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

<div><p>Background</p><p>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.</p><p>Objective</p><p>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).</p><p>Methods</p><p>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.</p><p>Results</p><p>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.</p><p>Conclusions</p><p>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.</p></div

CD45-positive cells in the atrial myocardium.

<p>Sections of atrial wall from patients with sinus rhythm (A, B, D) and atrial fibrillation (C) showing a result of immunoperoxidase reaction for CD45. A) Epicardial and myocardial layer of atrial wall contains scattered as well as clustered (arrowhead) CD45-positive cells. Scale bar = 100μm. B) Endocardial layer with CD45-positive cells (arrowhead) next to the atrial lumen (L). Scale bar = 20μm. C) A section through the trabecular part of the atrial wall with CD45-positive cells in the myocardium (M) and endocardium (E). Scale bar = 50 μm. D) A detailed view on the atrial myocardium with CD45-positive cells having rather rounded (arrowhead) or elongated (arrow) cell shape. Scale bar 50 = μm. E) Frequency of CD45+ cells in the atrial myocardium of patients with atrial fibrillation (AF) and sinus rhythm (SR). An average number of CD45+ cells per square mm of cross-sectioned atrial myocardium is given +- SD. Right appendage–SR (n = 22), AF (n = 15); Left appendage—SR (n = 8), AF (n = 8); Left atrial free wall—SR (n = 4), AF (n = 8); Left atrial free wall + left appendage—SR (n = 12), AF (n = 16).</p

CD3-positive T-lymphocytes and CD68-KP1-positive cells in the atrial myocardium.

<p>Sections of atrial myocardium from patients with atrial fibrillation showing a result of immunoperoxidase reaction for CD3 and CD68-KP1. A) CD3-positive T-lymphocytes localized among atrial cardiomyocytes and in the interstitial spaces (arrowheads). Scale bar = 50 μm. B) CD68-KP1-positive cells are found in the interstitium and have mainly elongated morphology (arrowheads). Scale bar = 50 μm. C) Frequency of CD3-positive T-lymphocytes in the atrial myocardium of patients with atrial fibrillation (AF) and sinus rhythm (SR). An average number of CD3-positive T-lymphocytes cells per square mm of cross-sectioned atrial myocardium is given +- SD. Right appendage–SR (n = 17), AF (n = 11); Left appendage—SR (n = 8), AF (n = 10); Left atrial free wall + left appendage—SR (n = 9), AF (n = 16). *—p<0,05 D) Frequency of CD68-KP1-positive cells in the atrial myocardium of patients with atrial fibrillation (AF) and sinus rhythm (SR). An average number of CD68-KP1-positive cells per square mm of cross-sectioned atrial myocardium is given +- SD. Right appendage–SR (n = 22), AF (n = 9); Left appendage—SR (n = 11), AF (n = 9); Left atrial free wall + left appendage—SR (n = 13), AF (n = 19). *—p<0,05</p