Zhu Jianhua, Qiu Yuangang, Wang Qiqi, Zhu Yujuan, Hu Shenjiang, Zheng Liangrong, Wang Lihong, Zhang Yun
Department of Cardiology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, PR China.
Eur J Cardiothorac Surg. 2008 Sep;34(3):661-6. doi: 10.1016/j.ejcts.2008.05.035. Epub 2008 Jun 26.
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.
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.
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.
These findings suggest that low dose CP rescues cardiac function from ischemia-reperfusion injury by alleviating histopathological damage in rat myocardium.
研究低剂量环磷酰胺（CP）对大鼠心脏功能缺血再灌注损伤的保护作用。前提是CP抑制免疫和炎症过程，从而限制缺血/再灌注损伤并改善心肌功能。
开胸大鼠经历30分钟缺血，随后再灌注3小时、12小时或24小时。大鼠分为假手术组、缺血/再灌注组和CP组，每组包括3个时间点亚组（3小时、12小时和24小时；每个亚组n = 8）。CP组腹腔注射750 mg/m²环磷酰胺，缺血/再灌注组给予生理盐水。将一根聚乙烯管插入左心室腔以检测左心室收缩压（LVSP）和±dp/dt(max)。实验结束时，取出心脏进行组织病理学评估和梗死面积测定。
与缺血/再灌注组相比，低剂量CP治疗的大鼠心肌功能显著恢复，LVSP改善（3小时时88±11 vs 69±11 mmHg；12小时时92±11 vs 64±14 mmHg；24小时时90±11 vs 64±14 mmHg；p均<0.01）。±dp/dt(max)也有类似趋势。CP组心肌梗死面积比缺血/再灌注组减小；CP组心肌中多形核白细胞（PMN）浸润减少。组织病理学损伤评分也减轻。
这些发现表明低剂量CP通过减轻大鼠心肌组织病理学损伤，使心脏功能从缺血再灌注损伤中得到挽救。
