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Severity-dependent atrial remodeling and atrial fibrillation vulnerability in a clinically relevant aortic regurgitation mouse model
Robert Lakin, Xueyan Liu, Dana Sherrard, Mihir Parikh, Ryan Debi, Nazari Polidovitch, Markus J. Duncan, Jian Wu, Peter H. Backx
Robert Lakin, Xueyan Liu, Dana Sherrard, Mihir Parikh, Ryan Debi, Nazari Polidovitch, Markus J. Duncan, Jian Wu, Peter H. Backx
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Research Letter Cardiology Inflammation

Severity-dependent atrial remodeling and atrial fibrillation vulnerability in a clinically relevant aortic regurgitation mouse model

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Abstract

Authors

Robert Lakin, Xueyan Liu, Dana Sherrard, Mihir Parikh, Ryan Debi, Nazari Polidovitch, Markus J. Duncan, Jian Wu, Peter H. Backx

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Figure 1

Graded aortic regurgitation (AR) induces atrial remodeling and atrial fibrillation (AF).

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Graded aortic regurgitation (AR) induces atrial remodeling and atrial fi...
(A) Schematic of AR generation. (B) Graded AR severities (VTIratio) quantified in the aortic arch using Doppler ultrasound. (C) Post-AR mitral inflow changes consistent with restrictive left ventricular (LV) filling. (D) Twenty-four-hour LV systolic and diastolic pressures in Sham (red) and AR (black) mice; 12:12 light/dark cycles indicated. (E) LV end-diastolic pressure (LVEDP) increased immediately after AR, remaining elevated compared with Shams (2-way repeated measures ANOVA with Šidák’s multiple comparison test). (F) Gross morphology and LV M-mode 4 weeks after AR. Scale bars: 1 mm. (G) Changes in LV structural, functional, and hemodynamic indices with VTIratio. (H and I) Atrial electrograms with programmed stimulations showing inducible AF in AR (10/16), but not Sham (0/15) mice. (J) AF durations increased with AR, correlating with VTIratio (gamma generalized linear model, 95% CI shown). (K) Atrial weight–to–tibia length ratio increased in AR versus Sham mice, increasing with VTIratio. (L) Collagen deposition increased in left atrial appendages (LAAs) of AR versus Sham mice (left), with fibrosis increasing with VTIratio (right). Scale bars: 200 μm (×3 magnification) and 100 μm (insets) (×20 magnification). (M) Confocal LAA micrographs showing increased F4/80+ macrophage infiltration (arrows) in AR mice (left), with counts increasing with VTIratio (right). Scale bars: 20 μm (×40 magnification). (N and O) In vivo atrial effective refractory periods (AERPs) and ex vivo action potential durations (80% repolarization) (APD80) were shortened in AR mice. (P) Isochronal activation maps in paced (90 ms) atria revealed conduction slowing with AR. (Q and R) Ex vivo AF inducibility and optically mapped AF episodes were increased in isolated AR atria (5/9) but absent in Sham (0/8) mice. Data presented as mean ± SEM; n values indicated. *P < 0.05 by 2-tailed Student’s t test.

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