The Effect of Long-term Amiodarone Administration on Myocardial Fibrosis and Evolution of Left Ventricular Remodeling in a Porcine Model of Ischemic Cardiomyopathy

Overview

Journal Springerplus

Date 2016 Sep 22

PMID 27652141

Citations 5

Authors

Anastasia Zagorianou

Meletios Marougkas

Stavros G Drakos

Nikolaos Diakos

Panagiotis Konstantopoulos

Despina N Perrea

Maria Anastasiou-Nana

Konstantinos Malliaras

Affiliations

Soon will be listed here.

Abstract

Amiodarone is effective in suppressing arrhythmias in heart failure patients. We investigated the effect of long-term amiodarone administration on myocardial fibrosis and left ventricular (LV) remodeling in a porcine model of ischemic cardiomyopathy. Eighteen infarcted farm pigs were randomized to receive long-term amiodarone administration for 3 months (n = 9) or conventional follow-up (n = 9). Evolution of LV remodeling over 3 months post-myocardial infarction was examined at tissue level (myocyte size, myocardial fibrosis and vascular density assessed by whole-field digital histopathology), organ level (LV structure and function assessed by echocardiography), and systemic level (BNP and MMP-9 levels). Long-term administration of the standard anti-arrhythmic doses of amiodarone was not associated with adverse effects on myocardial fibrosis and other features of adverse cardiac remodeling. This favorable safety profile suggests that long-term anti-arrhythmic therapy with amiodarone warrants further clinical investigation in the subpopulation of heart failure patients with significantly increased burden of arrhythmias.

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References

Massie B, Fisher S, Radford M, Deedwania P, Singh B, FLETCHER R . Effect of amiodarone on clinical status and left ventricular function in patients with congestive heart failure. CHF-STAT Investigators. Circulation. 1996; 93(12):2128-34. DOI: 10.1161/01.cir.93.12.2128. View

Schwaiblmair M, Berghaus T, Haeckel T, Wagner T, von Scheidt W . Amiodarone-induced pulmonary toxicity: an under-recognized and severe adverse effect?. Clin Res Cardiol. 2010; 99(11):693-700. DOI: 10.1007/s00392-010-0181-3. View

Cleland J, Dargie H, Findlay I, Wilson J . Clinical, haemodynamic, and antiarrhythmic effects of long term treatment with amiodarone of patients in heart failure. Br Heart J. 1987; 57(5):436-45. PMC: 1277198. DOI: 10.1136/hrt.57.5.436. View

Hirasawa Y, Nakagomi A, Kobayashi Y, Katoh T, Mizuno K . Short-term amiodarone treatment attenuates the production of monocyte cytokines and chemokines by C-reactive protein and improves cardiac function in patients with idiopathic dilated cardiomyopathy and ventricular tachycardia. Circ J. 2009; 73(4):639-46. DOI: 10.1253/circj.cj-08-0794. View

Jackevicius C, Tom A, Essebag V, Eisenberg M, Rahme E, Tu J . Population-level incidence and risk factors for pulmonary toxicity associated with amiodarone. Am J Cardiol. 2011; 108(5):705-10. DOI: 10.1016/j.amjcard.2011.04.024. View

Hu K, Gaudron P, Ertl G . Effects of high- and low-dose amiodarone on mortality, left ventricular remodeling, and hemodynamics in rats with experimental myocardial infarction. J Cardiovasc Pharmacol. 2004; 44(6):627-30. DOI: 10.1097/00005344-200412000-00001. View

Bardy G, Lee K, Mark D, Poole J, Packer D, Boineau R . Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure. N Engl J Med. 2005; 352(3):225-37. DOI: 10.1056/NEJMoa043399. View

Drakos S, Kfoury A, Hammond E, Reid B, Revelo M, Rasmusson B . Impact of mechanical unloading on microvasculature and associated central remodeling features of the failing human heart. J Am Coll Cardiol. 2010; 56(5):382-91. PMC: 3052413. DOI: 10.1016/j.jacc.2010.04.019. View

Chatelain P, Meysmans L, Matteazzi J, Beaufort P, Clinet M . Interaction of the antiarrhythmic agents SR 33589 and amiodarone with the beta-adrenoceptor and adenylate cyclase in rat heart. Br J Pharmacol. 1995; 116(3):1949-56. PMC: 1908949. DOI: 10.1111/j.1476-5381.1995.tb16397.x. View

10.

Djandjighian L, Planchenault J, Finance O, Pastor G, Gautier P, Nisato D . Hemodynamic and antiadrenergic effects of dronedarone and amiodarone in animals with a healed myocardial infarction. J Cardiovasc Pharmacol. 2000; 36(3):376-83. DOI: 10.1097/00005344-200009000-00014. View

11.

Polster P, BROEKHUYSEN J . The adrenergic antagonism of amiodarone. Biochem Pharmacol. 1976; 25(2):131-4. DOI: 10.1016/0006-2952(76)90279-3. View

12.

Tachikawa H, Kodama M, Watanabe K, Takahashi T, Ma M, Kashimura T . Amiodarone improves cardiac sympathetic nerve function to hold norepinephrine in the heart, prevents left ventricular remodeling, and improves cardiac function in rat dilated cardiomyopathy. Circulation. 2005; 111(7):894-9. DOI: 10.1161/01.CIR.0000155610.49706.D2. View

13.

Nokin P, Clinet M, Schoenfeld P . Cardiac beta-adrenoceptor modulation by amiodarone. Biochem Pharmacol. 1983; 32(17):2473-7. DOI: 10.1016/0006-2952(83)90004-7. View

14.

Pfeffer M, Braunwald E . Ventricular remodeling after myocardial infarction. Experimental observations and clinical implications. Circulation. 1990; 81(4):1161-72. DOI: 10.1161/01.cir.81.4.1161. View

15.

Dixon J, Spinale F . Myocardial remodeling: cellular and extracellular events and targets. Annu Rev Physiol. 2011; 73:47-68. PMC: 3157311. DOI: 10.1146/annurev-physiol-012110-142230. View

16.

Fertin M, Dubois E, Belliard A, Amouyel P, Pinet F, Bauters C . Usefulness of circulating biomarkers for the prediction of left ventricular remodeling after myocardial infarction. Am J Cardiol. 2012; 110(2):277-83. DOI: 10.1016/j.amjcard.2012.02.069. View

17.

Papiris S, Triantafillidou C, Kolilekas L, Markoulaki D, Manali E . Amiodarone: review of pulmonary effects and toxicity. Drug Saf. 2010; 33(7):539-58. DOI: 10.2165/11532320-000000000-00000. View