Abstract Body: Introduction: Atrial fibrillation (AF) is the most common sustained arrhythmia in the elderly population. Increased atrial size is a key predictor of AF incidences in older patients, underscoring importance of mechanosensitive ion channels to AF dynamics in the aging atrium linking to AF.
Goal: To characterize excitation wave dynamics in AF in aged rabbit atria and determine the impact of mechanosensitive channel blockers on AF maintenance
Methods: We used optical mapping of ex vivo young (< 1 year) and old rabbit hearts (4~5 year old) and investigated susceptibility to AF under programmed stimulation. Spatial correlation analysis of wave fronts and frequency of AF were analyzed to understand the maintenance mechanisms of AF before and after mechanosensitive ion channel blockers (100 μg/L GsMTx4 targeting piezo channel, and 10 μM IAA-94 targeting volume sensitive chloride channels).
Results: The aged rabbit atria demonstrated larger variations in APD than young, associated with AF inducible spontaneous (n=3/6 vs. 10/160) and S1S2 induced AF(n=8/13 vs. 0/8, panel A). Despite complex wave forms in ECG, activation maps showed AF in the aged rabbit exhibited repetitive patterns of excitation waves, which is further corroborated by spatial correlation analysis (correlation distance = 30 mm in AF vs.7.8 mm in ventricular fibrillation, panel B). Correlation lag maps show both focal and reentry waves co-exist and maintain AF; reentry in LA (57%), reentry in RA (21%), reentry around pulmonary vein (28%), focal from RA and LA appendages (21%), and focal from pulmonary vein (14%). Perfusion of IAA-94 and GsMTx4 reduced AF frequency and AF duration via altering reentry dynamics but not focal activity (panel C), suggesting important roles of mechanically gated channels in AF maintenance.
Conclusion: Aged rabbit atria display distinct electrophysiological remodeling associated with a high propensity for focal activity and reentry formation. Pharmacologic inhibition of mechanosensitive channels reduces AF frequency and duration by reducing reentries highlighting a critical role for mechano electrical coupling in sustaining AF in the aging heart.