Outcomes and risks of granulocyte colony-stimulating factor in patients with coronary artery disease
Outcomes and risks of granulocyte colony-stimulating factor in patients with coronary artery disease
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DOI：
10.1016/j.jacc.2005.01.067
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发表时间：
2005-11-01
影响因子：
24
通讯作者：
Cannon, RO
中科院分区：
文献类型：
--
作者：
Hill, JM;Syed, MA;Cannon, RO
目的 骨髓祖细胞的细胞因子动员可促进心肌新生血管形成，缓解缺血。 背景 冠状动脉疾病 (CAD) 患者的内皮祖细胞数量低于健康受试者。 方法 粒细胞集落刺激因子 (G-CSF) 10 μg/kg/天，持续 5 天，给 16 名 CAD 患者给药。通过流式细胞术测量祖细胞；通过运动负荷试验和多巴酚丁胺负荷心脏磁共振成像评估缺血情况。 结果 粒细胞集落刺激因子将循环中的 CD34+/CD133+ 细胞从 1.5 +/- 0.2 μl 增加到 52.4 +/- 10.4 μl (p < 0.001)，与 15 名健康受试者中观察到的反应相似 (75.1 +/- 12.6 μl，p = 0.173）。血小板和凝血激活指数未因治疗而改变，但 C 反应蛋白从 4.5 +/- 1.3 mg/l 增加至 8.6 +/- 1.3 mg/l (p = 0.017)。两名患者经历了严重的不良事件：1) 第五次 G-CSF 剂量后 8 小时发生非 ST 段抬高型心肌梗死 (MI)，2) 治疗后 17 天发生 MI 和死亡。治疗后 1 个月，室壁运动评分（从 25.7 +/- 2.1 到 28.3 +/- 1.9，p = 0.196）或灌注异常节段（从 7.6 +/- 1.1 到 7.7 +/- 1.1，p = 0.916）较基线值没有改善（即降低），并且缺血节段数量有增加的趋势（从 4.5 +/- 0.6 至 6.1 +/- 1.0，p = 0.068）。与基线相比，1 个月 (p = 0.37) 或 3 个月 (p = 0.98) 的运动持续时间没有改善。 结论 CAD 患者给予粒细胞集落刺激因子可动员骨髓中具有内皮祖细胞潜力的细胞，但没有心脏益处的客观证据，并且在某些患者中可能出现不良后果。
OBJECTIVES Cytokine mobilization of progenitor cells from bone marrow may promote myocardial neovascularization with relief of ischemia.BACKGROUND Patients with coronary artery disease (CAD) have low numbers of endothelial progenitor cells compared with healthy subjects.METHODS Granulocyte colony-stimulating factor (G-CSF), 10 mu g/kg/day for five days, was administered to 16 CAD patients. Progenitor cells were measured by flow cytometry; ischemia was assessed by exercise stress testing and by dobutamine stress cardiac magnetic resonance imaging.RESULTS Granulocyte colony-stimulating factor increased CD34+/CD133+ cells in the circulation from 1.5 +/- 0.2 mu l to 52.4 +/- 10.4 mu l (p < 0.001), similar to the response observed in 15 healthy subjects (75.1 +/- 12.6 mu l, p = 0.173). Indices of platelet and coagulation activation were not changed by treatment, but C-reactive protein increased from 4.5 +/- 1.3 mg/l to 8.6 +/- 1.3 mg/l (p = 0.017). Two patients experienced serious adverse events: 1) non-ST-segment elevation myocardial infarction (MI) 8 h after the fifth G-CSF dose, and 2) MI and death 17 days after treatment. At 1 month after treatment, there was no improvement from baseline values (i.e., reduction) in wall motion score (from 25.7 +/- 2.1 to 28.3 +/- 1.9, p = 0.196) or segments with abnormal perfusion (7.6 +/- 1.1 to 7.7 +/- 1.1, p = 0.916) and a trend towards a greater number of ischemic segments (from 4.5 +/- 0.6 to 6.1 +/- 1.0, p = 0.068). There was no improvement in exercise duration at 1 month (p = 0.37) or at 3 months (p = 0.98) versus baseline.CONCLUSIONS Granulocyte colony-stimulating factor administration to CAD patients mobilizes cells with endothelial progenitor potential from bone marrow, but without objective evidence of cardiac benefit and with the potential for adverse outcomes in some patients.