Regional and temporal progression of atrial remodeling in angiotensin II mediated atrial fibrillation

Abstract

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 in vivo 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.

Overview of programmed electrical stimulation to assess atrial fibrillation susceptibility in mice

“…The initial 2 s burst had a CL of 40 ms and a pulse width of 5 ms while the second and third bursts had CLs of 20 ms with pulse widths of 5 and 10 ms, respectively. A subsequent modification of this protocol was the addition of two 100 beat trains delivered at 20–25 ms pulse widths after the third 2 s burst ( Jansen et al, 2022 ).…”