Impact of Short-Term Systemic Hypoxia on Phagocytosis, Cytokine Production, and Transcription Factor Activation in Peripheral Blood Cells

Hypoxia frequently associated with certain physiologic and pathologic conditions influences numerous cellular functions. Because the effects of short-term hypoxia are incompletely understood, we examined phagocytosis and cytokine production as well as the activation of the transcription factors HIF-1 and NFκB in peripheral blood cells of healthy volunteers exposed to an oxygen concentration equivalent to that found at a height of 5500 m. Furthermore, we analysed plasma HIF-1 and serum concentrations of various HIF-1-dependent genes. Results showed that short-term hypoxia increased phagocytosis in neutrophils without affecting monocyte phagocytosis. Hypoxia decreased basal TNFα concentration in monocytes and basal interferon γ concentration in CD4+ T lymphocytes. In contrast, plasma HIF and serum VEGF concentrations were not affected by hypoxia, although serum EPO concentration was raised. In PBMC, hypoxia increased cytosolic HIF-1 concentration without affecting nuclear HIF-1 concentration and led to a rise in the nuclear NFκB in PBMC. Our results show that short-term hypoxia affects immune functions in healthy individuals. Furthermore, we speculate that the effects of hypoxia are not due to HIF-1, but are caused by the activation of NFκB

Cardiotrophin-1 Induces Tumor Necrosis Factor α Synthesis in Human Peripheral Blood Mononuclear Cells

Chronic heart failure (CHF) is associated with elevated concentrations of tumor necrosis factor (TNF) α and cardiotrophin-1 (CT-1) and altered peripheral blood mononuclear cell (PBMC) function. Therefore, we tested whether CT-1 induces TNFα in PBMC of healthy volunteers. CT-1 induced in PBMC TNFα protein in the supernatant and TNFα mRNA in a concentration- and time-dependent manner determined by ELISA and real-time PCR, respectively. Maximal TNFα protein was achieved with 100 ng/mL CT-1 after 3–6 hours and maximal TNFα mRNA induction after 1 hour. ELISA data were confirmed using immunofluorescent flow cytometry. Inhibitor studies with actinomycin D and brefeldin A showed that both protein synthesis and intracellular transport are essential for CT-1 induced TNFα expression. CT-1 caused a dose dependent nuclear factor (NF) κB translocation. Parthenolide inhibited both NFκB translocation and TNFα protein expression indicating that NFκB seems to be necessary. We revealed a new mechanism for elevated serum TNFα concentrations and PBMC activation in CHF besides the hypothesis of PBMC activation by bacterial translocation from the gut

Angiotensin-converting enzyme insertion/deletion polymorphism does not influence the restenosis rate after coronary stent implantation

Background. Experimental studies have shown an activation of the angiotensin-converting enzyme (ACE) system as a response to endothelial injury. Recent publications have elucidated the hypothesis that the ACE gene polymorphism may influence the level of late luminal loss after coronary stent implantation. It is still unclear whether the polymorphism of the angiotensin gene is a major predictor of the extent of neointimal hyperplasia. In this multicenter study, we therefore tested the relationship between the ACE gene polymorphism and the restenosis rate after coronary stent implantation. Methods: As a substudy of the optimization with intracoronary, ultrasound (ICUS) to reduce stent restenosis (OPTICUS) study, we analyzed ACE serum levels and the ACE gene polymorphism in 154 patients at 9 different centers. All patients underwent elective coronary stent implantation in a stenosis of a major coronary vessel. Balloon inflations were repeated until a satisfactory result was achieved in on-line quantitative coronary angiography or ICUS fulfilling the OPTICUS study criteria. After follow-up of 6 months, all patients underwent reangiography tinder identical projections as the baseline procedure. A blinded quantitative analysis of the initial procedure as well as the follow-up examinations were performed by an independent core laboratory. ACE gene polymorphism and ACE serum activity were measured at the 6-month follow-up in a double-blinded setting. Results: With respect to the ACE gene polymorphism, there were three subgroups: DID genotype (48 patients), ID (83 patients) and 11 (23 patients). The subgroups did not differ in regard to age, gender, extent of coronary artery disease, stenosis length, initial degree of stenosis or degree of stenosis after stent implantation. In all, 39 patients (25.3%) had significant restenosis: 12 DD patients (25.0%), 18 ID patients (21.7%) and 9 II patients (39.1%) (odds ratio 2.164, 95% confidence interval 0.853-5.493). We obtained the following results for ACE serum levels: 0.53 mumol/l/s in the DD subgroup, 0.29 mumol/l/s in the ID

Time course of vascular response after an a priori strategy of bare metal stent implantation post-dilated with a paclitaxel-coated balloon: Implementation of a three-dimensional analysis algorithm with optical coherence tomography

Background: An a priori combined therapy of a bare metal stent post-dilated with a paclitaxel- -coated balloon (PCB) was investigated with optical coherence tomography (OCT) at 2 and 6 months regarding vessel response. Previous studies have shown inconsistent results and the time course of vessel healing after such an interventional strategy is unknown. Methods: Thirty-three de novo lesions in 32 patients were electively treated. Six-month OCT analysis was available in 24 lesions. Two-month OCT follow-up was obtained in 16 lesions. Sequential OCT at 2 and 6 months was available in 7 patients. A novel 3-dimensional picture of vessel segments as spread outs was implemented. Results: Severe incomplete stent apposition (ISA) accompanied by significantly lower strut coverage were found at 2-month compared with 6-month follow-up (ISA struts: 11.4 ± 11.8% vs. 1.8 ± 4.8%, p = 0.001; uncovered struts: 14.5 ± 14.8% vs. 2.0 ± 5.3%, p = 0.001). ISA size diminished over time and the possibly observed phenomenon of positive vessel remodeling (remodeling volume: 4.9 ± 5.9 mm3 at 2-months vs. 2.0 ± 2.6 mm3 at 6-months; p = 0.042) was largely reversible in most lesions. Conclusions: Bare metal stenting with adjunctive application of paclitaxel by a coated bal­loon shows transient severe incomplete strut apposition, most likely due to focal positive ves­sel remodeling. Thus, caution is needed in bailout situations following a PCB angioplasty. A novel illustration of OCT parameters as “carpet views” enables a comprehensive analysis of investigated stents.

Spatiotemporal correlation analyses: a new procedure for standardisation of DC magnetocardiograms

There is a lack of standard methods for the analysis of magnetocardiograms (MCGs). MCG signals have a shape similar to the ECG (P wave, QRS complex, T wave). High-quality multichannel recordings can indicate even slight disturbances of de- and repolarisation. The purpose of our study was to apply a new approach in the analysis of signal-averaged DC-MCGs. DC-MCGs (31-channel) were recorded in 182 subjects: 110 patients after myocardial infarction and 72 controls. Spatiotemporal correlation analysis of the QRS complex and T wave patterns throughout the entire heart cycle was used to analyse homogeneity of de- and repolarisation. These plots were compared to standard ECG analyses (electrical axis, Q wave, ST deviation, T polarity and shape). Spatiotemporal correlation analyses seem to be applicable in assessing the course of electrical repolarisation with respect to homogeneity. MCG provided all diagnostic information contained in common ECG recordings at high significance levels. The ECG patterns were included in 5/8 of our parameters for electrical axis, 6/8 for Qwave, 7/8 for ST deviation and 5/8 for T-polarity based on two time series of correlation coefficients. We conclude that our spatiotemporal correlation approach provides a new tool for standardised analysis of cardiac mapping data such as MCG

Determinants of target vessel failure in chronic total coronary occlusions after stent implantation The influence of collateral function and coronary hemodynamics

AbstractObjectivesThe goal of this study was to assess the influence of collateral function, coronary hemodynamics, and the angiographic result on the risk of target vessel failure (TVF) after recanalization of a chronic total coronary occlusion (CTO).BackgroundCollaterals may have an adverse effect on TVF.MethodsIn 111 consecutive patients, a CTO (duration >2 weeks) was successfully recanalized with stent implantation. Collateral function was assessed by intracoronary Doppler flow velocity and pressure recordings distal to the occlusion. Baseline collateral function was determined before the first balloon inflation, and recruitable collateral function after stenting during a balloon reocclusion. Finally, the coronary flow velocity reserve (CFVR) and the fractional flow reserve (FFR) were measured.ResultsAngiographic follow-up after 5 ± 1.4 months in 106 patients showed a reocclusion in 17% and a restenosis in 36%. The major determinants of TVF were the stent length (p < 0.01) and number of implanted stents (p < 0.01). No difference was observed in baseline or recruitable collateral function between patients with and without TVF; 52% of patients had a CFVR ≥2.0, and only 18% a CFVR ≥2.5 after percutaneous transluminal coronary angioplasty, but neither cutoff-value predicted TVF. A low FFR discriminated patients with reocclusion (0.81 ± 0.07 vs. 0.86 ± 0.08, p < 0.05) but not with restenosis (0.87 ± 0.06).ConclusionsThis study showed that there is no relation between a well-developed collateral supply and the risk of TVF in recanalized CTOs. This was rather determined by the stented segment length. There was also no adverse effect of the frequently observed impaired CFVR on TVF, whereas a low FFR was associated with a higher risk of reocclusion

Low HRV entropy is strongly associated with myocardial infarction

Heart rate variability (HRV) is a marker of autonomous activity in the heart. An important application of HRV measures is the stratification of mortality risk after myocardial infarction. Our hypothesis is that the information entropy of HRV, a non-linear approach, is a suitable measure for this assessment. As a first step, to evaluate the effect of myocardial infarction on the entropy, we compared the entropy to standard HRV parameters. The entropy was estimated by compressing the tachogram with Bzip2. For univariate comparison, statistical tests were used. Multivariate analysis was carried out using automatically generated decision trees. The classification rate and the simplicity of the decision trees were the two evaluation criteria. The findings support our hypothesis. The meanNN-normalized entropy is reduced in patients with myocardial infarction with very high significance. One entropy parameter alone exceeds the discrimination strength of multivariate standards-based trees

Termination of atrial flutter by directed transesophageal atrial pacing during transesophageal echocardiography: Terminierung von Vorhofflattern mit gerichteter transösophagealer Vorhofstimulation bei transösophagealer Echokardiographie

Introduction: The purpose of this study was to evaluate termination of atrial flutter (AFL) by directed rapid transesophageal atrial pacing (TAP) with and without simultaneous transesophageal echocardiography (TEE) performed using a novel TEE tube electrode. Materials and methods, and Results: A total of 16 AFL patients (age 63"12 years; 13 males) with mean AFL cycle length of 224"24 ms (ns12) and mean ventricular cycle length of 448"47 ms (ns12) were analyzed using either an esophageal TO electrode (ns10) or a novel TEE tube electrode consisting of a tube with four hemispherical electrodes that is pulled over the echo probe (ns6). AFL could be terminated by directed rapid TAP using an esophageal TO electrode, leading to induction of atrial fibrillation (AF) (ns6), induction of AF and spontaneous conversion to sinus rhythm (SR) (ns3), and with conversion to SR (ns1). AFL could also be terminated by directed rapid TAP using the TEE tube electrode, with induction of AF (ns3) or induction of AF and pontaneous conversion to SR (ns3). Conclusion: AFL can be terminated by directed rapid TAP with hemispherical electrodes with and without simultaneous TEE. TAP with the directed TEE tube electrode is a safe, simple, and useful method for terminating AFL

Detection of Soluble ED-A +

Background and Aims. Fibronectin containing the extra domain A (ED-A+ Fn) was proven to serve as a valuable biomarker for cardiac remodeling. The study was aimed at establishing an ELISA to determine ED-A+ Fn in serum of heart failure patients. Methods. ED-A+ Fn was quantified in serum samples from 114 heart failure patients due to ischemic (ICM, n=44) and dilated (DCM, n=39) cardiomyopathy as well as hypertensive heart disease (HHD, n=31) compared to healthy controls (n=12). Results. In comparison to healthy volunteers, heart failure patients showed significantly increased levels of ED-A+ Fn (p<0.001). In particular in ICM patients there were significant associations between ED-A+ Fn serum levels and clinical parameters, for example, increased levels with rising NYHA class (p=0.013), a negative correlation with left ventricular ejection fraction (p=0.026, r: −0.353), a positive correlation with left atrial diameter (p=0.008, r: 0.431), and a strong positive correlation with systolic pulmonary artery pressure (p=0.002, r: 0.485). In multivariate analysis, ED-A+ Fn was identified as an independent predictor of an ischemic heart failure etiology. Conclusions. The current study could clearly show that ED-A+ Fn is a promising biomarker in cardiovascular diseases, especially in heart failure patients due to an ICM. We presented a valid ELISA method, which could be applied for further studies investigating the value of ED-A+ Fn

Конкурентоспособность фирм в условиях рыночной экономики

Анализ эффективности организации коммерческой деятельности предприятия и оценка конкурентоспособности фирмы. Исследование и разработка системы повышения конкурентоспособности предприятия рынка рекламных услуг.Analysis of the effectiveness of the organization of commercial activities of the enterprise and evaluation of the firm's competitiveness. Research and development of a system for increasing the competitiveness of a service enterprise