0.042), while AT originated from the right atrium was more common in female than in male (69.4% vs. 86.7%, P = 0.004). Among the 185 patients, acute success ablation rate was 93.5% (n = 173). The acute success rate in the conventional mapping group was lower than that in the three-dimensional mapping group (79.3% vs. 96.5%, P0.01). During a median of 36 months follow up, the AT recurred in 20 patients (success ablation rate 88.4%). Success ablation rate was similar between the conventional mapping group and the three-dimensional mapping group (P0.05).Focal AT commonly originates from ostium of coronary sinus, crystal terminalis, perinodal area, and cava veins. There is a gender related difference in the distribution of focal AT. The radiofrequency catheter ablation yields a satisfying success rate and very low complication rate and could be the first line choice for treating ATs in experienced electrophysiological center.

To summarize the clinical characteristics of congenital ventricular aneurysm and diverticula in inland China.To identify the literature of congenital aneurysm and diverticula from Wanfang, China National Knowledge Infrastructure (CNKI) and PubMed databases, and to analyze the clinical characteristics of congenital aneurysm and diverticula from January of 2001 to December of 2009.A total of 116 patients [78 men, 1 - 80 (33.5 ± 21.3) years old] with congenital aneurysm or diverticula were included in 109 articles. Twenty-five patients (13 men) were congenital ventricular aneurysm, including a family of 4 patients. Ninety-one patients (65 men) were congenital ventricular diverticula. One hundred patients were detected by echocardiography during medical examination, 34 patients combined with other cardiac anomalies, 4 of which with extracardiac structures. There were 8 patients with ventricular arrhythmia, 8 patients with thrombosis, 2 patients died of cardiac rupture, 4 patients died of sudden death, surgical operation was performed in 46 patients and 3 patients received ablation procedure. All patient did not receive implantable cardioverter defibrillator (ICD) implantation.Congenital ventricular aneurysm or diverticulum is a rare cardiac malformation. Most congenital left ventricular aneurysms and diverticula are asymptomatic and detected by echocardiography. Congenital ventricular aneurysm or diverticulum may cause ventricular tachycardia, ventricular wall rupture, systemic embolization or sudden death, which had to be treated individually.

To explore the effectiveness of the metoprolol dosage adjustment on reducing the incidence of electrical-storm (ES) in patients with Implantable Cardioverter Defibrillators (ICDs).Data from patients with ICD implantation between Jan, 2003 and Jun, 2006 in our hospital were retrospectively analyzed. ES was defined as either ≥ 3 times of ventricular tachyarrhythmias (VTAs) resulting in ICD therapy or VTAs lasting more than 30 s detected by ICD without any therapy within 24 hours.During a follow-up period of (27.5 ± 21.2) months, ES was recorded in 39 cases [34 males, average age (52.0 ± 13.1) years] out of 119 patients (32.8%) and 9 patients died after ES. During the period of storm attack, ES was successfully controlled in 25/30 patients by various interventions, including predisposing factors corrected in 5 cases, ICD reprogramming and antiarrhythmic drugs therapy optimized in 16 cases (one received intravenous injection of metoprolol), and VTAs eliminated by catheter ablation in 4 cases. ES was spontaneously resolved in the remaining 5 cases. In the chronic phase, 2 patients with Brugada syndrome were treated with Quinidine mono-therapy while the dosage of metoprolol was adjusted in the remaining 23 patients and the dosage of metoprolol was increased gradually from (26.8 ± 13.9) mg/d to (88.9 ± 53.5) mg/d without any adverse effects (9 patients received also oral amiodarone 200 mg/d). Post dosage adjustment, the total VTA episodes [(1.9 ± 1.7) times/month vs. (0.8 ± 0.6) times/month, P = 0.004], incidence of antitachycardia pacing therapies [(4.2 ± 3.8) runs/month vs. (2.3 ± 2.0) runs/month, P = 0.003], as well as electrical cardioversion or defibrillation [(1.1 ± 0.9) times/month vs. (0.4 ± 0.2) times/month, P = 0.001] were significantly decreased. ES was not controlled until a extremely high dosage [225 - 300 (255.3 ± 41.7) mg/d] of metoprolol was reached in the remaining 5 patients.Metoprolol use is essential and its dosage should be individualized in the majority of ICD recipients with ES. In approximately 1/6 patients, the dosage of metoprolol should be higher than 200 mg/d.

High degree atrioventricular block (HDAVB) is a serious complication of transcatheter closure of a perimembranous ventricular septal defect (PMVSD). We report one patient who developed transient HDAVB seven days after transcathter closure of PMVSD and had recurrent HDAVB 42 months after the procedure.

Only a few algorithms for predicting the site of origin of focal atrial tachycardia (AT) have been reported. We aimed to develop a new and more effective algorithm.Surface 12-lead electrocardiograms were collected during tachycardia and sinus rhythm in 61 patients who received successful radiofrequency ablation. P-wave polarities, durations, and amplitudes were analyzed. Predictive values of the most significant parameters were determined. An algorithm was then developed and prospectively evaluated in 30 new consecutive AT patients.Thirty-six percent (22/61) of the foci were located at the ostium of coronary sinus (CS). Other common foci included pulmonary veins (PVs, n = 15), right atrial appendage (RAA, n = 7), parahisian area (n = 7), and crista terminalis (CT, n = 3). Positive P waves in inferior leads (II, III, and aVF) and a negative P wave in lead aVR indicated high atrial origins (high CT, superior PVs, and RAA, defined as Area A), with a sensitivity of 95% and a specificity of 90%. Negative P waves in inferior leads and a positive P wave in lead aVR suggested right low septal origins (CS ostium and inferior tricuspid annulus, defined as Area B), with good sensitivity and specificity (88% and 89%, respectively). This new P-wave diagnostic algorithm correctly identified the site of origin in 90% of AT cases.Combination of data from multiple leads and regrouping of sites of origin provides a better predictive value.

Right Free Wall Accessory Pathway Ablation. Introduction: The aim of this study was to delineate the electroanatomic substrates of right-sided free wall (RFW) accessory pathways (APs) that were refractory to conventional catheter ablation utilizing 3-dimensional (3-D) mapping. Methods and Results: Eleven patients with RFW APs that failed initial conventional catheter ablation(s) by a mean of 1.9 ± 0.5 attempts were enrolled in the study. Electroanatomic mapping of the right atrium was performed during orthodromic reciprocating tachycardia in 3 patients and right ventricular pacing in 8 patients. The earliest atrial activation site, which represented the atrial insertion of the AP, was separated from the tricuspid annulus by an average of 14.3 ± 3.9 mm, and the local activation time was 27.8 ± 17.0 ms earlier than that of the corresponding annular point. One patient exhibited an AP with wide branching on the atrial side. RF ablation with an irrigated catheter successfully interrupted AP conduction in all patients without complications. Conclusions: RFW APs resistant to conventional catheter ablation might be due to unique anatomic AP features such as more epicardial course at the annulus level with atrial insertion distant from the tricuspid annulus. Electroanatomic mapping is helpful to accurately localize the atrial insertion sites of these APs and facilitates catheter ablation. (J Cardiovasc Electrophysiol, Vol. 21, pp. 1317-1324, December 2010)

To investigate the prevalence of Epsilon wave in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC).The epsilon wave was detected in 32 patients [24 men, mean age (42.3 +/- 13.3) years] with ARVC using three different electrocardiography (ECG) recording methods: standard twelve leads ECG (S-ECG), right precordial leads ECG (R-ECG) and Fontaine bipolar precordial leads ECG (F-ECG). The Epsilon wave was defined as wiggler, small spike wave and smooth potential between the end of the QRS complex and the beginning of the ST segment.Epsilon wave was detected in 37.5%, 37.5% and 50.0% patients with ARVC by S-ECG, R-ECG and F-ECG respectively. The detection rates derived from the three recording methods were similar (P0.05). The Epsilon wave was only detectable by S-ECG in one case, by R-ECG in three cases, and by F-ECG in five cases. The detection rate of Epsilon wave was 50.0% by combined use of S-ECG and R-ECG (SR-ECG), 56.3% by combined use of S-ECG and F-ECG (SF-ECG), and 65.6% by combined use of the three recording methods (SRF-ECG). The detection rate was significantly higher by SF-ECG (56.3%) and SRF-ECG (65.6%) than by S-ECG alone (37.5%, all P0.05). Most Epsilon waves detected by the S-ECG, R-ECG and F-ECG were small spiked waves.Combined use of S-ECG, F-ECG and R-ECG could increase the detection rate of Epsilon wave in patients with ARVC.