Abstract 4143906: Prophylactic Administration Of Colchicine Mitigates Atrial Fibrillation Vulnerability Post-Catheter Ablation In Rats: Exploring Sex-Specific Variations.

Background: Atrial Fibrillation (AF) is the most diagnosed cardiac arrhythmia in clinical practice. Catheter ablation (ABLA) is a method used to manage AF by cauterizing the left atrium (LA) to isolate arrhythmogenic areas. However, ABLA is paradoxically associated with atrial inflammation and AF recurrence, with 10% of patients experiencing recurrence within 30 days and over 50% after 12 months. Studies suggest that AF prevalence is generally lower in women than in men, but females with AF are more prone to severe complications. Colchicine has been proposed for its anti-inflammatory and cardioprotective effects. Hypothesis: Early colchicine treatment prevents ABLA-triggered atrial fibrosis, inflammation, and arrhythmogenic substrates. Methods: Male and female Wistar rats (225-275g) were randomly assigned to four groups: Sham or ABLA, with or without colchicine treatment (1 mg/kg/day; intraperitoneally) starting 2 hours before surgery. Sham animals underwent surgery without ABLA. In vivo electrophysiological studies and echocardiography were performed on days 1 (D1) and 3 (D3) post-ABLA. On D3, ex-vivo optical mapping was conducted on Langendorff-perfused hearts, and atrial fibrosis, gene, and protein expression were assessed using Masson's trichrome staining, qPCR, and immunoblotting, respectively. Results: ABLA animals displayed a significantly higher susceptibility to atrial arrhythmias compared to Sham animals, and among ABLA rats, females were 20% less vulnerable to AF than males at D3 post-ABLA. The LA from ABLA rats exhibited significantly slowed conduction velocity, increased fibrosis areas, and enhanced levels of inflammatory markers compared to Sham. Colchicine significantly reduced the incidence of AF post-ABLA with more efficacy in females than males. Moreover, colchicine normalized LA conduction, fibrosis, and inflammation in LA ABLA compared to Sham. Consistent with contemporary knowledge about male and female differences in AF incidence, our data suggest that endogenous female sex hormones combined with colchicine administration may contribute to significantly reducing AF incidence. Conclusion: Initiating Colchicine treatment prior to ABLA may lower post-ABLA-induced LA inflammation and AF occurrence. Delving into the variances in male and female responses to colchicine intervention could offer new insights into addressing post-ABLA AF incidence.Bas du formulaire