Table 1: Results from Preclinical Studies Involving Pirfenidone for Lung and Cardiac Disorders.

Study	Model	Intervention	Findings
Miric et al. 2001[72]	Rat model of STZ-induced diabetic cardiomyopathy	PFD (200 mg/day) from week 4 to week 8 after STZ treatment	PFD attenuated LV perivascular and interstitial collagen deposition and diastolic stiffness increase induced by STZ PFD did not normalise cardiac contractility
Mirkovic et al. 2002[65]	Rat model of hypertensive cardiomyopathy by single kidney removal	DOCA-salt or no further treatment for 2 weeks PFD (0.4% in powdered rat food) for further 2 weeks	PFD attenuated LV hypertrophy and reduced collagen deposition and diastolic stiffness
Giri et al. 2004[74]	DXR-induced rat model of cardiac and renal toxicity	Saline + regular diet; DXR + regular diet; saline + the same diet mixed with 0.6% PFD; DXR + the same diet mixed with 0.6% PFD for 25 days	PFD suppressed DXR-induced increases in hydroxyproline content in the heart and kidney, lipid peroxidation of the kidney and plasma and protein content of the urine PFD minimised the DXR-induced histopathological changes of heart and kidney
Lee et al. 2006[81]	Dog model of congestive heart failure	PFD (800 mg 3 times per day) for 3 weeks	PFD attenuated arrhythmogenic left atrial remodelling, left atrial fibrosis, AF duration PFD reduced TGF-β, TNF-α and metalloproteinase-9 and increased TIMP-4 levels
Van Erp et al. 2006[86]	Dystrophin-deficient mdx mouse model of Duchenne muscular dystrophy	PFD for 7 months	PFD improved cardiac contractility and decreased TGF-β expression but did not reduce extracellular matrix deposition
Yamazaki et al. 2012[67]	Mouse model of angiotensin II-induced cardiac hypertrophy	PFD (300 mg/kg/day) for 2 weeks	PFD inhibited angiotensin II-induce LV hypertrophy, decreased heart weight, attenuated mRNA expression of ANP, BNP, TGF-β1 and mineralocorticoid receptors
Wang et al. 2013[15]	Mouse model of TAC-induced LV hypertrophy	PFD (200 mg/kg) every 2 days from day 10 after surgery	PDF increased survival rate and reduced fibroblast proliferation and the expression of TGF-β1 and hydroxyproline PFD attenuated myocardial inflammation by regulating the NLRP3 inflammasome-mediated IL-1β signalling pathway
Yamagami et al. 2015[66]	Mouse model of TAC-induced LV hypertrophy	PFD (400 mg/kg) twice daily from week 4 to week 8 after surgery	PFD improved systolic function and suppressed LV dilation and fibrotic progression induced by pressure overload PFD inhibited changes in the collagen 1 and CLDN5 expression levels resulting in reduced fibrosis and vascular permeability
Andersen et al. 2019[69]	Rat model of pressure overload RV failure by pulmonary trunk banding	PFD (700 mg/kg/day) for 6 weeks	PFD did not reduce RV fibrosis or improve RV haemodynamics
Poble et al. 2019[68]	Sugen/hypoxia rat model of severe pulmonary hypertension	PFD (30 mg/kg/day) three times a day for 3 weeks	PFD reduced proliferation of pulmonary artery smooth cells and extracellular matrix deposition in lungs and RV

ANP = atrial natriuretic peptide; BNP = B-type natriuretic peptide; CLDN5 = claudin 5; DOCA = deoxycorticosterone acetate; DXR = doxorubicin; LV = left ventricle; PFD = pirfenidone; TAC = transverse aortic constriction; TGF-β = transforming growth factor-β; TNF-α = tumour necrosis factor-α; RV = right ventricle; STZ = stretpozocin.