Protective effects of erythropoietin on cirrhotic cardiomyopathy in rats

Introduction: Erythropoietin exerts cardioprotective effects. The present study aimed to investigate the therapeutic effects of erythropoietin on cirrhotic cardiomyopathy. Materials and methods: Rats were divided into 5 groups: sham control; sham+ erythropoietin; bile duct ligation; bile duct ligation + erythropoietin; bile duct ligation + erythropoietin + anti-tumour necrosis factor alpha (TNF alpha) antibody and were studied 4 wk after surgery. Erythropoietin was administrated for 10 days before the study date. TNF alpha, erythropoietin receptor-1 expression and oxidative stress-related parameters were measured. In separate groups, isolated cardiomyocytes were subjected to contractile and relaxation studies. Cardiomyocyte cell line was used to test the direct effect of erythropoietin on nuclear factor (erythroid-derived 2)-like 2(Nrf2). Results: Erythropoietin receptor-1, TNF alpha and oxidative modified proteins were significantly increased (p<0.01), and the antioxidant regulator Nrf2 transcription decreased in cirrhotic hearts (p<0.01). Erythropoietin reversed these parameters. Maximal cardiac contractile and relaxation velocity was significantly decreased in cirrhotic cardiomyocytes. Erythropoietin significantly reversed these inhibitions. Anti-TNF alpha antibody significantly decreased cardiac TNF alpha content but did not further increase contractility. Conclusions: TNF alpha and oxidative stress are involved in cardiac dysfunction in the cirrhotic heart. Erythropoietin significantly decreased TNF alpha and oxidative stress and reversed the impaired cardiac function. (C) 2012 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.