Low dose cyclophosphamide rescues myocardial function from ischemia-reperfusion in rats.
OBJECTIVE
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 3h, 12h or 24h of reperfusion. Rats were divided into sham group, I/R group and CP group, and each group included 3 time-point subgroups (3h, 12h and 24h; n=8 for each subgroup). A total of 750 mg/m(2) 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 3h; 92+/-11 vs 64+/-14 mmHg of 12h; 90+/-11 vs 64+/-14 mmHg of 24h; 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.
Zhu
Jianhua
J
Department of Cardiology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, PR China.
Qiu
Yuangang
Y
Wang
Qiqi
Q
Zhu
Yujuan
Y
Hu
Shenjiang
S
Zheng
Liangrong
L
Wang
Lihong
L
Zhang
Yun
Y
D000818:Animals; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D004353:Drug Evaluation, Preclinical / Q000379:methods; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology / Q000517:prevention & control; D015428:Myocardial Reperfusion Injury / Q000473:pathology / Q000517:prevention & control*; D020556:Neutrophil Infiltration / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D016277:Ventricular Function, Left / Q000187:drug effects
D007166:Immunosuppressive Agents; D003520:Cyclophosphamide