Effects of Chronic Atrial Fibrillation on Active and Passive Force Generation in Human Atrial Myofibrils
Effects of Chronic Atrial Fibrillation on Active and Passive Force Generation in Human Atrial Myofibrils
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DOI：
10.1161/circresaha.110.220699
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发表时间：
2010-07-09
影响因子：
20.1
通讯作者：
Poggesi, Corrado
中科院分区：
文献类型：
--
作者：
Belus, Alexandra;Piroddi, Nicoletta;Poggesi, Corrado
依据：慢性房颤（cAF）与心房收缩功能障碍相关。肌节重构可能有助于这种contractile disorder.Objective：在这里，我们使用单个心房肌原纤维和快速溶液转换技术直接调查cAF对肌丝机械功能的影响，消除由心房肌细胞膜和细胞外成分的心律失常引起的变化。重塑肌节蛋白可能与所观察到的机械changes.Methods和结果：肌原纤维分离心房样本的15例窦性心律和16例cAF。测定两组肌原纤维[Ca ~（2+）]快速升高和降低后的主动张力变化以及肌节长度与被动张力的关系。与窦性心律肌原纤维相比，cAF肌原纤维显示（1）最大张力和张力激活和舒张速率降低;（2）肌丝Ca 2+敏感性增加;（3）肌原纤维被动张力降低。慢β-肌球蛋白重链亚型和更具顺应性的肌联蛋白亚型N2 BA在cAF肌原纤维中上调。多个肌丝蛋白磷酸化增加cAF相比，窦性心律心房myocardial.Conclusions：在主动和被动的张力产生在肌节水平的改变，解释的翻译和翻译后的变化的多个肌丝蛋白，是人类cAF的收缩功能障碍的一部分，并可能有助于自我永存的心律失常和心房扩张的发展。(Circ Res. 2010; 107：144-152）。
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 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. (Circ Res. 2010; 107: 144-152.)