Pu L Q, Sniderman A D, Brassard R, Lachapelle K J, Graham A M, Lisbona R, Symes J F
Department of Surgery, Royal Victoria Hospital, Montreal, Quebec, Canada.
Circulation. 1993 Jul;88(1):208-15. doi: 10.1161/01.cir.88.1.208.
This study tests the efficacy of an angiogenic growth factor, endothelial cell growth factor, in a rabbit model of persistent hindlimb ischemia.
Ischemia was induced in the left hindlimb of 22 New Zealand White rabbits by ligation of the distal external iliac artery and complete excision of the common and superficial femoral arteries. Two groups of animals were studied: Group 1 consisted of 11 animals who for 10 days received daily intramuscular injections of 4 mg of endothelial cell growth factor beginning on postoperative day 11, and group 2 consisted of 11 animals who underwent the same surgical ischemic procedure but received only injections of saline daily for the same postoperative period. Perfusion of the ischemic left limb was compared with the normal right limb in each animal on postoperative days 10, 20, 30, and 40 using the calf blood pressure ratio, 99mTc macroaggregate radioisotopic perfusion scans, and serial angiography. Neovascularization in the left thigh at day 40 was quantified from the angiograms. Each technique documented that animals in group 1 had significantly better perfusion than animals in group 2; that is, the calf pressure ratio was higher in group 1 than in group 2 (0.56 versus 0.32 at day 20, 0.64 versus 0.44 at day 30, and 0.70 versus 0.50, P < .0001), and the calf radioisotopic perfusion ratio was also higher in group 1 than in group 2 (0.88 versus 0.74 at day 20, P < .02; 0.93 versus 0.76 at day 30, and 0.96 versus 0.79 at day 40, P < .008). Angiographic studies correlated well with these results demonstrating much earlier distal arterial reconstitution and enhanced neovascularization (23.8 versus 9.0 vessels, P < .007).
The data clearly indicate that an angiogenic growth factor, endothelial cell growth factor, promotes revascularization in this experimental ischemic hindlimb model, raising the possibility that in the future such agents might be of value in humans.
本研究在兔持续性后肢缺血模型中测试血管生成生长因子——内皮细胞生长因子的疗效。
通过结扎髂外动脉远端并完全切除股总动脉和股浅动脉，在22只新西兰白兔的左后肢诱导缺血。研究了两组动物：第1组由11只动物组成，从术后第11天开始，连续10天每天接受4毫克内皮细胞生长因子的肌肉注射；第2组由11只动物组成，接受相同的手术缺血操作，但在相同的术后期间仅每天注射生理盐水。在术后第10、20、30和40天，使用小腿血压比值、99mTc大颗粒放射性同位素灌注扫描和系列血管造影，将每只动物缺血左肢的灌注情况与正常右肢进行比较。从血管造影照片对第40天左大腿的新生血管形成进行定量分析。每种技术均证明第1组动物的灌注明显优于第2组动物；也就是说，第1组的小腿压力比值高于第2组（第20天时分别为0.56对0.32，第30天时为0.64对0.44，第40天时为0.70对0.50，P <.0001），并且第1组的小腿放射性同位素灌注比值也高于第2组（第20天时分别为0.88对0.74，P <.02；第30天时为0.93对0.76，第40天时为0.96对0.79，P <.008）。血管造影研究与这些结果相关性良好，显示远端动脉重建明显更早且新生血管形成增强（分别为23.8条血管对9.0条血管，P <.007）。
数据清楚地表明，血管生成生长因子——内皮细胞生长因子可促进该实验性缺血后肢模型中的血管重建，这增加了未来此类药物可能对人类有价值的可能性。
