title: Pirfenidone mitigates left ventricular fibrosis and dysfunction after myocardial infarction and reduces arrhythmias.
abstract: 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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Cardiac Electrophysiology and Cardiovascular Research Institute, University of California, San Francisco, USA.
authors.forename: Duy T
authors.initials: DT
authors.lastname: Nguyen
authors.forename: Chunhua
authors.initials: C
authors.lastname: Ding
authors.forename: Emily
authors.initials: E
authors.lastname: Wilson
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Marcus
authors.forename: Jeffrey E
authors.initials: JE
authors.lastname: Olgin
mesh_terms: D000818:Animals; D004452:Echocardiography; D022062:Electrophysiologic Techniques, Cardiac; D005355:Fibrosis / Q000517:prevention & control; D006329:Heart Conduction System / Q000503:physiopathology; D006352:Heart Ventricles / Q000473:pathology*; D008297:Male; D009203:Myocardial Infarction / Q000150:complications / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D009431:Neural Conduction; D011728:Pyridones / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017180:Tachycardia, Ventricular / Q000209:etiology / Q000517:prevention & control*; D053773:Transforming Growth Factor beta1 / Q000037:antagonists & inhibitors; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors; D016277:Ventricular Function, Left / Q000187:drug effects*; D020257:Ventricular Remodeling / Q000187:drug effects; D056969:Voltage-Sensitive Dye Imaging
chemical_list: D011728:Pyridones; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; C093844:pirfenidone