Search

Background Previous studies have demonstrated that WenXin KeLi (WXKL), a traditional Chinese medicine, can exert antiarrhythmic properties through complex multichannel inhibition, but its pharmacologic effect remains to be elucidated, especially in the cardiac conductive system. Objective To explore the antiarrhythmic property of WXKL in cardiac Purkinje cells (PCs). Methods PCs were isolated from rabbit hearts and action potentials (APs) and ion currents were recorded by whole-cell patch clamp technique. Anemonia toxin II (ATX-II) and isoproterenol (ISO) were used to induce early or delayed afterdepolarizations (EADs, DADs) or triggered activities (TAs). Results WXKL (1 g/L and 5 g/L) significantly abbreviated the action potential duration (APD) of PCs in a dose- and rate-dependent manner. Treatment of PCs with ATX-II (2 nM) prolonged APD and induced EADs, which were significantly suppressed by WXKL. WXKL (1, 5 g/L) also inhibited ISO-induced EADs, DADs, and TAs. To reveal the ionic mechanisms, we studied the effects of WXKL on late sodium current (I NaL ), peak sodium current (I NaP ), and L-type calcium currents (I CaL ) in PCs. WXKL-attenuated ATX-II (5 nM) induced I NaL augmentation and blocked I NaL with an IC 50 of 4.3 ± 0.5 g/L, which is 3- to 4-fold more selective than that of I NaP (13.3 ± 0.9 g/L) and I CaL (17.6 ± 1.4 g/L). Moreover, WXKL exerted significantly less use-dependent block of I NaP than that of flecainide, indicating its lower proarrhythmic effect. Conclusions WXKL exhibits antiarrhythmic properties in cardiac PCs via selective inhibition of I NaL .

To investigate the cardioprotective effect of salidroside to rat heart subjected to 8-hour hypothermic storage and 2-hour normothermic reperfusion. Isolated rat hearts were perfused with Langendorff model; after 30 minutes of baseline, the hearts were arrested and stored by St. Thomas solution (STS) without (STS group) or with different concentration salidroside at 4 °C for 8 hours, then reperfused for 2 hours. Compared with STS group, both middle and high dosage in STS greatly improved the recovery of left ventricular developed pressure (LVDP), maximum LVDP increase and decrease rate (±dp/dt), coronary flow rate (CF). Our study demonstrated that the salidroside was beneficial to improving cardiac functional recovery.

Solid oxide fuel cell (SOFC) is a high efficiency clean device that directly converts chemical energy of the fuel gas into electric energy. The long-term degradation and stability are the main problems at high temperature, so how to reduce the working temperature becomes a hotspot of research. It is an important way to reduce the thickness of electrolyte. Therefore, how to produce dense and thin electrolyte films economically becomes particularly important. It has been reported that a uniform and dense coating is hopefully prepared by using very low pressure plasma spraying (VLPPS) technology. Due to low operating pressure (~100 Pa), the plasma plume length elongates and its diameter enlarges. Under this condition, the particles can been heated for more time, and it is helpful to form dense coatings. The current study focuses on this technology for application in porous metal supported solid oxide fuel cell (MS-SOFC), especially for preparation in electrolyte. Using SEM, it was found that the densification of the electrolyte was very well, and this could be confirmed by the open-circuit voltage (OCV) of the cell. In the temperature range of 550~750 ℃, the OCV of the cell fairly stabilized between 1.05 V and 1.1 V. The cell was also analyzed by using electrochemical impedance spectroscopy (EIS). The maximum power density of the cell could be up to more than 1200 mW/cm2 at 750 ℃. The long-term stability of the cell was also preliminarily explored, and the result has shown that it is a very promising method for application in MS-SOFC.

Background: Hydrogen peroxide (H2O2)-induced oxidative stress has been demonstrated to induce afterdepolarizations and triggered activities in isolated myocytes, but the underlying mechanisms remain not fully understood. We aimed to explore whether protein kinase C (PKC) activation plays an important role in oxidative stress-induced afterdepolarizations. Methods: Action potentials and ion currents of isolated rabbit cardiomyocytes were recorded using the patch clamp technique. H2O2 (1 mM) was perfused to induce oxidative stress and the specific classical PKC inhibitor, Gö 6983 (1 μM), was applied to test the involvement of PKC. Results: H2O2 perfusion prolonged the action potential duration and induced afterdepolarizations. Pretreatment with Gö 6983 prevented the emergence of H2O2-induced afterdepolarizations. Additional application of Gö 6983 with H2O2 effectively suppressed H2O2-induced afterdepolarizations. H2O2 increased the late sodium current (INa,L) (n = 7, p < 0.01) and the L-type calcium current (ICa,L) (n = 5, p < 0.01), which were significantly reversed by Gö 6983 (p < 0.01). H2O2 also increased the transient outward potassium current (Ito) (n = 6, p < 0.05). However, Gö 6983 showed little effect on H2O2-induced enhancement of Ito. Conclusions: H2O2 induced afterdepolarizations via the activation of PKC and the enhancement of ICa,L and INa,L. These results provide evidence of a link between oxidative stress, PKC activation and afterdepolarizations.

Mitogen-activated protein kinase (MAPK) cascades are important players in the overall representation of cellular signal transduction pathways, and the deregulation of MAPKs is involved in a variety of diseases. The activation of MAPK signals occurs through phosphorylation by MAPK kinases at conserved threonine and tyrosine (Thr-Xaa-Tyr) residues. The mitogen-activated protein kinase phosphatases (MKPs) are a major part of the dual-specificity family of phosphatases and specifically inactivate MAPKs by dephosphorylating both phosphotyrosine and phosphoserine/phosphothreonine residues within the one substrate. MAPKs binding to MKPs can enhance MKP stability and activity, providing an important negative-feedback control mechanism that limits the MAPK cascades. In recent years, accumulating and compelling evidence from studies mainly employing cultured cells and mouse models has suggested that the archetypal MKP family member, MKP-1, plays a pivotal role in cardiovascular disease as a major negative modulator of MAPK signaling pathways. In the present review, we summarize the current knowledge on the pathological properties and the regulation of MKP-1 in cardiovascular disease, which may provide valuable therapeutic options.

The aim of the present study was to observe the myocardial expression of members of the histone deacetylase (HDAC) family (HDAC2, HDAC5 and HDAC9) in rats with or without myocardial hypertrophy (MH) in the presence and absence of the angiotensin II receptor blocker valsartan. Adult male Wistar rats were randomly divided into three groups (n=6/group): Sham-operated control rats, treated with distilled water (1 ml/day) through gavage; rats with MH (established through aortic constriction), treated with distilled water (1 ml/day) through gavage; and MH + valsartan rats, treated with 20 mg/kg/day valsartan through gavage. Treatments commenced one day after surgery and continued for eight weeks. Body weight (BW), heart weight (HW) and plasma atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) levels were determined, and the myocardial expression of HDAC2, HDAC5 and HDAC9 was analyzed through a reverse transcription semi-quantitative polymerase chain reaction. The BWs of the rats in the three groups were similar at baseline; however, after eight weeks the BW of the rats in the MH + valsartan group was significantly reduced compared with that of the MH rats. Furthermore, the HW/BW ratio and plasma ANP and BNP levels were increased, the myocardial HDAC2 expression was significantly upregulated and the HDAC5 and HDAC9 expression was significantly downregulated in the MH rats compared with those in the control rats; however, these changes were significantly attenuated by valsartan. Modulation of myocardial HDAC5, HDAC9 and HDAC2 expression may therefore be one of the anti-hypertrophic mechanisms of valsartan in this rat MH model.

Pulmonary vein antrum isolation (PVAI) of pre-excited atrial fibrillation (AF) is controversial. This study aimed to observe the therapeutic effects of PVAI on pre-excited AF.Twenty-nine patients with pre-excited AF were prospectively divided into a PVAI group (group I, 19 cases) and a control group (group II, 10 cases). To each case in group I, PVAI was performed, and then electroanatomical mapping of accessory pathways (AP) and ablation were constructed on a three-dimensional (3D) map of the valve annulus. Only AP ablation was performed in each case of group II.Of the 29 cases, three were found to have dual APs, two had intermittent APs, and the remaining 24 had single APs. All APs were successfully ablated after the procedure. There were no significant statistical differences in the AP procedure duration ((77.4 ± 21.3) minutes vs. (85.3 ± 13.1) minutes), the AP ablation time ((204 ± 34) seconds vs. (223 ± 62) seconds) and the AP X-ray exposure time ((18.6 ± 4.4) minutes vs. (19.1 ± 4.5) minutes) respectively between groups I and II. As compared with the control group (5 of 10 cases, 50%), the PVAI group had a significantly lower AF recurrence rate (2 of 19 cases, 11%; P0.05) during follow-up of (20.5 ± 10.0) months. All seven patients who recurred were successfully abolished by a second ablation.In patients with pre-excited AF, PVAI is an effective therapeutic approach with a low AF recurrence rate. 3D electroanatomical maps of AP contributed to the high success rate of ablation without significantly prolonging of operational duration and X-ray exposure time.

To investigate whether resveratrol suppressed oxidative stress-induced arrhythmogenic activity and Ca(2+) overload in ventricular myocytes and to explore the underlying mechanisms.Hydrogen peroxide (H2O2, 200 μmol/L)) was used to induce oxidative stress in rabbit ventricular myocytes. Cell shortening and calcium transients were simultaneously recorded to detect arrhythmogenic activity and to measure intracellular Ca(2+) ([Ca(2+)]i). Ca(2+)/calmodulin-dependent protein kinases II (CaMKII) activity was measured using a CaMKII kit or Western blotting analysis. Voltage-activated Na(+) and Ca(2+) currents were examined using whole-cell recording in myocytes.H2O2 markedly prolonged Ca(2+) transient duration (CaTD), and induced early afterdepolarization (EAD)-like and delayed afterdepolarization (DAD)-like arrhythmogenic activity in myocytes paced at 0.16 Hz or 0.5 Hz. Application of resveratrol (30 or 50 μmol/L) dose-dependently suppressed H2O2-induced EAD-like arrhythmogenic activity and attenuated CaTD prolongation. Co-treatment with resveratrol (50 μmol/L) effectively prevented both EAD-like and DAD-like arrhythmogenic activity induced by H2O2. In addition, resveratrol markedly blunted H2O2-induced diastolic [Ca(2+)]i accumulation and prevented the myocytes from developing hypercontracture. In whole-cell recording studies, H2O2 significantly enhanced the late Na(+) current (I(Na,L)) and L-type Ca(2+) current (I(Ca,L)) in myocytes, which were dramatically suppressed or prevented by resveratrol. Furthermore, H2O2-induced ROS production and CaMKII activation were significantly prevented by resveratrol.Resveratrol protects ventricular myocytes against oxidative stress-induced arrhythmogenic activity and Ca(2+) overload through inhibition of I(Na,L)/I(Ca,L), reduction of ROS generation, and prevention of CaMKII activation.

Nitric oxide (NO) exerts various pathophysiological effects on the cardiovascular system; inhibition of platelet aggregation or leukocyte adhesion on endothelium and vasorelaxation including lethal hypotension in endotoxic shock. In spite of these significant roles of NO, its direct action on individual cardiovascular cells remains unclarified. Therefore, we have investigated the function of NO on cells which constitute vascular wall and heart, and have found this new evidence. 1) ATP increased intracellular ([Ca2+]i) in vascular endothelial cells (ECs) and decreased [Ca2+]i of adjacently cocultured vascular smooth muscle cells (VSMCs), as detected by 2-D fura-2 image analysis. 2) The [Ca2+]i reduction in cocultured VSMCs with ECs by ATP was attenuated by pretreatment of several types of NO inhibitor, whereas the NO inhibitor potentiated the [Ca2+]i elevation in ECs, suggesting that NO affects VSMCs in a paracrine manner while ECs in an autocrine fashion. 3) Physiological concentration of lysophosphatidylcholine, which is an atherogenic constituent of oxidized LDL, but not native phosphatidylcholine, acted on ECs and VSMCs like a NO inhibitor, indicating that this material attenuates NO effect and disturbs vessel relaxation in the short term. 4) Highly efficient transfection of the ecNOS gene in rat heart showed a toxic effect on individual cardiomyocytes in vivo. In conclusion, NO may exert both beneficial and harmful effects on the cardiovascular system.

The role of genetic abnormality of δ-sarcoglycan (δ-SG) gene in dilated (DCM) and hypertrophied (HCM) cardiomyopathy patients is still unfolding. In this study we first defined the promoter region and then searched for polymorphisms/mutations among the promoter, 5'-untranslated region, and the encoding exons in δ-SG gene in 104 Chinese patients with DCM, 145 with HCM, and 790 normal controls. Two novel polymorphisms were found, an 11 base-pair (bp) deletion (c.-100~-110; -) in the promoter region and a missense polymorphism of A848G resulting in p.Q283R in the highly conserved C-terminus. The prevalence of homozygous genotype -/- of c.-100~-110 was slightly higher in DCM (14.42%) and HCM patients (14.48%), as compared with normal controls (11.01%). The prevalence of genotype of 848A/G was significantly higher in DCM (6.73%; OR = 9.43; p = 0.0002), but not in HCM patients (1.38%; OR = 1.37; p = 0.62), as compared with controls (0.76%). Haplotype -_G consisting c.-100~-110 and A848G was associated with increased risk of DCM (OR = 17.27; 95%CI = 3.19–93.56; p = 0.001) but not associated with HCM (OR = 1.90; 95%CI = 0.38–9.55; p = 0.44). Co-occurrence of the genotypes -/- of c.-100~-110 and 848A/G was found in 5 patients with DCM (4.81%; OR = 39.85; p = 0.0001), none of HCM patients, and only 1 of the controls (0.13%). Both polymorphisms were also found in the Japanese population, but not in the Africans and Caucasians. C.-100~-110 resulted in a decrease of δ-SG promoter activity to 64±3% of the control level (p

Aims Myocardial infarction (MI) induces neural remodelling of the left stellate ganglion (LSG), which may contribute to ischaemia-induced arrhythmias. The neural chemorepellent Semaphorin 3a (Sema3a) has been identified as a negative regulator of sympathetic innervation in the LSG and heart. We previously reported that overexpression of Sema3a in the border zone could reduce the arrhythmogenic effects of cardiac sympathetic hyperinnervation post-MI. This study investigated whether Sema3a overexpression within the LSG confers an antiarrhythmic effect after MI through decreasing extra- and intra-cardiac neural remodelling. Methods and results Sprague-Dawley rats were subjected to MI, and randomly allocated to intra-LSG microinjection of either phosphate-buffered saline (PBS), adenovirus encoding green fluorescent protein (AdGFP), or adenovirus encoding Sema3a (AdSema3a). Sham-operated rats served as controls. Two weeks after infarction, MI-induced nerve sprouting and sympathetic hyperinnervation in the LSG and myocardium were significantly attenuated by intra-LSG injection with AdSema3a, as assessed by immunohistochemistry and western blot analysis of growth-associated protein 43 and tyrosine hydroxylase. This was also confirmed by sympathetic nerve function changes assessed by cardiac norepinephrine content. Additionally, intra-LSG injection with AdSema3a alleviated MI-induced accumulation of dephosphorylated connexin 43 in the infarct border zone. Furthermore, Sema3a overexpression in the LSG reduced the incidence of inducible ventricular tachyarrhythmia by programmed electrical stimulation post-MI, and arrhythmia scores were significantly lower in the AdSema3a group than in the PBS and AdGFP groups. Conclusion Semaphorin 3a overexpression in the LSG ameliorates the inducibility of ventricular arrhythmias after MI, mainly through attenuation of neural remodelling within the cardiac-neuraxis.

As a kind of promising and potential data assimilation technique to which various countries’ meteorologists had attached great importance, the variational data assimilation had so far become the main development direction in meteorological data assimilation. So this paper is limited to illustrate the main idea of the variational adjoint method by constructing the variational adjoint system which here has a nonlinear variable-coefficient convection-diffusion equation at its core, and show how this method can be achieved from the mathematical point of view. As a result, the desired gradient formulas required for the descent of objective function are derived.

In view of semiconductor probe system's production scheduling problem, with the thought of object-oriented, a probe behavior model is set up in terms of the figuration of UML which is a model tool. It uses the SimTalk brought by EM-plant to transform behavior model directly into simulation model. By analyzing the experimental result of simulation model, the influence of the wafer releasing speed and machine dispatching upon system performance indicators such as system capability, production cycle, utilization of machines and quantity of work in process are got. It supplies the decision maker with evidence.

AIM: To study the effects of extract from Ginkgo biloba (EGb) containing 22% flavonoid and 5% terpenoid on chronic liver injury and liver fibrosis of rats induced by carbon tetrachloride (CCl4). METHODS: All rats were randomly divided into control group, CCl4-treated group, colchicine-treated group and EGb-protected group. Chronic liver injury was induced in experimental groups by subcutaneous injection of CCl4 and fed with chows premixed with 79.5% corn powder, 20% lard and 0.5% cholesterol (v/v). EGb-protected group was treated with EGb (0.5 g/kg body weight per day) for 7 wk. At the end of wk 8, all the rats were killed. Liver function, liver fibrosis, oxidative stress and expression of transforming growth factor β1 (TGF-β1), a-smooth muscle actin (α-SMA) and type I collagens in liver were determined. In addition, pathology changes of liver tissue were observed under light microscope. RESULTS: The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and albumin (Alb) in EGb-protected group were notably improved as compared with the CCL4-treated group (P < 0.01). The contents of serum hyaluronic acid (HA), type III procollagen (PCIII), type IV collagen (CIV) and the expression of hepatic tissue TGF-β1, α-SMA and type I collagen in EGb-protected group were significantly lower than those in CCL4-treated groups (P < 0.05, P < 0.01). The degrees of liver fibrosis in EGb-protected groups were lower than those in CCL4-treated groups (6.58 ± 1.25 vs 9.52 ± 2.06, P < 0.05). Compared to the CCL4-treated group, the levels of plasma glutathoine peroxidase (Se-GSH-Px), superoxide dismutase (SOD) and malondialdehyde (MDA) were strikingly improved also in EGb-protected group (P < 0.05, P < 0.01). CONCLUSION: EGb resists oxidative stress and thereby reduces chronic liver injury and liver fibrosis in rats with liver injury induced by CCl4.