Cyclophosphamide Protects Myocardial Ischemia-reperfusion Injury In Rats

Object:Cyclophosphamide has been used in the treatment of autoimmune disorders, including systemic vasculitis,rheumatoid arthritis et al.There is inflammation in myocardial ischemia-reperfusion injury similar to that in autoimmune disorders.We hypothesized that myocardial ischemia-reperfusion injury could be partially ameliorated with cyclophosphamide treatment by decreasing the polymorph nuclear leukocytes infiltration in myocardium and the endogenous plasma hs-CRP in rat.Methods:Open-chest rats submitted to 30min of ischemia following 3h,12h or 24h of reperfusion.All rescued 72 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 sugroup).Cyclophosphamide(0.75g/m~2)or saline was intraperitonealy administrated in CP group or I/R group.A polyethylene tube was inserted into the left ventricular cavity to detect left ventricular systolic pressure(LVSP),left ventricular end diastolic pressure(LVEDP)and±dp/dt_max.In the end,blood was collected for hs-CRP detecting,hearts were harvested for histopathological assessment and infarct size determination.Results:Compared with I/R group,hearts treated with cyclophosphamide showed a significant recovery in myocardial function with improved LVSP(88.3±3.8 vs.68.6±3.8 mmHg of 3 h;92.0±3.8 vs.63.7±4.9 mmHg of 12 h;90.4±4.0 vs.64.2±4.9 mmHg of 24 h;P＜0.01 respectively);The LVEDP and±dp/dtmax also had the similar trends;The infarct size was reduced(26.07±0.36%vs.40.35%±0.36%of 3 h;21.59±0.41%vs.49.94±0.41%of 12 h;21.62±0.42%vs.40.02±0.42%of 24 h;P＜0.01 respectively);And histopathological damage score was attenuated;The polymorph nuclear leukocytes(PMNs)infiltration in myocardium decreased in 400x high-power(HPF)fields(6.88±2.7 vs.20.38±1.5/HPF of 3 h;18.63±2.8 vs. 37.50±3.6 / HPF of 12 h,and 16.75±2.5 vs.58.75±5.0/HPF of 24 h,P＜0.01 respectively).And plasma hs-CRP concentration was significantly reduced(29.28±0.51 vs.32.26±0.51 ng/ml of 3 h;29.06±0.50 vs.31.8±0.51 ng/ml of 12 h and 28.61±0.51 vs.31.86±0.51 ng/ml of 24 h;respectively).Conclusions:Cyclophosphamide protects myocardial ischemia-reperfusion injury in rat along with attenuated PMNs infiltration and decreased serum hs-CRP.