Pirfenidone Prevents the Development of a Vulnerable Substrate for Atrial Fibrillation in a Canine Model of Heart Failure

• DOI: 10.1161/circulationaha.106.624320
• Publication Date: 2006-10-10T01:02:02Z
• Authors: Ken W. Lee; Thomas H. Everett; Dulkon Rahmutula; Jose M. Guerra; Emily Wilson; Chunhua Ding; Jeffrey E. Olgin
• Keywords: Pirfenidone; Interquartile range

Background— Atrial fibrosis is an important substrate in atrial fibrillation (AF), particularly the setting of structural heart disease. In a canine model, congestive failure (CHF) produces significant and for sustained AF. This remodeling potential therapeutic target. The objective present study to evaluate effects antifibrotic drug pirfenidone (PFD) on arrhythmogenic CHF model. Methods Results— We studied 15 canines, divided equally into 3 groups: control, canines not treated with PFD, PFD. was induced by ventricular tachypacing (220 bpm weeks), oral PFD administered 3-week pacing period. performed electrophysiology AF vulnerability studies, measurements, cytokine expression studies. Only untreated group developed (>30 minutes, 4 5 canines; P <0.05). Treatment resulted attenuation left remodeling, reduction conduction heterogeneity index (median [25% 75% interquartile range] 4.96 [3.53 5.64] versus 2.52 [2.11 2.82], <0.01; cycle length 300 ms), (16.0% [13.0% 17.5%] 8.7% [5.7% 10.6%], <0.01), duration (1800 [1020 1800] seconds 6 [5 22] seconds, <0.01). Immunoblotting studies demonstrated drug’s multiple cytokines, including transforming growth factor-β1 expression. Conclusions— results significantly reduced vulnerability. Pharmacological therapy targeted at fibrotic itself may play role management