Pirfenidone mitigates left ventricular fibrosis and dysfunction after myocardial infarction and reduces arrhythmias.
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.
Nguyen
Duy T
DT
Cardiac Electrophysiology and Cardiovascular Research Institute, University of California, San Francisco, USA.
Ding
Chunhua
C
Wilson
Emily
E
Marcus
Gregory M
GM
Olgin
Jeffrey E
JE
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
D011728:Pyridones; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; C093844:pirfenidone