title: Effects of chronic atrial fibrillation on active and passive force generation in human atrial myofibrils.
abstract: BACKGROUND
  Chronic atrial fibrillation (cAF) is associated with atrial contractile dysfunction. Sarcomere remodeling may contribute to this contractile disorder.
  
  
  OBJECTIVE
  Here, we use single atrial myofibrils and fast solution switching techniques to directly investigate the impact of cAF on myofilament mechanical function eliminating changes induced by the arrhythmia in atrial myocytes membranes and extracellular components. Remodeling of sarcomere proteins potentially related to the observed mechanical changes is also investigated.
  
  
  RESULTS
  Myofibrils were isolated from atrial samples of 15 patients in sinus rhythm and 16 patients with cAF. Active tension changes following fast increase and decrease in [Ca(2+)] and the sarcomere length-passive tension relation were determined in the 2 groups of myofibrils. Compared to sinus rhythm myofibrils, cAF myofibrils showed (1) a reduction in maximum tension and in the rates of tension activation and relaxation; (2) an increase in myofilament Ca(2+) sensitivity; (3) a reduction in myofibril passive tension. The slow beta-myosin heavy chain isoform and the more compliant titin isoform N2BA were up regulated in cAF myofibrils. Phosphorylation of multiple myofilament proteins was increased in cAF as compared to sinus rhythm atrial myocardium.
  
  
  CONCLUSIONS
  Alterations in active and passive tension generation at the sarcomere level, explained by translational and post-translational changes of multiple myofilament proteins, are part of the contractile dysfunction of human cAF and may contribute to the self-perpetuation of the arrhythmia and the development of atrial dilatation.
authors.affiliation: Center of Molecular Medicine, Department of Physiology, University of Florence, Italy.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Belus
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Piroddi
authors.forename: Cecilia
authors.initials: C
authors.lastname: Ferrantini
authors.forename: Chiara
authors.initials: C
authors.lastname: Tesi
authors.forename: Olivier
authors.initials: O
authors.lastname: Cazorla
authors.forename: Luana
authors.initials: L
authors.lastname: Toniolo
authors.forename: Maurice
authors.initials: M
authors.lastname: Drost
authors.forename: Giulia
authors.initials: G
authors.lastname: Mearini
authors.forename: Lucie
authors.initials: L
authors.lastname: Carrier
authors.forename: Alessandra
authors.initials: A
authors.lastname: Rossi
authors.forename: Alessandro
authors.initials: A
authors.lastname: Mugelli
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Cerbai
authors.forename: Jolanda
authors.initials: J
authors.lastname: van der Velden
authors.forename: Corrado
authors.initials: C
authors.lastname: Poggesi
mesh_terms: D000368:Aged; D001281:Atrial Fibrillation / Q000503:physiopathology*; D002908:Chronic Disease; D005260:Female; D006325:Heart Atria / Q000503:physiopathology; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D009200:Myocardial Contraction / Q000502:physiology; D009206:Myocardium / Q000473:pathology; D032383:Myocytes, Cardiac / Q000473:pathology / Q000502:physiology; D009210:Myofibrils / Q000473:pathology / Q000502:physiology*