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

Lee, Ken W.; Everett, Thomas H.; Rahmutula, Dulkon; Guerra, José M.; Wilson, Emily; Ding, Chunhua; Olgin, Jeffrey E.

doi:10.1161/circulationaha.106.624320

Cited by 206 publications

(177 citation statements)

References 48 publications

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“…14 There are a few reports concerning the effect of pirfenidone on heart diseases. Lee et al 30 investigated the effects of pirfenidone on arrhythmogenic atrial remodeling with ventricular tachypacinginduced chronic heart failure in canines. In their study, pirfenidone treatment resulted in a significant reduction of atrial fibrosis.…”

Section: Discussionmentioning

confidence: 99%

The antifibrotic agent pirfenidone inhibits angiotensin II-induced cardiac hypertrophy in mice

et al. 2011

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Pirfenidone (5-methyl-1-phenyl-2-[ 1 H]-pyridone) is an effective drug for idiopathic interstitial pneumonia that can prevent and reverse tissue fibrosis in several organs. Therefore, we investigated whether pirfenidone has a potential role in preventing angiotensin II (Ang II)-induced cardiac hypertrophy. A cardiac hypertrophic mouse model was created using an Ang II infusion (200 ng kg À1 min À1 ) in wild-type mice for 2 weeks. Mice were divided into the following three groups: a saline-infused (control) group, an Ang II infusion (vehicle) group and an Ang II infusion+pirfenidone-treated (PFD) group, which received pirfenidone (300 mg kg À1 per day) by gastric gavage during the Ang II infusion. At 2 weeks, we assessed hemodynamics and cardiac function and investigated tissue fibrosis of the myocardium histologically and genetically. Blood pressure in the vehicle group was significantly increased compared to the control group. Although blood pressure was not different between the vehicle and PFD groups, heart weight was significantly decreased in the PFD group. Echocardiography revealed that left ventricular hypertrophy was significantly increased in the vehicle group vs. the control group. Interestingly, pirfenidone significantly inhibited this effect. Continuous infusion of Ang II increased the perivascular and interstitial tissue fibrosis, and pirfenidone inhibited these fibrotic changes. Pirfenidone also inhibited Ang II-induced hypertrophy. In the vehicle group, the mRNA expressions of atrial natriuretic peptide, brain natriuretic peptide and transforming growth factor-b1 were increased, which was significantly inhibited by pirfenidone. Furthermore, the expression of mineralocorticoid receptors was attenuated by pirfenidone. These results indicate that pirfenidone might be effective as an antifibrotic drug in the treatment of cardiac hypertrophy induced by hypertension.

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Section: Discussionmentioning

confidence: 99%

The antifibrotic agent pirfenidone inhibits angiotensin II-induced cardiac hypertrophy in mice

et al. 2011

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“…17 Atrial interstitial fibrosis has been shown to increase with age in humans and has been observed in patients with AF, 18 in animal models of aging, 19 and in chronic heart failure (CHF). This atrial interstitial fibrosis has been shown to increase AF vulnerability in animal models of CHF 20 and in a transgenic mouse model for selective atrial fibrosis. 2 In our study, we directly found that the value of CVF of LAA in patients with pre-AF were higher than in patients with pre-SR.…”

Section: Ibs and Atrial Fibrosis In Patients With Preoperative Af And Srmentioning

confidence: 96%

“…Atrial fibrosis has been shown to increase AF vulnerability in animal models of heart failure and selective atrial fibrosis. 1,2 Correlative data in biopsy and autopsy specimens from patients with AF have uncovered the presence of atrial fibrosis. 3,4 Postoperative AF (post-AF) is a common problem after coronary bypass grafting (CABG).…”

Section: Introductionmentioning

confidence: 99%

Relationship Between Integrated Backscatter and Atrial Fibrosis in Patients with and Without Atrial Fibrillation Who Are Undergoing Coronary Bypass Surgery

Wang

Shen

Wang

et al. 2009

Clinical Cardiology

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Objective: The purpose of this study was to investigate the relationship between the integrated backscatter (IBS) and atrial fibrosis, with and without atrial fibrillation (AF), in patients who are undergoing coronary bypass grafting (CABG). Methods: A total of 74 patients (18 preoperative AF, 56 sinus rhythm [SR]) with coronary artery disease undergoing CABG were included. The IBS of the left atrium (LA) posterior wall was acquired from transthoracic echocardiographic examination before surgery. Samples from the LA appendage were collected after opening the pericardium and quantitative assessment of atrial fibrosis was performed with collagen volume fraction (CVF). Postoperative AF was monitored with electrocardiographic telemetry in-hospital.Results: There was a positive relationship between age, IBS of the left atrial posterior wall indexed by pericardium (IBS%), and CVF by multivariate linear regression analysis (r = 0.612, p = 0.034; r = 0.887, p<0.001 respectively). The value of IBS%, LA dimension (LAD), and CVF values were higher in patients with preoperative AF than in patients with preoperative SR (p<0.001, p<0.01, p<0.001, respectively). The value of age, IBS%, and CVF in patients with postoperative AF were higher than in patients without postoperative AF (p = 0.029, p<0.001, p = 0.001 respectively). Conclusions: IBS of the LA posterior wall indexed by pericardium provides an objective quantitative measure of atrial fibrosis and correlates with postoperative AF in patients undergoing CABG surgery.

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“…This increases heart excitability and should be considered for electrophysiological studies and evaluation of defibrillation strategies. On the contrary, dogs have very close cardiac electrophysiological properties as compared to humans [24]. Therefore, they might be an "ideal" model for arrhythmia studies but their wide use raises ethical and economical issues [25].…”

Section: Large Animal Models Of Cardiac Arrestmentioning

confidence: 99%

How Can we Study Cardiopulmonary Resuscitation and Cardiac Arrest in Animals: a Review

Blondel¹,

Kohlhauer²,

Zilberstein³

et al. 2016

JDVAR

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Animal research is essential to propose new therapeutic approaches limiting the sequels of cardiac arrest in human and veterinary medicine. The ultimate goal is to improve the long term prognosis and neurological recovery. For such investigations, the use of animal models seems unavoidable as cardiac arrest provokes multiple visceral consequences as well as inflammatory response and coagulopathy. These models allow not only a better understanding of the pathophysiology but also the investigation of new treatment strategies to improve basic life support efficiency or prevent multi-organ failure. In this review, we are summarizing the characteristics of the main animal models used in resuscitation sciences. The choice of the species and methods of evaluation of cardiac arrest is crucial. These studies often concern human medicine but they can also address fundamental questions for veterinary research as they are mostly based on animal research.

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

Cited by 206 publications

References 48 publications

The antifibrotic agent pirfenidone inhibits angiotensin II-induced cardiac hypertrophy in mice

The antifibrotic agent pirfenidone inhibits angiotensin II-induced cardiac hypertrophy in mice

Relationship Between Integrated Backscatter and Atrial Fibrosis in Patients with and Without Atrial Fibrillation Who Are Undergoing Coronary Bypass Surgery

How Can we Study Cardiopulmonary Resuscitation and Cardiac Arrest in Animals: a Review

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