Cardioprotective effect of dexrazoxane in a rat model of myocardial infarction: Anti-apoptosis and promoting angiogenesis

Zhou, Ligang; Sung, Rita Yn Tz; Li, Karen; Pong, Nga Hin; Xiang, Ping; Shen, Jie; Ng, Pak Cheung; Chen, Yuan

doi:10.1016/j.ijcard.2010.07.015

« Previous Next »International Journal of Cardiology
Volume 152, Issue 2 , Pages 196-201, 20 October 2011

Cardioprotective effect of dexrazoxane in a rat model of myocardial infarction: Anti-apoptosis and promoting angiogenesis

Ligang Zhou
- Department of Cardiology, Children's Hospital of Chongqing Medical University, Chongqing, P.R. China
- These authors contributed equally to this manuscript.
Rita Yn Tz Sung
- Li Ka Shing Institute of Health Sciences, Department of Paediatrics, The Chinese University of Hong Kong, Hong Kong
- These authors contributed equally to this manuscript.
Karen Li
- Li Ka Shing Institute of Health Sciences, Department of Paediatrics, The Chinese University of Hong Kong, Hong Kong
- These authors contributed equally to this manuscript.
Nga Hin Pong
- Li Ka Shing Institute of Health Sciences, Department of Paediatrics, The Chinese University of Hong Kong, Hong Kong
Ping Xiang
- Department of Cardiology, Children's Hospital of Chongqing Medical University, Chongqing, P.R. China
Jie Shen
- Department of Paediatrics, Daping Hospital & Research Institute of Surgery of Third Military Medical University, Chongqing, P.R. China
Pak Cheung Ng
- Li Ka Shing Institute of Health Sciences, Department of Paediatrics, The Chinese University of Hong Kong, Hong Kong
Yuan Chen
- Department of Cardiology, Children's Hospital of Chongqing Medical University, Chongqing, P.R. China
- Corresponding author. Department of Cardiology, Children's Hospital of Chongqing Medical University, 136 Zhongshan Er Road, Yuzhong District, Chongqing, PR China. Tel.: +86 6363 1938; fax: +86 6362 2874.

Received 15 March 2010; received in revised form 18 May 2010; accepted 4 July 2010. published online 09 August 2010.

Abstract

Objectives

Dexrazoxane (DZR) is a clinically approved agent for preventive treatment of doxorubicin-induced cardiotoxicity. The objective of this study was to investigate the cardioprotective effects of DZR in a rat model of myocardial infarction (MI).

Methods

Sprague–Dawley rats were randomly divided into four groups: MI (n=16), MI+DZR (n=16), SHAM-operated (n=14) and DZR-only (n=9). MI animals were subjected to left anterior descending coronary artery ligation. DZR was administered as a single dose at 125mg/kg intraperitoneally. Four weeks after treatment, cardiac function by echocardiography, infarct size, capillary density in the infarct border zone, bone marrow-derived endothelial progenitor cells (EPCs), and cardiac expression of Bax were measured.

Results

Our results demonstrated that MI animals had compromised heart parameters. DZR treatment in MI animals resulted in reduction in infarct size (P=0.013) and improved cardiac functions in terms of fractional shortening (P=0.004) and ejection fraction (P=0.004). The capillary density (P=0.008) and bone marrow-derived EPCs (P<0.05) were higher in the MI+DZR group than those in the untreated MI group. Bax expression was down-regulated in heart tissues of MI+DZR animals (P=0.043).

Conclusions

Our study demonstrated that DZR exerted a cardioprotective effect in the rat model of MI, and the mechanism might be associated with anti-apoptosis and increased neovascularization.

Keywords: Dexrazoxane, Myocardial infarction, Cardioprotection, Endothelial progenitor cells, Bax