Background: Post-myocardial infarction (MI) complications include ventricular tachycardia (VT). Excessive non-MI fibrosis, involving the infarct border zone (IBZ) and beyond, is an important substrate for VT vulnerability.
Objective: This study assessed whether the antifibrotic agent pirfenidone can mitigate fibrosis in remodeling and determined its effects on myocardial function and VT susceptibility in a rodent MI model.
Methods: We studied 2 groups of rats undergoing MI 1 week prior to treatment: a control group (n = 15) treated with placebo and a pirfenidone group (n = 15). We performed serial echocardiograms, and after 4 weeks of treatment, we conducted electrophysiological and optical mapping studies as well as histology.
Results: There was less decline in left ventricular (LV) ejection fraction for pirfenidone-treated rats, 8.6% versus 24.3% in controls (P <0.01). Pirfenidone rats also had lower rates of VT inducibility, 28.6% versus 73.3% in control rats (P <0.05). Furthermore, pirfenidone-treated rats had faster conduction velocities in their IBZs compared with controls, at all pacing cycle lengths (P <0.05). Rats treated with pirfenidone also had smaller infarct dense scar (8.9% of LV myocardium vs. 15.7% in controls, P <0.014), less total LV fibrosis (15% vs. 30% in controls, P <0.003), and less nonscar fibrosis (6.6% vs. 12.6% in controls, P <0.006).
Conclusion: Pirfenidone decreased total and nonscar fibrosis in a rat MI model, which correlated with decreased infarct scar, improved LV function, and decreased VT susceptibility. Directly targeting post-MI fibrotic substrates may have a role in limiting infarct-dense scar, improving LV function, and reducing VT vulnerability.
Copyright © 2010 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.