title: Splenectomy exacerbates atrial inflammatory fibrosis and vulnerability to atrial fibrillation induced by pressure overload in rats: Possible role of spleen-derived interleukin-10.
abstract: BACKGROUND
  The spleen is important for cardiac remodeling induced by myocardial infarction. However, the role of the spleen in inflammatory atrial fibrosis induced by pressure overload is unknown.
  
  
  OBJECTIVE
  The purpose of this study was to investigate whether splenectomy (SPX) attenuates or exacerbates pressure overload-induced atrial inflammatory fibrosis and vulnerability to atrial fibrillation (AF) in rats.
  
  
  METHODS
  Male Sprague-Dawley rats (6 weeks old) were divided into Sham+Sham, Sham+SPX, abdominal aortic constriction (AAC)+Sham, and AAC+SPX groups, and were evaluated for inflammation, fibrosis, and AF on days 2, 4, 14, and 28.
  
  
  RESULTS
  On day 4, an AAC-induced rise in interleukin-10 (IL-10) level was observed in the spleen, serum, and left atrium (LA), with SPX showing inhibitory effects in the latter 2 instances. In addition, AAC-induced M2 macrophage recruitment into the LA was decreased by SPX, as determined by immunofluorescence labeling (P <.05). On day 28, AAC-induced heterogeneous interstitial fibrosis of the LA was enhanced by SPX (P <.05). Electrophysiologic recordings revealed that the duration of AF and prolongation of interatrial conduction time induced by AAC were increased by SPX (P < .01 and P <.05, respectively). Furthermore, in the AAC+SPX group, the number of macrophages infiltrating into the LA on day 2 was marginal, but increased on day 28 relative to the AAC+Sham group. IL-10 administration attenuated the AAC-induced atrial remodeling that was aggravated by SPX.
  
  
  CONCLUSIONS
  The study results suggest that SPX exacerbates AAC-induced inflammatory atrial fibrosis and increases vulnerability to AF after 4 weeks, likely because of depletion of spleen-derived IL-10.
authors.affiliation: Department of Cardiology and Clinical Examination, Oita University Faculty of Medicine, Oita, Japan.
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Kondo
authors.affiliation: Department of Cardiology and Clinical Examination, Oita University Faculty of Medicine, Oita, Japan. Electronic address: takanao@oita-u.ac.jp.
authors.forename: Naohiko
authors.initials: N
authors.lastname: Takahashi
authors.affiliation: Department of Endocrinology, Metabolism, Rheumatology and Nephrology, Oita University Faculty of Medicine, Oita, Japan.
authors.forename: Koro
authors.initials: K
authors.lastname: Gotoh
authors.affiliation: Department of Cardiology and Clinical Examination, Oita University Faculty of Medicine, Oita, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Fukui
authors.affiliation: Department of Cardiology and Clinical Examination, Oita University Faculty of Medicine, Oita, Japan.
authors.forename: Shotaro
authors.initials: S
authors.lastname: Saito
authors.affiliation: Department of Endocrinology, Metabolism, Rheumatology and Nephrology, Oita University Faculty of Medicine, Oita, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Aoki
authors.affiliation: Department of Cardiology and Clinical Examination, Oita University Faculty of Medicine, Oita, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Kume
authors.affiliation: Department of Cardiology and Clinical Examination, Oita University Faculty of Medicine, Oita, Japan.
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Shinohara
authors.affiliation: Department of Cardiology and Clinical Examination, Oita University Faculty of Medicine, Oita, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Teshima
authors.affiliation: Department of Cardiology and Clinical Examination, Oita University Faculty of Medicine, Oita, Japan.
authors.forename: Tetsunori
authors.initials: T
authors.lastname: Saikawa
mesh_terms: D000818:Animals; D001281:Atrial Fibrillation / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D064752:Atrial Remodeling / Q000502:physiology; D004195:Disease Models, Animal; D005355:Fibrosis; D006325:Heart Atria / Q000473:pathology / Q000503:physiopathology; D007249:Inflammation; D016753:Interleukin-10 / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013154:Spleen / Q000378:metabolism; D013156:Splenectomy / Q000009:adverse effects* / Q000379:methods
chemical_list: D016753:Interleukin-10
keywords: Atrial fibrillation; Fibrosis; Inflammation; Interleukin-10; Pressure overload; Spleen