Ivabradine inhibits the production of proinflammatory cytokines and inducible nitric oxide synthase in acute coxsackievirus B3-induced myocarditis.

The role of ß-adrenergic stimulation on viral myocarditis has been investigated in animal models. The beneficial action of the ß-blocker carvedilol in murine viral myocarditis can be explained partly by the resulting heart rate reduction and the inhibition of proinflammatory cytokine production. The modulation of myocardial necrosis and contractile dysfunction by proinflammatory cytokines may be partially mediated by the production of nitric oxide (NO). The selective I(f) current inhibitor ivabradine reduces the heart rate without affecting cardiac contractility and has been shown to be cardioprotective in failing hearts. However, little is known about the effects of ivabradine in viral myocarditis, and in particular, its effects on inducible NO synthase (iNOS) have not been investigated. This study was therefore designed to examine the effects of ivabradine in murine viral myocarditis. In a coxsackievirus B3 murine myocarditis model, the effects of ivabradine and carvedilol on the myocardial histopathological changes and fibrosis, NO production, iNOS protein and cytokine levels were studied. Both ivabradine and carvedilol similarlyattenuated myocardial lesions and fibrosis, inhibited NO synthesis by iNOS, and decreased the production of TNF-α and IL-6. These results show that ivabradine has a therapeutic benefit in murine CVB3-induced myocarditis. The beneficial effects of ivabradine in viral myocarditis are partially mediated by the inhibition of both the production of proinflammatory cytokines and the synthesis of NO by iNOS.

Effects of carvedilol treatment on cardiac cAMP response element binding protein expression and phosphorylation in acute coxsackievirus B3-induced myocarditis.

BACKGROUND: The role of ß-adrenergic stimulation on viral myocarditis has been investigated in animal models of viral myocarditis. Excess stimulation of ß-adrenergic receptors by catecholamines causes phosphorylation/activation of cAMP response element binding protein (CREB) by the cAMP signaling pathway. CREB as an important regulator of gene expression mediates the cardiovascular remodeling process and promotes anti-inflammatory immune responses. However, the CREB expression and phosphorylation have not been studied, and the effects of carvedilol (a nonselective ß-adrenoceptor antagonist) on the CREB has not been investigated in the setting of acute viral myocarditis. METHODS: This study was therefore designed to examine the effects of carvedilol on the transcriptional factor CREB in a murine model of acute viral myocarditis. In a coxsackievirus B3 murine myocarditis model (Balb/c), effects of carvedilol on plasma noradrenaline, heart rate and blood pressure, myocardial histopathological changes and fibrosis, cardiomyocyte apoptosis, cardiac CREB and phosphorylated CREB, cytokine levels, and viral RNA were studied. RESULTS: The expression and phosphorylation of CREB were decreased with concomitant increase of IL-6 and TNF-α in murine coxsackievirus-induced acute viral myocarditis. The levels of IL-6 and TNF-α were correlated with the expression of CREB or phosphorylated CREB. Carvedilol increased the cardiac CREB expression and phosphorylation and decreased the plasma catecholamine levels and the production of IL-6 and TNF-α with amelioration of acute viral myocarditis. CONCLUSION: These results show that CREB may be involved in the pathophysiology of viral myocarditis and carvedilol exerts some of its beneficial effects by increasing the CREB expression and phosphorylation.

Idiopathic premature ventricular contractions and ventricular tachycardias originating from the vicinity of tricuspid annulus: results of radiofrequency catheter ablation in thirty-five patients.

BACKGROUND: In recent years, catheter ablation has increasingly been used for ablation of idiopathic premature ventricular complexes (PVCs) or ventricular tachycardias (IVTs). However, the mapping and catheter ablation of the arrhythmias originating from the vicinity of tricuspid annulus (TA) may not be fully understood. This study aimed to investigate electrophysiologic characteristics and effects of radiofrequency catheter ablation (RFCA) for patients with symptomatic PVCs and IVTs originating from the vicinity of TA. METHODS: Characteristics of body surface electrocardiogram (ECG) and electrophysiologic recordings were analyzed in 35 patients with symptomatic PVCs/ IVTs originating from the vicinity of TA. RFCA was performed using pace mapping and activation mapping. RESULTS: Among the 35 patients with PVCs/IVTs arising from the vicinity of TA, complete elimination of PVCs/IVTs could be achieved by RFCA in 32 patients (success rate 91.43%) during a median follow-up period of 21 months. PVCs/IVTs originating from the vicinity of TA had distinctive ECG characteristics that were useful for identifying the precise origin. An rS pattern was recorded in lead V1 in 93.1% of patients with PVCs/IVTs from the free wall of TA, vs 16.7% of patients with PVCs/IVTs from the septal TA, whereas a QS pattern in lead V1 occurred in 83.3% of patients with PVCs/IVTs from the septal TA vs 6.9% of patients with PVCs from the free wall of the TA. The precordial R wave transition occurred by lead V3 or earlier in all patients with PVCs/IVTs originating from the septal portion of the TA, as compared to transition beyond V3 in all patients with PVCs/IVTs from the free wall of the TA. CONCLUSIONS: RFCA is an effective curative therapy for symptomatic PVCs/IVTs originating from the vicinity of TA. There are specific characteristics in ECG and the ablation site could be located by ECG analysis.

Synthesis of Superionic Conductive Li1+x+yAlxSiyTi2-xP3-yO12 Solid Electrolytes.

Commercial lithium-ion batteries using liquid electrolytes are still a safety hazard due to their poor chemical stability and other severe problems, such as electrolyte leakage and low thermal stability. To mitigate these critical issues, solid electrolytes are introduced. However, solid electrolytes have low ionic conductivity and inferior power density. This study reports the optimization of the synthesis of sodium superionic conductor-type Li1.5Al0.3Si0.2Ti1.7P2.8O12 (LASTP) solid electrolyte. The as-prepared powder was calcined at 650 °C, 700 °C, 750 °C, and 800 °C to optimize the synthesis conditions and yield high-quality LASTP powders. Later, LASTP was sintered at 950 °C, 1000 °C, 1050 °C, and 1100 °C to study the dependence of the relative density and ionic conductivity on the sintering temperature. Morphological changes were analyzed using field-emission scanning electron microscopy (FE-SEM), and structural changes were characterized using X-ray diffraction (XRD). Further, the ionic conductivity was measured using electrochemical impedance spectroscopy (EIS). Sintering at 1050 °C resulted in a high relative density and the highest ionic conductivity (9.455 × 10-4 S cm-1). These findings corroborate with the activation energies that are calculated using the Arrhenius plot. Therefore, the as-synthesized superionic LASTP solid electrolytes can be used to design high-performance and safe all-solid-state batteries.

Premature ventricular contractions originating from the left ventricular septum: results of radiofrequency catheter ablation in twenty patients.

BACKGROUND: RFCA has been established as an effective and curative therapy for severely symptomatic PVC from the outflow tract in structurally normal hearts. However, it is unknown whether PVCs originating from the left ventricular septum, are effectively eliminated by RFCA. This study aimed to investigate electrophysiologic characteristics and effects of radiofrequency catheter ablation (RFCA) for patients with symptomatic premature ventricular contraction (PVC) originating from the left ventricular septum without including fascicular PVCs. METHODS: Characteristics of body surface electrocardiogram (ECG) and electrophysiologic recordings endocardiogram in a successful RFCA target were analyzed in 20 patients with symptomatic PVCs originating from the left ventricular septum. RFCA was performed using pace mapping and activation mapping. RESULTS: The QRS morphology of PVCs originating from the left ventricular septum is similar to that seen in fascicular tachycardia. Most of the PVCs originated from the left septum appears in the form of ventricular parasystole. The incidence of ventricular parasystole was 70%. Sustained ventricular tachycardia was not inducible by electrical stimulation and isoproterenol infusion in all 20 patients, ablation at the site recording the earliest Purkinje potential was not effective in all 20 patients, and Purkinje potentials were not identified at successful sites during point mapping. Sixteen patients were successful with RFCA using pace mapping and activation mapping, 3 failed, and 1 recurrent. CONCLUSION: Although the ECG characteristics of the PVCs arising from the left ventricular septum are similar to that seen in fascicular tachycardia, the electrophysiologic characteristics are different between the two types of PVCs. The distinguishing characteristic of the PVCs is that Purkinje potentials were not present at the site of successful ablation, suggesting a myocardial as opposed to fascicular substrate. RFCA is an effective curative therapy for symptomatic PVCs originating from the left ventricular septum (not from the left anterior and posterior fascicle).

Duration of antibody responses after severe acute respiratory syndrome.

Among 176 patients who had had severe acute respiratory syndrome (SARS), SARS-specific antibodies were maintained for an average of 2 years, and significant reduction of immunoglobulin G-positive percentage and titers occurred in the third year. Thus, SARS patients might be susceptible to reinfection >or=3 years after initial exposure.

Comparison of effects of ivabradine versus carvedilol in murine model with the Coxsackievirus B3-induced viral myocarditis.

BACKGROUND: Elevated heart rate is associated with increased cardiovascular morbidity. The selective I(f) current inhibitor ivabradine reduces heart rate without affecting cardiac contractility, and has been shown to be cardioprotective in the failing heart. Ivabradine also exerts some of its beneficial effects by decreasing cardiac proinflammatory cytokines and inhibiting peroxidants and collagen accumulation in atherosclerosis or congestive heart failure. However, the effects of ivabradine in the setting of acute viral myocarditis and on the cytokines, oxidative stress and cardiomyocyte apoptosis have not been investigated. METHODOLOGY/PRINCIPAL FINDINGS: The study was designed to compare the effects of ivabradine and carvedilol in acute viral myocarditis. In a coxsackievirus B3 murine myocarditis model (Balb/c), effects of ivabradine and carvedilol (a nonselective ß-adrenoceptor antagonist) on myocardial histopathological changes, cardiac function, plasma noradrenaline, cytokine levels, cardiomyocyte apoptosis, malondialdehyde and superoxide dismutase contents were studied. Both ivabradine and carvedilol similarly and significantly reduced heart rate, attenuated myocardial lesions and improved the impairment of left ventricular function. In addition, ivabradine treatment as well as carvedilol treatment showed significant effects on altered myocardial cytokines with a decrease in the amount of plasma noradrenaline. The increased myocardial MCP-1, IL-6, and TNF-α. in the infected mice was significantly attenuated in the ivabradine treatment group. Only carvedilol had significant anti-oxidative and anti-apoptoic effects in coxsackievirus B3-infected mice. CONCLUSIONS/SIGNIFICANCE: These results show that the protective effects of heart rate reduction with ivabradine and carvedilol observed in the acute phase of coxsackievirus B3 murine myocarditis may be due not only to the heart rate reduction itself but also to the downregulation of inflammatory cytokines.

[Surveillance program set for influenza A virus (H1N1) in children in Taiyuan, China, 2005-2006].

OBJECTIVE: To study the epidemic situation and dominant strain of influenza in children with acute respiratory infection (ARI) during Flu season from Oct. 2005 to Mar. 2006 in Taiyuan. METHODS: Madin-darby canine kidney (MDCK) cell culture and hemagglutination inhibition (HI) assay were used to isolate and identify type A influenza viruses (H1N1 and H3N2) and B influenza viruses from clinical samples collected from outpatients who visited the Department of Pediatric because of ARI from Oct. 2005 to Mar. 2006. Oct. 2005 and Mar. 2006, we collected 415 blood samples from children and adults to detect the influenza virus antibody titers by HI test to exclude respiratory diseases. RESULTS: 7 strains of H1N1 were isolated from 87 clinical specimens, with a positive rate of H1N1 as 8.04%. Out of 415 blood samples being collected, the positive rates and the geometric mean titer of H1N1 antibody Mar. 2006 were significantly higher in 0-3, 3-7 and 7-18 year-olds than Oct.2005. CONCLUSION: H1N1 epidemic influenza did occur among children in winter and spring of 2005--2006 in Taiyuan city.

[Distribution and timing of antibody to SARS-CoV in SARS cases of transmission chain or non-transmission chain].

BACKGROUND: To find out the timing of serologic responses after illness onset and distribution of IgG antibody to SARS-CoV in SARS cases of transmission chain or non-transmission chain. METHODS: The IgG and IgM antibodies to SARS-CoV were tested by indirect ELISA in serum samples from 301 clinically diagnosed SARS cases. RESULTS: Totally 158 SARS cases were involved in 15 chains of transmission. The positive rates of SARS-CoV IgG in those chains were 85.70%-100.00% and the overall rate was 94.30% (149/158). The chain of transmission could spread to four generations, but the SARS cases were reduced with increase of generations. There was no significant difference among positive rates of SARS-CoV IgG for generations, Chi square=5.11, P greater than 0.05. The positive rate of SARS-CoV IgG in cases who were not in chain of transmission was 12.59%(18/143) which was statistically significantly different from that of cases in chain of transmission, Chi square=199.64, P less than 0.001. During days 0-7,8-14,15-21,22-30 after onset, the cumulated positive rate of SARS-CoV IgG was 16.67%, 40.00%, 70.00% and 93.10%, respectively, then was kept at the level above 90% and lasted for 217 days. The cumulated positive rate of SARS-CoV IgM during days 0-7 after onset was the same to that of IgG. During days 8-14, 55.17% of cases had seroconversion for IgM which reached a peak (86.96%) during days 21-30. Then the rate rapidly declined. CONCLUSION: More than 94% of cases with SARS could produce IgG antibody when they were infected by SARS-CoV. Detecting SARS-CoV IgG could provide a diagnostic evidence for case confirmation. SARS-CoV IgG appeared as early as 7 days after onset and reached the peak at about weeks 4. Then the high rate of antibody was maintained for more than 6 months.