Huang Rong-chong, Yao Kang, Lu Hao, Yang Jun, Shi Hong-cheng, Zhang Yi-qi, Huang Zhe-yong, Zhang Shu-ning, Yang Shan, Sun Ai-jun, Zou Yun-zeng, Ge Jun-bo
Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Zhonghua Xin Xue Guan Bing Za Zhi. 2009 Aug;37(8):685-91.
To compare the efficacy and feasibility between intracoronary and hypodermic injection of granulocyte colony-stimulating factor (G-CSF) on improving cardiac function in a Swine model of chronic myocardial ischemia.
Eighteen Swine underwent placement of ameroid constrictor on left circumflex coronary artery. The presence of myocardial ischemia was verified at four weeks after the operation, and the animals were then randomly assigned into three groups (n = 6 each): (1) administration of vehicle (control), (2) hypodermic injection of G-CSF (5 microgxkg(-1)x;d(-1)) for five days (IH), and (3) intracoronary injection of a bonus G-CSF (60 microg/kg) (IC). Coronary angiogram, cardiac MRI, and (18)F-FDG-SPECT/(99m)Tc-SPECT (DISA-SPECT) measurements were performed at pre-administration and at 4 weeks post administration. Global heart function such as left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVSDV) and left ventricular ejection fraction (LVEF), myocardial perfusion, myocardial viability and myocardial infarct area were evaluated. Myocardial vWF, Bcl-2 and Bax expressions were detected by Western blot and RT-PCR.
MRI data showed that left ventricular dilation and dysfunction were similarly prevented in IH and IC G-CSF treated animals at eight weeks after the operation. SPECT revealed that both IH and IC G-CSF equally improved the regional contractility of chronic myocardial ischemia and increased myocardial viability. Myocardial infarct size was also reduced after both G-CSF treatments as detected by MRI. Intracoronary injection of G-CSF did not lead to angiogenesis in other organs. G-CSF treatments were also associated with a significant reduction in myocardial apoptosis and significant increase in angiogenesis.
Both intracoronary and hypodermic injection of G-CSF were safe and feasible and could equally improve cardiac function and increase angiogenesis in this Swine model of chronic myocardial ischemia.
在慢性心肌缺血猪模型中，比较冠状动脉内注射与皮下注射粒细胞集落刺激因子（G-CSF）改善心脏功能的疗效和可行性。
18只猪在左旋冠状动脉上放置阿霉素缩窄环。术后4周证实存在心肌缺血，然后将动物随机分为三组（每组n = 6）：（1）给予赋形剂（对照组），（2）皮下注射G-CSF（5μg·kg⁻¹·d⁻¹），持续5天（IH组），（3）冠状动脉内注射一次G-CSF（60μg/kg）（IC组）。在给药前和给药后4周进行冠状动脉造影、心脏磁共振成像以及（18）F-FDG-SPECT/（99m）Tc-SPECT（DISA-SPECT）测量。评估整体心脏功能，如左心室舒张末期容积（LVEDV）、左心室收缩末期容积（LVSDV）和左心室射血分数（LVEF）、心肌灌注、心肌存活能力和心肌梗死面积。通过蛋白质免疫印迹法和逆转录-聚合酶链反应检测心肌血管性血友病因子（vWF）、Bcl-2和Bax的表达。
磁共振成像数据显示，术后8周，IH组和IC组接受G-CSF治疗的动物中，左心室扩张和功能障碍得到了相似程度的预防。单光子发射计算机断层扫描显示，IH组和IC组的G-CSF均同样改善了慢性心肌缺血区域的收缩力并提高了心肌存活能力。磁共振成像检测发现，两种G-CSF治疗后心肌梗死面积也均减小。冠状动脉内注射G-CSF未导致其他器官发生血管生成。G-CSF治疗还与心肌细胞凋亡显著减少和血管生成显著增加相关。
在这个慢性心肌缺血猪模型中，冠状动脉内注射和皮下注射G-CSF均安全可行，且均可同样改善心脏功能并增加血管生成。
