Abstract 9743: Profibrillatory Atrial Autonomic and Cellular Electrophysiological Remodelling with Endurance Training

Abstract

Background: Endurance exercise (Ex) increases AF risk, but underlying mechanisms are unknown. Here, we studied Ex induced autonomic and cellular electrophysiological changes controlling AF risk. Methods: Ex rats (daily treadmill training X 16 wks) were compared to matched sedentary (Sed) controls. Parasympathetic and sympathetic tone were assessed from heart rate (HR) changes caused by atropine and propranolol respectively. Baroreflex sensitivity was studied by HR responses to phenylephrine-induced BP changes. Ion currents (I KACh , I to , I CaL ) were measured in atrial myocytes by patch clamp. Atrial refractory period (ARP) was measured in vivo with transvenous electrode catheters. mRNA expression was quantified by qPCR. Results: Atrial myocytes were hypertrophied in Ex (129±8.7 pF vs 73±5 pF Sed, p<0.001). Parasympathetic tone was significantly enhanced in Ex rats by 83%, with no changes in sympathetic tone. Reflex vagal sensitivity was enhanced (60% increase in HR-reduction vs BP-increase slope with phenylephrine boluses). Post-synaptic responses were also increased, as shown by significant increases in I KACh induced by 100 μ M acetylcholine, ACh (Fig. A). mRNA expression of beta-adrenergic (β1, β2) and muscarinic (M2, M3) receptors and associated G proteins did not differ between groups. Regulatory G signaling proteins (RGS, Fig. B), which decrease ACh responses, were downregulated in Ex. Balanced downregulation of voltage gated K + and Ca 2+ current subunits (Fig. C) and currents (Fig. D) left ARP unchanged in the absence of ACh. AF inducibility was enhanced in Ex rats, an effect that was abolished by atropine. Conclusions: Ex promotes AF by enhancing vagal tone through pre (baroreflex) and post (RGS, I KACh ) synaptic mechanisms. Ion channel expression changes in a balanced way, leaving repolarization unaffected in the absence of ACh.