治疗性血管生成作为重症肢体缺血患者的一种新治疗方法的安全性和有效性。

Safety and efficacy of therapeutic angiogenesis as a novel treatment in patients with critical limb ischemia.

作者信息

Lara-Hernandez R, Lozano-Vilardell P, Blanes P, Torreguitart-Mirada N, Galmés A, Besalduch J

机构信息

Vascular Surgery Department, Hospital Universitario Son Dureta, Palma de Mallorca, Baleares, Spain.

出版信息

Ann Vasc Surg. 2010 Feb;24(2):287-94. doi: 10.1016/j.avsg.2009.10.012.

DOI:10.1016/j.avsg.2009.10.012

PMID:20142004

Abstract

BACKGROUND

In some patients with critical limb ischemia (CLI) the possibility of revascularizing treatment does not exist. In this case therapeutic angiogenesis (TA) using autologous endothelial progenitor cell (EPC) transplantation could be an alternative. The objective of our study was to evaluate the safety and efficacy of TA using EPC.

METHODS

Twenty-eight patients with CLI who were not candidates for surgical or endovascular revascularization were included in a prospective study. To mobilize EPCs from the bone marrow, granulocyte colony-stimulating growth factor was injected subcutaneously at doses of 5 microg/kg/day for 5 days. Apheresis was performed, obtaining 50 mL of blood with a high rate of EPCs (CD34(+) and CD133(+) cells were counted). EPCs were implanted in the ischemic limb by intramuscular injections. Primary end points were the safety and feasibility of the procedure and limb salvage rate for amputation at 12 months. Other variables studied were improvement in rest pain, healing of ulcers, ankle-brachial pressure index (ABI), and digital plethysmography. All procedures were done pretreatment and every 3 months for a year on average. Postransplantation arteriography was done in selected cases.

RESULTS

No adverse effects were observed. Mean follow-up was 14 months. Before treatment, mean basal ABI was 0.35+/-0.2 and at 18 months postimplantation, 0.72+/-0.51 (p=0.009). There was a mean decrease of five points in pain scale: basal 8.7+/-1, after TA 3.8+/-2.9 (p=0.01). Seven patients required major amputation. Kaplan-Meier analysis revealed a limb salvage rate of 74.4% after 1 year.

CONCLUSION

Implantation of EPCs in CLI is a safe alternative, improves tissue perfusion, and obtains high amputation-free rates. Nevertheless, this is a small cohort and results should be tested with long randomized trials.

摘要

背景

在一些严重肢体缺血（CLI）患者中，不存在血管重建治疗的可能性。在这种情况下，使用自体内皮祖细胞（EPC）移植的治疗性血管生成（TA）可能是一种替代方法。我们研究的目的是评估使用EPC进行TA的安全性和有效性。

方法

28例不适合手术或血管内血管重建的CLI患者纳入一项前瞻性研究。为了从骨髓中动员EPC，以5μg/kg/天的剂量皮下注射粒细胞集落刺激生长因子，共5天。进行血液成分单采，获取50mL富含EPC的血液（计数CD34(+)和CD133(+)细胞）。通过肌肉注射将EPC植入缺血肢体。主要终点是该手术的安全性和可行性以及12个月时的肢体挽救率（避免截肢）。研究的其他变量包括静息痛的改善、溃疡愈合、踝臂压力指数（ABI）和数字体积描记法。所有检查均在治疗前以及平均为期一年的时间里每3个月进行一次。在选定的病例中进行移植后动脉造影。

结果

未观察到不良反应。平均随访14个月。治疗前，平均基础ABI为0.35±0.2，植入后18个月为0.72±0.51（p=0.009）。疼痛评分平均下降了5分：基础值为8.7±1，TA后为3.8±2.9（p=0.01）。7例患者需要进行大截肢。Kaplan-Meier分析显示1年后肢体挽救率为74.4%。