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Eur J Cardiothorac Surg 2008;34:661-666. doi:10.1016/j.ejcts.2008.05.035
Copyright © 2008, European Association for Cardio-thoracic Surgery. Published by Elsevier. All rights reserved.

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Low dose cyclophosphamide rescues myocardial function from ischemia-reperfusion in rats

Jianhua Zhua,b, Yuangang Qiua,b,*, Qiqi Wanga,b, Yujuan Zhua,b, Shenjiang Hua,b, Liangrong Zhenga,b, Lihong Wanga,b, Yun Zhanga,b

a Department of Cardiology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, PR China
b Institute of Cardiology, Zhejiang University, Hangzhou, PR China

Received 28 January 2008; received in revised form 15 May 2008; accepted 15 May 2008.

* Corresponding author. Address: Department of Cardiology, the First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, 310003, PR China. Tel.: +86 571 87236569; fax: +86 571 87236569. (Email: qiuyuangang1{at}yahoo.com.cn).

Objectives: The effect of low dose of cyclophosphamide (CP) protecting cardiac function from ischemia-reperfusion injury was studied on rats. The premise is that CP inhibits immune and inflammatory process, thereby limits I/R injury and improves myocardial function. Methods: Open chest rats were submitted to 30 min of ischemia followed by 3 h, 12 h or 24 h of reperfusion. Rats were divided into sham group, I/R group and CP group, and each group included 3 time-point subgroups (3 h, 12 h and 24 h; n = 8 for each subgroup). A total of 750 mg/m2 cyclophosphamide was intraperitoneally administrated in CP group and saline was given to I/R group. A polyethylene tube was inserted into the left ventricular cavity to detect left ventricular systolic pressure (LVSP) and ±dp/dt max. At the end of the experiment, hearts were harvested for histopathological assessment and infarct size determination. Results: Compared with I/R group, rats treated with low dose CP showed a significant recovery in myocardial function with improved LVSP (88 ± 11 vs 69 ± 11 mmHg of 3 h; 92 ± 11 vs 64 ± 14 mmHg of 12 h; 90 ± 11 vs 64 ± 14 mmHg of 24 h; p < 0.01 respectively). The ±dp/dt max also had the similar trends. The myocardial infarct size was reduced in CP group compared to that in I/R group; the infiltration of polymorph nuclear leukocytes (PMNs) in myocardium was decreased in CP group. The histopathological damage score was also attenuated. Conclusions: These findings suggest that low dose CP rescues cardiac function from ischemia-reperfusion injury by alleviating histopathological damage in rat myocardium.

Key Words: Ischemia • Reperfusion • Hemodynamics • Cyclophosphamide • Myocardial stunning







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Copyright © 2008 European Association for Cardio-Thoracic Surgery. Published by Elsevier. All rights reserved.