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大鼠心房颤动时左、右心房心肌细胞收缩功能的腔室间差异。

The inter-chamber differences in the contractile function between left and right atrial cardiomyocytes in atrial fibrillation in rats.

作者信息

Butova Xenia, Myachina Tatiana, Simonova Raisa, Kochurova Anastasia, Mukhlynina Elena, Kopylova Galina, Shchepkin Daniil, Khokhlova Anastasia

机构信息

Institute of Immunology and Physiology, Ural Branch of Russian Academy of Sciences, Yekaterinburg, Russian Federation.

Institute of Natural Sciences and Mathematics, Ural Federal University, Yekaterinburg, Russian Federation.

出版信息

Front Cardiovasc Med. 2023 Aug 7;10:1203093. doi: 10.3389/fcvm.2023.1203093. eCollection 2023.

Abstract

INTRODUCTION

The left and right atria (LA, RA) work under different mechanical and metabolic environments that may cause an intrinsic inter-chamber diversity in structure and functional properties between atrial cardiomyocytes (CM) in norm and provoke their different responsiveness to pathological conditions. In this study, we assessed a LA vs. RA difference in CM contractility in paroxysmal atrial fibrillation (AF) and underlying mechanisms.

METHODS

We investigated the contractile function of single isolated CM from LA and RA using a 7-day acetylcholine (ACh)-CaCl AF model in rats. We compared auxotonic force, sarcomere length dynamics, cytosolic calcium ([Ca]) transients, intracellular ROS and NO production in LA and RA CM, and analyzed the phosphorylation levels of contractile proteins and actin-myosin interaction using an motility assay.

RESULTS

AF resulted in more prominent structural and functional changes in LA myocardium, reducing sarcomere shortening amplitude, and velocity of sarcomere relengthening in mechanically non-loaded LA CM, which was associated with the increased ROS production, decreased NO production, reduced myofibrillar content, and decreased phosphorylation of cardiac myosin binding protein C and troponin I. However, in mechanically loaded CM, AF depressed the auxotonic force amplitude and kinetics in RA CM, while force characteristics were preserved in LA CM.

DISCUSSION

Thus, inter-atrial differences are increased in paroxysmal AF and affected by the mechanical load that may contribute to the maintenance and progression of AF.

摘要

引言

左心房和右心房(LA,RA)在不同的机械和代谢环境下工作,这可能导致正常情况下心房心肌细胞(CM)之间在结构和功能特性上存在内在的腔室间差异,并引发它们对病理状况的不同反应。在本研究中,我们评估了阵发性心房颤动(AF)时左心房与右心房心肌细胞收缩性的差异及其潜在机制。

方法

我们使用大鼠7天乙酰胆碱(ACh)-氯化钙AF模型,研究了从左心房和右心房分离的单个心肌细胞的收缩功能。我们比较了左心房和右心房心肌细胞的辅助张力、肌节长度动态变化、胞质钙([Ca])瞬变、细胞内活性氧(ROS)和一氧化氮(NO)的产生,并使用运动分析方法分析了收缩蛋白的磷酸化水平和肌动蛋白-肌球蛋白相互作用。

结果

心房颤动导致左心房心肌结构和功能变化更为显著,降低了机械无负荷左心房心肌细胞的肌节缩短幅度和肌节再延长速度,这与活性氧产生增加、一氧化氮产生减少、肌原纤维含量降低以及心肌肌球蛋白结合蛋白C和肌钙蛋白I磷酸化减少有关。然而,在机械负荷的心肌细胞中,心房颤动降低了右心房心肌细胞的辅助张力幅度和动力学,而左心房心肌细胞的力特性得以保留。

讨论

因此,阵发性心房颤动时心房间差异增大,且受机械负荷影响,这可能有助于心房颤动的维持和进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/09ba/10440706/ed180787a767/fcvm-10-1203093-g001.jpg

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