Liddell Robert P, Patel Tarak H, Weiss Clifford R, Lee David S, Matsuhashi Toshio, Brown P Rand, Gabrielson Kathleen L, Rodriguez E Rene, Eng John, Kimura Hideo, Hofmann Lawrence V
Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21287, USA.
J Vasc Interv Radiol. 2005 Jul;16(7):991-8. doi: 10.1097/01.RVI.0000161381.48445.48.
Current animal hindlimb ischemia models involve surgical ligation of the femoral artery and delivery of therapeutic angiogenic agents into the adductor compartment. The authors hypothesize that an endovascular model of hindlimb ischemia would be a more appropriate platform, closely resembling atherosclerosis by occluding the vessel from within, causing less inflammation, wound healing and subsequent collateralization.
The left superficial femoral artery in 17 rabbits was occluded by endovascular coil embolization (n=9) or surgical ligation (n=8). Animals (n=3; in each group) were sacrificed on day 3 to determine the arteriolar luminal area, number of arterioles, microsphere determined perfusion, and degree of inflammation. On day 28, the remaining animals underwent calf blood pressure measurements and angiography to determine the number of collaterals and diameter of vessels supplying the hindlimb.
Immediate postprocedure (day 0) and presacrifice (day 3 or 28) occlusion rates were 89% (eight of nine rabbits) and 100% for the endovascular model; 100% and 100% for the surgical model, respectively. Hindlimb paralysis and muscle atrophy was found in one surgical animal. On day 3, there was an increase in hindlimb perfusion (surgery, 0.04+/-0.01; endovascular, 0.02+/-0.01; P=.02), an increase in arteriolar luminal area (surgery, 481 microm+/-240; endovascular, 345 microm+/-151; P=.04), and a trend toward more inflammation (surgery, 5.5+/-3.8; endovascular, 2.5+/-3.0; P=.08) in the surgical group. There was no difference in number of vessels between both groups. On day 28 there was no difference in the calf blood pressure ratios or in the number of collaterals. However, there was enlargement of the distal profunda femoris artery, the vessel closest to the surgical incision, in the surgical group (L/R ratio: immediate post-occlusion, 1.06+/-0.11; day 28, 1.27+/-0.08; P=.02).
The endovascular model was efficacious in providing occlusion of the superficial femoral artery, and induced less of an arteriogenic response compared with the surgical model. The authors believe that this endovascular model is a superior platform for studying therapeutic angiogenic agents.
当前的动物后肢缺血模型涉及股动脉的手术结扎以及将治疗性血管生成剂注入内收肌间隙。作者推测，后肢缺血的血管内模型将是一个更合适的平台，通过从血管内部进行闭塞，更类似于动脉粥样硬化，引起的炎症、伤口愈合及随后的侧支循环形成较少。
对17只兔子的左股浅动脉进行血管内弹簧圈栓塞（n = 9）或手术结扎（n = 8）。在第3天处死动物（每组n = 3只），以确定小动脉管腔面积、小动脉数量、微球测定的灌注以及炎症程度。在第28天，对其余动物进行小腿血压测量和血管造影，以确定供应后肢的侧支数量和血管直径。
血管内模型术后即刻（第0天）和处死前（第3天或第28天）的闭塞率分别为89%（9只兔子中的8只）和100%；手术模型分别为100%和100%。在一只手术动物中发现后肢麻痹和肌肉萎缩。在第3天，手术组后肢灌注增加（手术组，0.04±0.01；血管内组，0.02±0.01；P = 0.02），小动脉管腔面积增加（手术组，481μm±240；血管内组，345μm±151；P = 0.04），并且手术组有炎症增加的趋势（手术组，5.5±3.8；血管内组，2.5±3.0；P = 0.08）。两组之间血管血管组间血管数量无差异。在第28天，小腿血压比值或侧支数量无差异。然而，手术组中最靠近手术切口的股深动脉远端有增粗（左/右比值：闭塞后即刻，1.06±0.11；第28天，1.27±0.08；P = 0.02）。
血管内模型在提供股浅动脉闭塞方面有效，并且与手术模型相比，诱导的动脉生成反应较少。作者认为这种血管内模型是研究治疗性血管生成剂的优越平台。
