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

Abstract

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 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.