Po-01-146 pro-arrhythmic remodelling of the pulmonary vein and left atrial appendage junction in an animal model of endurance exercise

An increased incidence of atrial fibrillation (AF) is observed in endurance athletes but the mechanism underlying this is not fully known. Electrophysiological remodelling of pulmonary vein sleeve myocytes (PV), and the PV to left atrial junction may contribute to arrhythmogenesis. PV-left atrial appendage (LAA) preparations were isolated from male C57BL/6J mice after 6 weeks of treadmill exercise (ExT, running for 2 hours per day at 60-80% maximal oxygen uptake) and compared to age-matched sedentary mice (Sed). Intracellular action potential recordings and high density multielectrode array mapping was performed. Sections were stained for Masson’s trichrome to assess fibrosis. Data are expressed as mean ± standard error. In both groups there was spontaneous activity with burst firing in the PV, that significantly increased on superfusion with 10 micromolar noradrenaline (NA). There was more frequent burst activity in ExT PV (n=8/10; inter-burst time Sed 14.7 ± 8.4 s vs. ExT 4.9 ± 1.2 s; p<0.01) and programmed electrical stimulation from the right superior PV (rsPV) ostium at 20 Hz induced PV firing bursts with a shorter cycle length in ExT (n=5/5, Sed 313 ± 53 ms vs. ExT 223 ± 37 ms, p=0.05). NA induced a shift in the site of earliest activation from rsPV towards PV-LAA junction in 50% of ExT preparations vs. 25% in Sed (n=8/9). Conduction velocity (CV) at the PV-LAA junction was slowed by 65% in ExT (n=8/9, Sed 1.10 ± 0.26 m/s vs. ExT 0.39 ± 0.08 m/s, p<0.05) and CV from the site of earliest activation toward LAA within the PV was slowed (Sed 0.46 ± 0.10 m/s vs. ExT 0.20 ± 0.03 m/s, p<0.05) in ExT. Increased collagen deposition was seen the ExT PV-LAA junction vs. Sed (n =3/5; Sed 23 ± 4% vs. ExT 37 ± 1%, p<0.01). Exercise training caused alterations to the PV electrical susbtrate with an observed increase in burst frequency and reduction in cycle length in trained mice. There was also conduction slowing in the PVs and PV-LA junction of trained animals with evidence of increased collagen deposition. These data provide new insight into the electroanatomical substrate that predisposes athletes to AF.