Pu L Q, Gadowski G R, Graham A M, Ricci M A, Brassard R, Sniderman A D, Symes J F
Department of Surgery, Royal Victoria Hospital Montreal, Quebec, Canada.
Eur J Vasc Endovasc Surg. 1995 Feb;9(2):189-96. doi: 10.1016/s1078-5884(05)80089-9.
We previously demonstrated stimulation of collateral vessel formation in a rabbit model of unilateral limb ischaemia after administration of endothelial cell growth factor (ECGF). To distinguish clearly the effects of ischaemia alone from those of ischaemia combined with angiogenic stimulation in the same animal, a model of bilateral hindlimb ischaemia was used to evaluate further the angiogenic effect of ECGF.
Ischaemia was produced in both hindlimbs of 11 rabbits by femoral artery excision. Beginning 10 days later, ECGF (8 mg in 3 ml of saline) was injected in one hindlimb while 3 ml of saline alone was injected in the other every other day for a total of five doses.
Calf systolic blood pressure was measured in both limbs on postoperative days, 10, 30, and 50. On day 50, collateral formation was quantitated angiographically, and muscle samples were obtained for quantitation of capillary density and histologic studies.
The mean calf systolic blood pressure in the both hindlimbs was similar on day 10 (36.9 +/- 2.3 versus 38.1 +/- 2.9 mmHg) but was significantly higher in the ECGF-treated limb on day 30 (68.9 +/- 3.1 versus 45.0 +/- 2.9 mmHg) and day 50 (83.0 +/- 3.0 versus 57.0 +/- 1.7; p < 0.0001 for both comparisons). On day 50, collateral vessels were significantly more numerous in the ECGF-treated limb (17.2 +/- 1.6 versus 11.0 +/- 0.8; p < 0.0006), as were capillaries (225.9 +/- 11.4 versus 159.6 +/- 12.9 per mm2; p < 0.002).
Local administration of ECGF enhanced collateral development leading to significantly improved perfusion in the treated as compared with the untreated limb in the same animal. Exogenous administration of an angiogenic mitogen can upregulate the normal collateral response to ischaemia and may be useful in treating severe limb ischaemia.
我们先前已证明，在给予内皮细胞生长因子（ECGF）后，单侧肢体缺血的兔模型中侧支血管形成受到刺激。为了在同一动物中清楚地区分单纯缺血的影响与缺血合并血管生成刺激的影响，使用双侧后肢缺血模型进一步评估ECGF的血管生成作用。
通过切除股动脉，在11只兔子的双后肢制造缺血。10天后开始，在一侧后肢注射ECGF（8毫克溶于3毫升盐水中），而另一侧每隔一天仅注射3毫升盐水，共注射五剂。
在术后第10、30和50天测量双下肢的小腿收缩压。在第50天，通过血管造影对侧支形成进行定量，并获取肌肉样本以定量毛细血管密度并进行组织学研究。
在第10天，双后肢的平均小腿收缩压相似（36.9±2.3对38.1±2.9 mmHg），但在第30天，接受ECGF治疗的肢体明显更高（68.9±3.1对45.0±2.9 mmHg），在第50天也是如此（83.0±3.0对57.0±1.7；两次比较p均<0.0001）。在第50天，接受ECGF治疗的肢体中的侧支血管明显更多（17.2±1.6对11.0±0.8；p<0.0006），毛细血管也是如此（每平方毫米225.9±11.4对159.6±12.9；p<0.002）。
与同一动物中未治疗的肢体相比，局部给予ECGF可增强侧支发育，导致治疗肢体的灌注显著改善。外源性给予血管生成有丝分裂原可上调对缺血的正常侧支反应，可能对治疗严重肢体缺血有用。
