PO-01-159 ROLE OF THE SUCCINATE PATHWAY IN ATRIAL FIBRILLATION MECHANISMS

Atrial fibrillation (AF) is the most common arrhythmia and associated with increased morbidity mortality. The mechanisms underlying transition from paroxysmal to persistent AF are still a matter of debate. Recent studies indicate potential role for metabolic remodelling in stabilization process levels specific substrate, succinate, have been found blood plasma patients. While succinate known increase reactive oxygen species (ROS) production, receptor (GPR91) atrial function unknown. To assess impact pathway on vulnerability sheep model. GPR91 expression were quantified by Western Blot (WB) previously described model induced burst-pacing. Optical experiments subsequently performed ex vivo right atria (RA) control (N=5). RA perfused Tyrode solution, then supplemented cis-epoxysuccinic acid (cESA), activator (150μM) study its involvement electrophysiology AF. Action duration at 80% repolarization (APD80) assessed 2 5Hz pacing frequency. We used an S1S2 protocol determine effective refractory period (ERP) burst (30Hz) vulnerability. Finally, organ donation program allowed us investigate these properties human patient. WB revealed compared sham sheep. Interestingly, resistant (no after 90 days pacing), decreased sham. During cESA perfusion RA, sinus rhythm (119 vs 95 bpm; p=0,03) ERP (202 178 ms; p=0,36) when baseline. also observed decrease APD80 (199 177 p=0.009) CV (127 115 cm/sec; p=0.01). These electrophysiological perturbations led (0% 60%) spontaneous arrhythmias. results corroborated (265 241 ms), (240 220 94 cm/sec) For first time, we demonstrated that expressed tissue activation through can play major mechanisms.