Jansen Hailey J, McRae Megan D, Mackasey Martin, Rose Robert A
Libin Cardiovascular Institute, Department of Cardiac Sciences, Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
Front Physiol. 2022 Nov 1;13:1021807. doi: 10.3389/fphys.2022.1021807. eCollection 2022.
Atrial fibrillation (AF) is associated with electrical and structural remodeling in the atria; however, the regional and temporal progression of atrial remodeling is incompletely understood. The objective of this study was to investigate the regional and temporal progression of atrial remodeling leading to changes in AF susceptibility in angiotensin II (Ang II) mediated hypertension. Mice were infused with Ang II for 3, 10 or 21 days. AF susceptibility and atrial electrophysiology were studied using intracardiac electrophysiology. Right and left atrial myocyte electrophysiology was studied using patch-clamping. Atrial fibrosis was assessed histologically. P wave duration and atrial effective refractory period increased progressively from 3 to 21 days of Ang II. AF susceptibility tended to be increased at 10 days of Ang II and was elevated at 21 days of Ang II. Left, but not right, atrial AP upstroke velocity and Na current were reduced at 10 and 21 days of Ang II. Left atrial action potential (AP) duration increased progressively from 3 to 21 days of Ang II due to reductions in repolarizing K current. Right atrial AP prolongation was increased only after 21 days of Ang II. Left and right atrial fibrosis developed progressively from 3 to 21 days, but increases were larger in the left atrium. In conclusion, Ang II mediated atrial electrical and structural remodeling develop earlier and more extensively in the left atrium compared to the right atrium, providing insight into how atrial remodeling leads to enhanced AF susceptibility in Ang II mediated hypertension.
心房颤动（AF）与心房的电重构和结构重构相关；然而，心房重构的区域和时间进程尚未完全明确。本研究的目的是调查在血管紧张素II（Ang II）介导的高血压中，导致AF易感性变化的心房重构的区域和时间进程。给小鼠输注Ang II 3、10或21天。使用心内电生理学研究AF易感性和心房电生理学。使用膜片钳技术研究右心房和左心房心肌细胞的电生理学。通过组织学评估心房纤维化。从Ang II输注3天到21天，P波时限和心房有效不应期逐渐增加。Ang II输注10天时AF易感性有增加趋势，21天时升高。Ang II输注10天和21天时，左心房而非右心房的动作电位（AP）上升速度和钠电流降低。由于复极化钾电流减少，从Ang II输注3天到21天，左心房动作电位（AP）时限逐渐增加。仅在Ang II输注21天后，右心房AP延长增加。从Ang II输注3天到21天，左心房和右心房纤维化逐渐发展，但左心房的增加更大。总之，与右心房相比，Ang II介导的心房电重构和结构重构在左心房更早且更广泛地发生，这为理解心房重构如何导致Ang II介导的高血压中AF易感性增加提供了线索。
