Outcomes and Risks of G-CSF Administration for CAD

冠状动脉疾病（CAD）患者经历致残性心绞痛，尽管尝试血运重建术的频率越来越高。我们假设骨髓干细胞和祖细胞的细胞因子动员可能促进心肌新生血管，缓解缺血和改善症状。我们给16例有症状的诱导性缺血患者服用10微克/公斤/天的粒细胞集落刺激因子（G-CSF），持续5天，尽管之前曾尝试过血运重建。G-CSF使CD34+/CD133+细胞从1.5 ~ 0.2 /微升增加到52.4 ~ 10.4/微升（P<0.001），表明具有内皮祖细胞潜能的细胞被动员。治疗前后血小板和凝血活性指标无明显变化，但c反应蛋白（CRP）由4.5 ~ 1.3 mg/L升高至8.6 ~ 1.3 mg/L （P=0.017）。2例患者出现严重不良事件：1)非st段抬高型心肌梗死（MI）在第5次G-CSF剂量后8小时，2)心肌梗死并在治疗后17天死亡。在治疗后1个月，多巴酚丁胺应激期间，mri确定的复合壁运动评分（从25.7 - 2.1到28.3 - 1.9，P=0.20）与基线值相比没有改善（即减少），并且缺血段数有增加的趋势（从4.5 - 0.6到6.1 - 1.0，P=0.068）。与基线测量值（11.9 ~ 0.9分钟）相比，1个月时的跑步机运动时间（改良布鲁斯方案）（12.2 ~ 0.7分钟，P=0.37）和3个月时的12例患者（11.4 ~ 0.9分钟，P=0.98）没有改善。

Patients with coronary artery disease (CAD) who experience disabling angina despite attempts at revascularization are encountered with increasing frequency. We hypothesized that cytokine mobilization of stem and progenitor cells from bone marrow may promote myocardial neovascularization with relief of ischemia and improvement in symptoms. We administered granulocyte colony-stimulating factor (G-CSF) 10 microg/kg/day for 5 days to 16 symptomatic patients with inducible ischemia despite prior attempts at revascularization. G-CSF increased CD34+/CD133+ cells from 1.5?0.2 to 52.4?10.4/microL (P<0.001), indicating mobilization of cells with endothelial progenitor potential. Indices of platelet and coagulation activation were not changed by treatment, but C-reactive protein (CRP) increased from 4.5?1.3 to 8.6?1.3 mg/L (P=0.017). Two patients experienced serious adverse events: 1) non-ST elevation myocardial infarction (MI) 8 hours after the fifth G-CSF dose, and 2) MI and death 17 days after treatment. At 1 month post-treatment, there was no improvement from baseline values (i.e., reduction) in the MRI-determined composite wall motion score (from 25.7?2.1 to 28.3?1.9, P=0.20) and a trend towards a greater number of ischemic segments (from 4.5?0.6 to 6.1?1.0, P=0.068) during dobutamine stress. There was no improvement in treadmill exercise duration (modified Bruce protocol) at 1 month (12.2?0.7 min, P=0.37), and in 12 patients at 3 months (11.4?0.9 min, P=0.98), compared with baseline measurements (11.9?0.9 min). Conclusions- G-CSF administration to CAD patients mobilizes progenitor cells from bone marrow, but without objective evidence of cardiac benefit. Significant increases in CRP may destabilize plaques and contribute to adverse outcomes during treatment in some patients.