1,720,979 research outputs found
Increased Sympathetic Nerve Activity in COPD is Associated with Morbidity and Mortality
Chronic obstructive lung disease (COPD) is a major cause of comorbidity and mortality. Systemic effects, such as sympathetic activation, might contribute to progression and severity of the disease. This study investigated whether increased sympathetic activity is associated with increased long-term morbidity and mortality with COPD. Following a baseline registration of muscle sympathetic nerve activity (MSNA), 21 COPD patients and 21 matched healthy control subjects were contacted after a mean follow-up period of 7 years. Information about the number of hospitalizations during follow-up was obtained from patients who were still alive. Information about the time of death was collected from relatives of the deceased and local registration offices. The primary endpoint was the comparison of MSNA in living patients without hospitalizations versus MSNA in the patients who died or had at least one hospitalization due to exacerbation of COPD. At baseline, MSNA was significantly increased, whereas forced expiratory volume in 1 s and arterial oxygen tension (PaO2) were significantly decreased in patients compared with controls. MSNA was significantly higher in COPD patients who had reached the combined endpoint of hospitalization or death during follow-up (n = 12) compared with patients who were still alive at follow-up and had not been hospitalized (n = 8): 60.3 +/- A 15.8 (SD) bursts/min versus 40.5 +/- A 17.5 bursts/min; p = 0.022. Our data suggest that sympathetic activation is related to adverse outcome in COPD. Although this finding has to be replicated in larger studies, it implies that neurohumoral activation could be a potential therapeutic target in COPD
First experience with a new tool for automatic mapping of fragmented signals in a case report of cardioneuroablation
The role and regulation of Moraxella catarrhalis-induced human beta-defensin 3 expression in human pulmonary epithelial cells
Background: Bacterial colonisation with Moraxella catarrhalis may partly sustain chronic inflammation in the lower airways of patients with chronic obstructive pulmonary disease (COPD). In addition, this bacterium causes infectious exacerbations of COPD, which often necessitate treatment with antibiotics. Antimicrobial peptides are the body's own antibiotic substances with bactericidal and bacteriostatic, as well as immunomodulatory function. In particular, human beta-defensin 3 (hBD-3) exerts an antimicrobial effect against an extraordinarily broad spectrum of pathogens. We therefore investigated the role of hBD-3 in infections of pulmonary epithelial cells with M. catarrhalis. Methods: The antimicrobial activity of hBD-3 vs. M. catarrhalis was evaluated in an antimicrobial susceptibility assay. We analyzed hBD-3 secretion of M. catarrhalis-infected pulmonary epithelial cells using ELISA. The role of M. catarrhalis-specific virulence factors, toll-like receptors (TLR) 2 and 4, MAPK pathways, and transcription factors AP-1 and NF-kappa B in the induction and regulation of hBD-3 expression were explored with specific inhibitors, small interference RNA, Western Blot, and chromatin immunoprecipitation (ChIP) assays. Results: HBD-3 exhibited a strong bactericidal effect against M. catarrhalis. M. catarrhalis induced hBD-3 expression in pulmonary epithelial cells, which was dependent on M. catarrhalis membranous lipoolygosaccharide (LOS), while the surface proteins UspA1 and UspA2 were not involved. Gene silencing of TLR2, but not TLR4, led to a reduced hBD-3 secretion after stimulation with M. catarrhalis or M. catarrhalis LOS. Inhibition of MAPKs ERK1/2 and JNK, but not p38, reduced hBD-3 secretion. HBD-3 expression was mediated through the recruitment of AP-1 to the hBD-3 gene promoter and was independent of NF-kappa B. Conclusion: The immune response of pulmonary epithelial cells towards M. catarrhalis involves secretion of hBD-3, which has a bactericidal effect against this pathogen. Binding of M. catarrhalis virulence factor LOS to TLR2 causes an ERK1/2- and JNK-dependent induction of AP-1-related transcription of the hBD-3 gene, resulting in the production and secretion of hBD-3. (C) 2015 Published by Elsevier Inc
Comparison between contrast-guided and pressure-guided ablation using the novel pressure visualization tool for cryoballoon pulmonary vein isolation
Abstract During cryoballon pulmonary vein isolation (PVI) complete occlusion of the pulmonary vein ostia during the freeze cycles is mandatory. Typically, PV occlusion is assessed by contrast injection under fluoroscopy. Using an update for the Cryo Console it is possible to directly visualize occlusion pressure as an indicator of complete PV occlusion during cryoballoon procedures. In this study, we compared PV pressure monitoring during cryoballoon PVI to a conventional approach regarding procedural outcomes. We retrospectively analysed the procedural data of 50 patients (25 patients with pressure-guided PVI and 25 patients with contrast-guided PVI) treated with cryoballoon PVI in our centre. Complete PV occlusion in the pressure-guided group was defined as an abrupt change in the pressure waveform with a loss of the a-wave after advancing the cryoballoon to the PV ostium. We observed comparable results regarding procedural time, left atrial dwell time or fluoroscopy time when comparing the pressure guided to our conventional approach. Moreover, there were no differences regarding acute procedural effectivity or freeze cycle characteristics. As expected, a significant reduction of contrast use was achieved in the pressure measurement group (10.4 vs. 25.5 ml, p < 0.0001). Monitoring complete PV occlusion by visualizing the occlusion pressure is feasible. Acute procedural outcome was comparable to our standard approach using contrast injection to verify complete PV occlusion. Most importantly, a significant reduction in contrast use could be achieved which has to be confirmed in larger patient cohorts
The Moraxella catarrhalis-induced pro-inflammatory immune response is enhanced by the activation of the epidermal growth factor receptor in human pulmonary epithelial cells
AbstractBackgroundChronic lower airway inflammation is considered to be a major cause of pathogenesis and disease progression in chronic obstructive pulmonary disease (COPD). Moraxella catarrhalis is a COPD-associated pathogen causing exacerbations and bacterial colonization in the lower airways of patients, which may contribute to chronic inflammation. Increasing evidence suggests that the epidermal growth factor receptor (EGFR) modulates inflammatory processes in the human airways. The goal of this study was to investigate the role of EGFR in the M. catarrhalis-induced pro-inflammatory immune response in airway epithelial cells.MethodsThe effects of inhibition and gene silencing of EGFR on M. catarrhalis-dependent pro-inflammatory cytokine expression in human primary bronchial epithelial cells (NHBEs), as well as the pulmonary epithelial cell lines BEAS-2B and A549 were analyzed. We also assessed the involvement of EGFR-dependent ERK and NF-κB signaling pathways.ResultsThe M. catarrhalis-induced pro-inflammatory immune response depends, at least in part, on the phosphorylation and activation of the EGF receptor. Interaction of M. catarrhalis with EGFR increases the secretion of pro-inflammatory cytokines, which is mediated via ERK and NF-κB activation.ConclusionThe interaction between M. catarrhalis and EGFR increases airway inflammation caused by this pathogen. Our data suggest that the inhibition of EGFR signaling in COPD could be an interesting target for reducing M. catarrhalis-induced airway inflammation
Impact of Non-Invasive Ventilation on Sympathetic Nerve Activity in Chronic Obstructive Pulmonary Disease
Purpose Chronic obstructive pulmonary disease (COPD) is associated with elevated sympathetic nerve activity, which is probably linked to an increased cardiovascular risk, and may contribute to muscle dysfunction by heightened muscle vasoconstrictor drive. We hypothesized that resistive unloading of respiratory muscles by intermittent non-invasive ventilation (NIV) reduces sympathetic tone at rest and during subsequent handgrip exercise in patients with COPD. Methods Muscle sympathetic nerve activity (MSNA) in the peroneal nerve, heart rate, blood pressure, CO2, and SpO2 were continuously recorded in 5 COPD patients with intermittent NIV and 11 control COPD patients without NIV. Static and dynamic handgrip exercises were performed before and after NIV. Results At baseline, heart rate-adjusted MSNA (bursts/100 heart beats) did not differ between groups. NIV did not significantly affect MSNA levels at rest. However, during handgrip exercises directly following NIV, MSNA was lower than before, which was significant for dynamic handgrip (67.00 ± 3.70 vs. 62.13 ± 4.50 bursts/100 heart beats; p = 0.035 in paired t test). In contrast, MSNA (non-significantly) increased in the control group during repeated dynamic or static handgrip. During dynamic handgrip, tCO2 was lower after NIV than before (change by −5.04 ± 0.68 mmHg vs. −0.53 ± 0.64 in the control group; p = 0.021), while systolic and diastolic blood pressure did not change significantly. Conclusions NIV reduces sympathetic activation during subsequent dynamic handgrip exercise and thereby may elicit positive effects on the cardiovascular system as well as on muscle function in patients with COPD
Next-generation atrial fibrillation ablation: clinical performance of pulsed-field ablation and very high-power short-duration radiofrequency
Abstract Introduction Pulsed-field energy (PFA) and very high-power short-duration radiofrequency (vHPSD-RF) are two novel ablation methods for pulmonary vein isolation (PVI). Both PFA and vHPSD-RF show promise for improving efficacy, safety, and reducing procedure durations. However, direct comparisons between these two techniques are scarce. Methods and results Retrospective analysis of 82 patients with symptomatic AF. Of these, 52 patients received PFA and 30 received vHPSD-RF (90 W, 4 s) as index procedure. At the 6-month follow-up, AF recurrence occurred in 4 patients following PFA and 5 patients following vHPSD-RF ( p -value = 0.138). Significant improvements in the EHRA and NYHA stages were evident in both PFA ( p < 0.001 and p = 0.047, respectively) and vHPSD-RF groups ( p = 0.007 and p = 0.012, respectively). The total procedure duration and the left atrial dwell time were significantly shorter in the PFA group (64 ± 19 min vs. 99 ± 32 min, p < 0.001 and 41 ± 12 min vs. 62 ± 29 min, p < 0.001, respectively). The fluoroscopy time and dose area product were significantly higher in PFA (14 ± 6 vs. 9 ± 5 min, p < 0.001 and 14 ± 9 vs. 11 ± 9 Gy cm 2 , p = 0.046, respectively). One patient in the vHPSD-RF group suffered a stroke, not directly linked to the procedure (0 vs. 1 major complication, p = 0.366). Conclusion Based on this retrospective single-center study, PFA and vHPSD-RF were associated with similar effectiveness and safety profiles. PFA was linked to shorter procedure times and higher radiation exposure compared to vHPSD-RF. Graphical Abstrac
Contact force sensing manual catheter versus remote magnetic navigation ablation of atrial fibrillation: a single-center comparison
Abstract
Background
Data comparing remote magnetic catheter navigation (RMN) with manual catheter navigation in combination with contact force sensing (MCN-CF) ablation of atrial fibrillation (AF) is lacking. The primary aim of the present retrospective comparative study was to compare the outcome of RMN versus (vs.) MCN-CF ablation of AF with regards to AF recurrence. Secondary aim was to analyze periprocedural risk, ablation characteristics and repeat procedures.
Methods
We retrospectively analyzed 452 patients undergoing a total of 605 ablations of AF: 180 patients were ablated using RMN, 272 using MCN-CF.
Results
Except body mass index there was no significant difference between groups at baseline. After a mean 1.6 ± 1.6 years of follow-up and 1.3 ± 0.4 procedures, 81% of the patients in the MCN-CF group remained free of AF recurrence compared to 53% in the RMN group (
P
< 0.001). After analysis of 153 repeat ablations (83 MCN-RF vs. 70 RMN;
P
= 0.18), there was a significantly higher reconnection rate of pulmonary veins after RMN ablation (
P
< 0.001). In multivariable Cox-regression analysis, RMN ablation (
P
< 0.001) and left atrial diameter (
P
= 0.013) was an independent risk factor for AF recurrence. Procedure time, radiofrequency application time and total fluoroscopy time and fluoroscopy dose were higher in the RMN group without difference in total number of ablation points. Complication rates did not differ significantly between groups (
P
= 0.722).
Conclusions
In our retrospective comparative study, the AF recurrence rate and pulmonary vein reconnection rate is significantly lower with more favorable procedural characteristics and similar complication rate utilizing MCN-CF compared to RMN
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