Rationale: 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. Methods and 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 [Ca2+] 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 Ca2+ sensitivity; (3) a reduction in myofibril passive tension. The slow β-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.

EFFECTS OF CHRONIC ATRIAL FIBRILLATION ON ACTIVE AND PASSIVE FORCE GENERATION IN HUMAN ATRIAL MYOFIBRILS / A. Belus; N. Piroddi; C. Ferrantini; C. Tesi; O. Cazorla; L. Toniolo; M. Drost; G. Mearini; L. Carrier; A. Rossi; A. Mugelli; E. Cerbai; J. van der Velden; C. Poggesi. - In: CIRCULATION RESEARCH. - ISSN 0009-7330. - STAMPA. - 107(2010), pp. 144-152. [10.1161/CIRCRESAHA.110.220699]

EFFECTS OF CHRONIC ATRIAL FIBRILLATION ON ACTIVE AND PASSIVE FORCE GENERATION IN HUMAN ATRIAL MYOFIBRILS

BELUS, ALEXANDRA ANNA SOPHIE;PIRODDI, NICOLETTA;FERRANTINI, CECILIA;TESI, CHIARA;MUGELLI, ALESSANDRO;CERBAI, ELISABETTA;POGGESI, CORRADO
2010

Abstract

Rationale: 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. Methods and 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 [Ca2+] 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 Ca2+ sensitivity; (3) a reduction in myofibril passive tension. The slow β-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.
107
144
152
A. Belus; N. Piroddi; C. Ferrantini; C. Tesi; O. Cazorla; L. Toniolo; M. Drost; G. Mearini; L. Carrier; A. Rossi; A. Mugelli; E. Cerbai; J. van der Velden; C. Poggesi
File in questo prodotto:
File Dimensione Formato  
AF2010.pdf

Accesso chiuso

Tipologia: Versione finale referata (Postprint, Accepted manuscript)
Licenza: DRM non definito
Dimensione 625.76 kB
Formato Adobe PDF
625.76 kB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in FLORE sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2158/385956
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 38
  • ???jsp.display-item.citation.isi??? 37
social impact