Effects of Chronic Atrial Fibrillation on Active and Passive Force Generation in Human Atrial Myofibrils

Center of Molecular Medicine, Department of Physiology, University of Florence, Italy.
Circulation Research (Impact Factor: 11.02). 05/2010; 107(1):144-52. DOI: 10.1161/CIRCRESAHA.110.220699
Source: PubMed


Chronic atrial fibrillation (cAF) is associated with atrial contractile dysfunction. Sarcomere remodeling may contribute to this contractile disorder.
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.
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.
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.

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    • "For investigating contractility ex vivo, a classical approach which is still in use today calls for the direct measurement of myofibril contraction using a cantilever force probe attached to a glass needle mounted on a lever arm of a length control monitor [48]. Another popular technique uses live video-imaging of sarcomere shortening and other parameters in isolated adult cardiomyocytes (e.g. "
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