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      Analysis of immune cell populations in atrial myocardium of patients with atrial fibrillation or sinus rhythm

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          Abstract

          Background

          Atrial fibrillation (AF) is the most common arrhythmia and despite obvious clinical importance remains its pathogenesis only partially explained. A relation between inflammation and AF has been suggested by findings of increased inflammatory markers in AF patients.

          Objective

          The goal of this study was to characterize morphologically and functionally CD45-positive inflammatory cell populations in atrial myocardium of patients with AF as compared to sinus rhythm (SR).

          Methods

          We examined 46 subjects (19 with AF, and 27 in SR) undergoing coronary bypass or valve surgery. Peroperative bioptic samples of the left and the right atrial tissue were examined using immunohistochemistry.

          Results

          The number of CD3+ T-lymphocytes and CD68-KP1+ cells were elevated in the left atrial myocardium of patients with AF compared to those in SR. Immune cell infiltration of LA was related to the rhythm, but not to age, body size, LA size, mitral regurgitation grade, type of surgery, systemic markers of inflammation or presence of diabetes or hypertension. Most of CD68-KP1+ cells corresponded to dendritic cell population based on their morphology and immunoreactivity for DC-SIGN. The numbers of mast cells and CD20+ B-lymphocytes did not differ between AF and SR patients. No foci of inflammation were detected in any sample.

          Conclusions

          An immunohistochemical analysis of samples from patients undergoing open heart surgery showed moderate and site-specific increase of inflammatory cells in the atrial myocardium of patients with AF compared to those in SR, with prevailing population of monocyte-macrophage lineage. These cells and their cytokine products may play a role in atrial remodeling and AF persistence.

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          Most cited references31

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          Electrical, contractile and structural remodeling during atrial fibrillation.

          The natural history of atrial fibrillation (AF) is characterized by a gradual worsening with time. The recent finding that AF itself produces changes in atrial function and structure has provided a possible explanation for the progressive nature of this arrhythmia. Electrical remodeling (shortening of atrial refractoriness) develops within the first days of AF and contributes to an increase in stability of AF. However, 'domestication of AF' must also depend on a 'second factor' since the persistence of AF continues to increase after electrical remodeling has been completed. Atrial contractile remodeling (loss of contractility) leads to a reduced atrial transport function after cardioversion of AF. An important clinical consequence is that during several days after restoration of sinus rhythm, the risk of atrial thrombus formation is still high. In addition, the reduction of atrial contractility during AF may enhance atrial dilatation which may add to the persistence of AF. Tachycardia-induced structural remodeling takes place in a different time domain (weeks to months). Myolysis probably contributes to the loss of atrial contractile force. Although it might explain the loss of efficacy of pharmacological cardioversion and the development of permanent AF, the role of structural remodeling in the progression of AF is still unclear. Atrial structural remodeling also occurs as a result of heart failure and other underlying cardiovascular diseases. The associated atrial fibrosis might explain intra-atrial conduction disturbances and the susceptibility for AF. Thus, both AF itself and the underlying heart disease are responsible for the development of the arrhythmogenic substrate. New strategies for prevention and termination of AF should be build on our knowledge of the mechanisms and time course of AF-induced atrial remodeling.
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            Structural abnormalities in atrial walls are associated with presence and persistency of atrial fibrillation but not with age.

            The purpose of this study was to assess the association between structural changes in human atria, age, and history of atrial fibrillation (AF). Development of fibrosis in atrial walls is associated with deterioration of atrial conduction and predisposes to AF in experiment. Human data, however, are scarce, and whether fibrosis is a cause or consequence of AF is not known. Medical records for consecutive autopsies were checked for AF history and duration. Atrial specimens from 30 patients (ages 64 ± 12 years) were collected in 3 equal age-matched groups as patients without AF history, with paroxysmal AF, or with permanent AF. Tissue samples were obtained at the level of superior pulmonary veins, inferior pulmonary veins, center of posterior left atrial wall, terminal crest, and Bachmann's bundle. Histology sections were assessed for extent of fibrosis, fatty tissues, and inflammatory infiltration at each location. No correlation was observed between age and fibrosis at any location. Fibrosis extent and fatty infiltration were twofold to threefold higher at all locations in patients with history of AF and correlated with lymphomononuclear infiltration. Patients with permanent AF had greater fibrosis extent than did patients with paroxysmal AF. In post-mortem material, structural changes in the atria were not associated with age, but were significantly correlated with presence of AF and its severity. Our findings suggest that age-related changes per se are unlikely to be the sole cause of advanced fibrosis underlying AF. Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
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              HRS/EHRA/ECAS expert Consensus Statement on catheter and surgical ablation of atrial fibrillation: recommendations for personnel, policy, procedures and follow-up. A report of the Heart Rhythm Society (HRS) Task Force on catheter and surgical ablation of atrial fibrillation.

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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                22 February 2017
                2017
                : 12
                : 2
                : e0172691
                Affiliations
                [1 ]Institute of Histology and Embryology, The First Faculty of Medicine, Charles University, Prague, Czech Republic
                [2 ]Institute for Clinical and Experimental Medicine-IKEM, Department of Cardiology, Prague, Czech Republic
                [3 ]Institute for Clinical and Experimental Medicine-IKEM, Department of Cardiovascular Surgery, Prague, Czech Republic
                Centro Cardiologico Monzino, ITALY
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                • Conceptualization: TK JK VM J Pirk.

                • Data curation: TK MB VM.

                • Formal analysis: TK MB VM.

                • Funding acquisition: TK VM JK J Pirk.

                • Investigation: TK NS VM MB MD J Přidal KR.

                • Methodology: JK VM TK.

                • Project administration: TK VM JK J Pirk.

                • Resources: TK VM JK J Pirk.

                • Supervision: TK JK J Pirk.

                • Visualization: NS TK J Přidal KR MD.

                • Writing – original draft: NS TK VM JK.

                • Writing – review & editing: NS TK VM JK.

                Article
                PONE-D-16-41013
                10.1371/journal.pone.0172691
                5321459
                28225836
                f326edb9-dd50-411a-a9ea-630e11325052
                © 2017 Smorodinova et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 20 October 2016
                : 8 February 2017
                Page count
                Figures: 3, Tables: 0, Pages: 13
                Funding
                Funded by: Research Program of Charles University – PRVOUK P25/LF1/2
                Funded by: Ministry of Health for Development of Research Organization 00023001
                Funded by: EU Operational Program Prague—Competitiveness: project CEVKOON (CZ.2.16/3.1.00/22126)
                This work was supported by the Research Program of Charles University – PRVOUK P25/LF1/2 (TK), www.cuni.cz, Ministry of Health for Development of Research Organization 00023001, http://www.mzcr.cz/ (IKEM, institutional support) (JK), and by the EU Operational Program Prague—Competitiveness: project CEVKOON (CZ.2.16/3.1.00/22126), http://www.ikem.cz/cs/centrum-exp-mediciny/cevkoon/a-1676/ (JK, VM). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Medicine and Health Sciences
                Cardiology
                Arrhythmia
                Atrial Fibrillation
                Biology and Life Sciences
                Anatomy
                Cardiovascular Anatomy
                Heart
                Myocardium
                Medicine and Health Sciences
                Anatomy
                Cardiovascular Anatomy
                Heart
                Myocardium
                Biology and Life Sciences
                Immunology
                Immune Response
                Inflammation
                Medicine and Health Sciences
                Immunology
                Immune Response
                Inflammation
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                Diagnostic Medicine
                Signs and Symptoms
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                Pathology and Laboratory Medicine
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                Inflammation
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                Cell Biology
                Cellular Types
                Animal Cells
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                Mast Cells
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                Anatomy
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                Anatomy
                Cardiovascular Anatomy
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                Cardiac Atria
                Medicine and Health Sciences
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