Connexin lateralization during Coronary Artery Bypass Graft (CABG) operation: a target for the antiarrhythmic effect of colchicine in the prevention of post-operative atrial fibrillation

Purpose: Post-operative AF (POAF) is a common complication that increases morbidity following CABG. Although statins, propafenone and nitroprusside have reduced POAF none of the studies established a clear link between the pathogenesis of POAF and their favorable effects. Likely, the lack of a mechanistic rationale has impeded these compounds from becoming routine peri-operative practice. Recently the COPPS POAF trial showed that colchicine reduced POAF by almost 50% which was ascribed to its anti-inflammatory effects. Our study focuses on the antiarrhythmic effects of colchicine in POAF. As an increase of connexin heterogeneity harbors arrhythmogenic properties we hypothesized that if connexin lateralization occurs during CABG the pre-operative administration of colchicine might abolish this process by disrupting the microtubule connections between the cytoskeleton and the gap junctions, stabilizing the atrial electrical properties and preventing POAF. Methods: In a double blinded trial 40 patients were randomized to placebo or colchicine administered peri-CABG. Two right atrial appendage (RAA) biopsies were taken; one at the time of cannulation (T0) and the next one hour later (T1). Cx43 immunodetection and confocal microscopy (CLSM) was performed to localize and quantify gap junctions. Dystrophin labeling demarcates the cell borders. ![Figure][1] Results: Preliminary results without colchicine confirm that Cx43 lateralization occurs early during CABG. Figure A: CLSM image of the RAA biopsy (T0). The Cx43-labeled gap junctions (red) are localized near the transversal cell borders, whereas the longitudinal margins mainly show dystrophin (green), B: RAA biopsy from the same patient (T1) showing Cx43 lateralization. This confirms the antiarrhythmic target for colchicine, a study that is currently underway. [1]: pending:yes