Cardioprotective effect of dexrazoxane in a rat model of myocardial infarction: anti-apoptosis and promoting angiogenesis.
OBJECTIVE
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 125 mg/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.
Zhou
Ligang
L
Department of Cardiology, Children's Hospital of Chongqing Medical University, Chongqing, PR China.
Sung
Rita Yn Tz
RY
Li
Karen
K
Pong
Nga Hin
NH
Xiang
Ping
P
Shen
Jie
J
Ng
Pak Cheung
PC
Chen
Yuan
Y
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001772:Blood Cell Count; D001854:Bone Marrow Cells / Q000166:cytology; D002196:Capillaries / Q000502:physiology; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004195:Disease Models, Animal; D015536:Down-Regulation; D004452:Echocardiography; D042783:Endothelial Cells / Q000378:metabolism; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology*; D009206:Myocardium / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011929:Razoxane / Q000494:pharmacology*; D013234:Stem Cells / Q000378:metabolism; D013318:Stroke Volume; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D002316:Cardiotonic Agents; D051028:bcl-2-Associated X Protein; D011929:Razoxane