Effects of chronic atrial fibrillation on active and passive force generation in human atrial myofibrils.
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.
Belus
Alexandra
A
Center of Molecular Medicine, Department of Physiology, University of Florence, Italy.
Piroddi
Nicoletta
N
Ferrantini
Cecilia
C
Tesi
Chiara
C
Cazorla
Olivier
O
Toniolo
Luana
L
Drost
Maurice
M
Mearini
Giulia
G
Carrier
Lucie
L
Rossi
Alessandra
A
Mugelli
Alessandro
A
Cerbai
Elisabetta
E
van der Velden
Jolanda
J
Poggesi
Corrado
C
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*