BFGF ON LOWER EXTREMITY BLOOD FLOW IN PTS WITH INTERMITTENT CLAUDICATION

临床前研究表明，碱性成纤维细胞 生长因子(BFGF)，一种血管生成多肽，促进络脉 心肌和后肢缺血模型的研究进展。我们 评价动脉内应用碱性成纤维细胞生长因子治疗慢性阻塞性肺疾病的安全性 间歇性跛行，并研究其对小腿血流的影响。 一项双盲、安慰剂对照、剂量递增试验 踝/臂收缩指数在跛行患者中的应用 &lt；0.8。患者被随机分配给安慰剂(n=6)，10微克/公斤 碱性成纤维细胞生长因子(由加州芒廷维尤Scios公司提供)(n=4)，30 碱性成纤维细胞生长因子1次(n=5)30微克/kg，2次(n=4)。 将研究药物注入缺血区的股动脉 腿。用应变仪测量小腿血流量 最后2个治疗组和4个安慰剂的体积描记 患者在治疗前、治疗后1个月和6个月。 跛行程度的主观变化通过一项 问卷调查。动脉内碱性成纤维细胞生长因子耐受性良好。碱性成纤维细胞生长因子 1个月后小牛血流量显著提高66+/-26% (平均+/-扫描电子显微镜)，6个月时为153+/-51%(n=9，P=0.002)。 患者小腿血流量增加的幅度更大。 接受2剂bFGF，而1剂为30微克/公斤。流动 在安慰剂组中没有明显变化。碱性成纤维细胞生长因子治疗 患者报告了症状的主观改善 跛行，与安慰剂患者形成对比。在患有 间歇性跛行，动脉内注射2次30微克/公斤碱性成纤维细胞生长因子 是安全的。尽管有必要进行更大规模的验证性试验，但我们的 结果提供了第一个随机化的概念证明 血管生成治疗可以的双盲、安慰剂对照试验 梗阻患者侧支循环增强的结果 外周动脉疾病。

Preclinical studies have shown that basic fibroblast growth factor (bFGF), an angiogenic peptide, promotes collateral development in models of myocardial and hind limb ischemia. We assessed the safety of intra-arterial bFGF in patients with intermittent claudication, and studied its effects on calf blood flow. A double-blind, placebo-controlled, dose-escalation trial was conducted in claudication patients with ankle/brachial systolic index <0.8. Patients were randomly assigned to placebo (n=6), 10 mcg/kg of bFGF (provided by Scios, Inc., Mountainview, CA) (n=4), 30 mcg/kg of bFGF once (n=5) and 30 mcg/kg of bFGF twice (n=4). The study drug was infused into the femoral artery of the ischemic leg. Calf blood flow was measured with strain gauge plethysmography in the final 2 treated groups and in 4 placebo patients, prior to treatment, and at 1 and 6 months after treatment. Subjective changes in the degree of claudication were assessed by a questionnaire. Intra arterial bFGF was well tolerated. bFGF significantly improved calf blood flow at 1 month by 66 +/- 26% (mean +/- SEM), and at 6 months by 153 +/- 51% (n=9, P=0.002). The magnitude of increase in calf blood flow was greater in patients receiving 2 doses of bFGF compared to 1 dose of 30 mcg/kg. Flow did not change significantly in the placebo group. bFGF-treated patients reported subjective improvement in symptoms of claudication, in contrast to placebo patients. In patients with intermittent claudication, 2 intra-arterial doses of 30 mcg/kg bFGF are safe. Although a larger confirmatory trial is necessary, our results provide the first proof of concept in a randomized double-blinded, placebo-controlled trial that angiogenic therapy can result in enhanced collateral flow in patients with obstructive peripheral arterial disease.