Stationary and Recurrent Properties of Atrial Fibrillation Conduction Patterns in Goat

Introduction. Electrical mapping of the atria is used to assess the substrate of atrial fibrillation (AF). Targeted ablation of the AF substrate assumes spatiotemporal stationarity. In this study we analyzed long AF recordings of AF using high-density contact mapping.Methods. In 12 goats with stable AF 10 successive 60s files were recorded, within a single AF episode. AF cycle length, fractionation index (FI), lateral dissociation, conduction velocity, breakthroughs and preferentiality of conduction (Prefi were assessed to construct AF-property maps. The Pearson correlation coefficient (PCC) between AF-property maps of consecutive recordings was calculated. Recurrence plots and recurrence quantification analysis were used to identify recurrent patterns.Results Spatiotemporal stationarity for the 6 properties were high, PCC ranged from 0.66 +/- 0.11 for Pref to 0.98 +/- 0.01 for FI. The PCC is not affected by the time delay between files. Yet, highly dynamic patterns were found. Recurrence plots revealed few (1.6 +/- 0.7) recurrent patterns in individual animals.Conclusions AF properties were stationary in stable AF. This cannot be attributed to stable recurrent conduction patterns. during This suggests that spatial properties of the atrium determine AF properties

Physical and Pharmacological Restraints in Hospital Care:Protocol for a Systematic Review

Background: Physical and pharmacological restraints, defined as all measures limiting a person in his or her freedom, are extensively used to handle unsafe or problematic behavior in hospital care. There are increasing concerns as to the extent with which these restraints are being used in hospitals, and whether their benefits outweigh their potential harm. There is currently no comprehensive literature overview on the beneficial and/or adverse effects of the use of physical and pharmacological restraints in the hospital setting. Methods: A systematic review of the existing literature will be performed on the beneficial and/or adverse effects of physical and pharmacological restraints in the hospital setting. Relevant databases will be systematically searched. A dedicated search strategy was composed. A visualization of similarities (VOS) analysis was used to further specify the search. Observational studies, and if available, randomized controlled trials reporting on beneficial and/or adverse effects of physical and/or pharmacological restraints in the general hospital setting will be included. Data from included articles will be extracted and analyzed. If the data is suitable for quantitative analysis, meta-analysis will be applied. Discussion: This review will provide data on the beneficial and/or adverse effects of the use of physical and pharmacological restraints in hospital care. With this review we aim to guide health professionals by providing a critique of the available evidence regarding their choice to either apply or withhold from using restraints. A limitation of the current review will be that we will not specifically address ethical aspects of restraint use. Nevertheless, the outcomes of our systematic review can be used in the composition of a multidisciplinary guideline. Furthermore, our systematic review might determine knowledge gaps in the evidence, and recommendations on how to target these gaps with future research. Systematic Review Registration: PROSPERO registration number: CRD42019116186

Coagulation Factor Xa Induces Proinflammatory Responses in Cardiac Fibroblasts via Activation of Protease-Activated Receptor-1

Coagulation factor (F) Xa induces proinflammatory responses through activation of protease-activated receptors (PARs). However, the effect of FXa on cardiac fibroblasts (CFs) and the contribution of PARs in FXa-induced cellular signalling in CF has not been fully characterised. To answer these questions, human and rat CFs were incubated with FXa (or TRAP-14, PAR-1 agonist). Gene expression of pro-fibrotic and proinflammatory markers was determined by qRT-PCR after 4 and 24 h. Gene silencing of F2R (PAR-1) and F2RL1 (PAR-2) was achieved using siRNA. MCP-1 protein levels were measured by ELISA of FXa-conditioned media at 24 h. Cell proliferation was assessed after 24 h of incubation with FXa ± SCH79797 (PAR-1 antagonist). In rat CFs, FXa induced upregulation of Ccl2 (MCP-1; >30-fold at 4 h in atrial and ventricular CF) and Il6 (IL-6; ±7-fold at 4 h in ventricular CF). Increased MCP-1 protein levels were detected in FXa-conditioned media at 24 h. In human CF, FXa upregulated the gene expression of CCL2 (>3-fold) and IL6 (>4-fold) at 4 h. Silencing of F2R (PAR-1 gene), but not F2RL1 (PAR-2 gene), downregulated this effect. Selective activation of PAR-1 by TRAP-14 increased CCL2 and IL6 gene expression; this was prevented by F2R (PAR-1 gene) knockdown. Moreover, SCH79797 decreased FXa-induced proliferation after 24 h. In conclusion, our study shows that FXa induces overexpression of proinflammatory genes in human CFs via PAR-1, which was found to be the most abundant PARs isoform in this cell type

Ruimtelijke en stedelijke ontwikkelingen na 1984 : de nieuwe welvaart van de Randstad en haar prijs. De ruimtelijke toekomst van Nederland.

Includes bibliographies.De nieuwe welvaart van de Randstad en haar prijs / A. Verbaan, H. Puylaert, J. van Staalduine.De ruimtelijke toekomst van Nederland / H.J. van Hunnik

Antiarrhythmic effect of vernakalant in electrically remodeled goat atria is caused by slowing of conduction and prolongation of postrepolarization refractoriness

Vernakalant inhibits several potassium currents and causes a rate- and voltage-dependent inhibition of the sodium current.The aim of this study was to evaluate the antiarrhythmic mechanism of vernakalant in normal and electrically remodeled atria.Fourteen goats were instrumented with electrodes on both atria. Drug effects on refractory period (ERP), conduction velocity (CV), and atrial fibrillation cycle length (AFCL) were determined in normal goats (control) and after 2 (2dAF) or 11 (11dAF) days of pacing-induced atrial fibrillation (AF) in awake goats. To evaluate the contribution of changes in conduction and ERP, the same experiments were performed with flecainide and AVE0118. In a subset of goats, monophasic action potentials were recorded during anesthesia.Vernakalant dose-dependently prolonged ERP and decreased CV in CTL experiments. Both effects were maintained after 2dAF and 11dAF. After 11dAF, conduction slowed down by 8.2 ± 1.5 cm/s and AFCL increased by 55 ± 3 ms, leading to AF termination in 5 out of 9 goats. Monophasic action potential measurements revealed that ERP prolongation was due to enhanced postrepolarization refractoriness. During pacing, vernakalant had comparable effects on CV as flecainide, while effect on ERP was comparable to AVE0118. During AF, all compounds had comparable effects on median AFCL and ERP despite differences in their effects on CV during pacing.The antiarrhythmic effect of vernakalant in the goat, at clinically relevant plasma concentrations, is based on both conduction slowing and ERP prolongation due to postrepolarization refractoriness. These electrophysiological effects were not affected by long-term electrical remodeling of the atria.Arnevan Hunnik, Dennis H.Lau, Stef Zeemering, Marion Kuiper, Sander Verheule, Ulrich Schotte