Scheinowitz M, Shou M, Banai S, Gertz S D, Lazarous D F, Unger E F
Experimental Physiology and Pharmacology Section, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland.
Lab Invest. 1994 Dec;71(6):813-9.
A number of experimental preparations have been used to elucidate the pathophysiology of restenosis after percutaneous transluminal coronary angioplasty; however, few models have been advanced that address restenosis in coronary arteries, and none provides an effective means of continuous local drug delivery. In this report, we describe a model of restenosis in coronary arteries with the provision for local, continuous delivery of cytotoxic and/or anti-proliferative agents.
An ameroid constrictor was placed on the left circumflex coronary artery of 17 normocholesterolemic dogs. One month later, after substantial collateral development had ensued, a segment of the left circumflex coronary artery distal to the ameroid was mechanically compressed using surgical forceps for 10 (N = 4), 15 (N = 4), 20 (N = 2), or 30 minutes (N = 5). In two dogs, an indwelling left circumflex catheter and implanted pump maintained a continuous infusion of saline at the injury site. In addition, the pump side port provided transcutaneous access for serial, selective coronary arteriography. The animals were maintained on a normal diet, without cholesterol or fat supplementation.
Three weeks after vascular injury, significant neointimal proliferation was observed in all dogs that was morphologically similar to the proliferation seen after percutaneous transluminal coronary angioplasty in human coronary arteries. The extent of neointimal formation was linearly related to the duration of injury: neointimal/medial area ratios were 0.35 +/- 0.10, 0.46 +/- 0.10, 0.58 +/- 0.03, and 1.16 +/- 0.26 (mean +/- SE) after 10, 15, 20, and 30 minutes of mechanical compression injury, respectively.
This model produces striking neointimal proliferation in the coronary arteries of normocholesterolemic dogs, morphologically similar to that seen in human coronary restenosis specimens. The model appears suitable to test the efficacy of agents with the potential to inhibit neointimal formation, providing continuous intracoronary drug delivery, as well as transcutaneous access for serial, selective arteriography.
已经使用了多种实验制剂来阐明经皮腔内冠状动脉成形术后再狭窄的病理生理学；然而，很少有模型涉及冠状动脉再狭窄，并且没有一个模型提供连续局部给药的有效方法。在本报告中，我们描述了一种冠状动脉再狭窄模型，该模型可局部、持续递送细胞毒性和/或抗增殖剂。
将一个阿梅里德缩窄器置于17只血脂正常的犬的左旋冠状动脉上。一个月后，在大量侧支循环形成后，使用手术钳对阿梅里德远端的左旋冠状动脉节段进行机械压迫10（n = 4）、15（n = 4）、20（n = 2）或30分钟（n = 5）。在两只犬中，一根留置的左旋冠状动脉导管和植入的泵在损伤部位持续输注生理盐水。此外，泵的侧端口提供经皮通路用于系列选择性冠状动脉造影。动物维持正常饮食，不补充胆固醇或脂肪。
血管损伤后三周，在所有犬中均观察到显著的新生内膜增生，其形态与人类冠状动脉经皮腔内冠状动脉成形术后所见的增生相似。新生内膜形成的程度与损伤持续时间呈线性相关：在机械压迫损伤10、15、20和30分钟后，新生内膜/中膜面积比分别为0.35±0.10、0.46±0.10、0.58±0.03和1.16±0.26（平均值±标准误）。
该模型在血脂正常的犬冠状动脉中产生显著的新生内膜增生，形态与人类冠状动脉再狭窄标本中所见相似。该模型似乎适合测试具有抑制新生内膜形成潜力的药物的疗效，提供冠状动脉内持续给药以及经皮通路用于系列选择性动脉造影。
