Abstract 12028: Neural Mechanisms of Postoperative Atrial Fibrillation Suppression Using Nanoformulated Calcium Targeting Cardiac Ganglionated Plexi

Abstract

Introduction: The neural mechanisms of postoperative atrial fibrillation (POAF) remain unclear. Hypothesis: We hypothesize that injection of left atrial GP with nanoformulated calcium chloride (nCaCl2) causes GP neuroapoptosis, inhibition of sympathetic and vagal nerve activity (SNA, VNA) and consequent suppression of POAF. Methods: In a novel canine model of POAF with serial bilateral thoracotomy surgeries, we assessed ambulatory SNA and VNA before (baseline), 3-days after and 6-weeks after injection of 1ml of nCaCl2 (n=6) or sham (n=3) into each of 4 left atrial GP. We also serially assessed atrial effective refractory period (AERP) and AF vulnerability (AFV) by in-vivo programmed stimulation before and 6 weeks after nCaCl2 treatment. Results: In this POAF model, postoperative atrial electrical remodeling manifests as a reduction in AERP and increase in AFV from baseline (week 0) to postop (week 3) (Table). Subsequent nCaCl2 treatment at week 3 reversed these changes (increased AERP, decreased AFV) at 6 weeks post-treatment, vs persistently decreased AERP and increased AFV in the sham control group. Three days after nCaCl2 treatment, there was a reduction in SNA and VNA vs baseline and increase in mean and standard deviation (SD) RR intervals vs baseline, whereas the sham group demonstrated the opposite changes (increased SNA, decreased mean RR and SDRR vs baseline). At 6-weeks post-treatment, mean and SDRR remained persistently increased whereas SNA remained suppressed vs baseline. In contrast, SNA remained elevated and mean RR decreased vs baseline in the sham group. Histology demonstrated neuronal apoptosis within GP without atrial myocardial infiltration in nCaCl2-treated but not in sham. Conclusions: Modulation of cardiac GP with nanoformulated calcium causes GP neuroapoptosis, which exerts a persistent sympatho- and parasympatholysis across the cardiac neuraxis, promoting reversed atrial electrical remodeling and durable suppression of POAF.