Atrial Fibrosis and Inflammation in Postoperative Atrial Fibrillation: Comparative Effects of Amiodarone, Colchicine, or Exosomes

Sandrine Parent; Jennifer St Amant; Sophie Van Remortel; Saad Kahn; Ramana Vaka; David Courtman; Duncan John Stewart; Darryl Raymond Davis

doi:10.1016/j.jacep.2024.02.019

Atrial Fibrosis and Inflammation in Postoperative Atrial Fibrillation: Comparative Effects of Amiodarone, Colchicine, or Exosomes

JACC Clin Electrophysiol. 2024 Apr 3:S2405-500X(24)00162-2. doi: 10.1016/j.jacep.2024.02.019. Online ahead of print.

Authors

Sandrine Parent¹, Jennifer St Amant¹, Sophie Van Remortel¹, Saad Kahn², Ramana Vaka¹, David Courtman², Duncan John Stewart³, Darryl Raymond Davis⁴

Affiliations

¹ University of Ottawa Heart Institute, Division of Cardiology, Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada; Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario, Canada.
² Ottawa Hospital Research Institute, Division of Regenerative Medicine, Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
³ Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario, Canada; Ottawa Hospital Research Institute, Division of Regenerative Medicine, Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
⁴ University of Ottawa Heart Institute, Division of Cardiology, Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada; Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario, Canada. Electronic address: ddavis@ottawaheart.ca.

PMID: 38639701
DOI: 10.1016/j.jacep.2024.02.019

Abstract

Background: Extracellular vesicles (EVs) isolated from human heart-derived cells have shown promise in suppressing inflammation and fibroblast proliferation. However, their precise benefits in atrial fibrillation (AF) prevention and the role of their antifibrotic/anti-inflammatory properties remain unclear.

Objectives: The purpose of this study was to conduct a head-to-head comparison of antiarrhythmic strategies to prevent postoperative AF using a rat model of sterile pericarditis. Specifically, we aimed to assess the efficacy of amiodarone (a classic antiarrhythmic drug), colchicine (an anti-inflammatory agent), and EVs derived from human heart-derived cells, which possess anti-inflammatory and antifibrotic properties, on AF induction, inflammation, and fibrosis progression.

Methods: Heart-derived cells were cultured from human atrial appendages under serum-free xenogen-free conditions. Middle-aged Sprague Dawley rats were randomized into different groups, including sham operation, sterile pericarditis with amiodarone treatment, sterile pericarditis with colchicine treatment (2 dose levels), and sterile pericarditis with intra-atrial injection of EVs or vehicle. Invasive electrophysiological testing was performed 3 days after surgery before sacrifice.

Results: Sterile pericarditis increased the likelihood of inducing AF. Colchicine and EVs exhibited anti-inflammatory effects, but only EV treatment significantly reduced AF probability, whereas colchicine showed a positive trend without statistical significance. EVs and high-dose colchicine reduced atrial fibrosis by 46 ± 2% and 26 ± 2%, respectively. Amiodarone prevented AF induction but had no effect on inflammation or fibrosis.

Conclusions: In this study, both amiodarone and EVs prevented AF, whereas treatment with colchicine was ineffective. The additional anti-inflammatory and antifibrotic effects of EVs suggest their potential as a comprehensive therapeutic approach for AF prevention, surpassing the effects of amiodarone or colchicine.

Keywords: atrial fibrillation; exosomes; extracellular vesicles; postoperative.