Barry W L, Wiegman P J, Gimple L W, Gertz S D, Powers E R, Owens G K, Sarembock I J
Department of Medicine, University of Virginia, Charlottesville, USA.
Lab Invest. 1997 Jul;77(1):109-16.
Air desiccation endothelial injury followed by cholesterol feeding is known to induce focal femoral atherosclerosis in rabbits. We previously demonstrated the effectiveness of hirudin in limiting restenosis after balloon angioplasty (BA) in this double instrumentation injury (DI) model. In the present study, we sought to determine whether BA without prior air desiccation endothelial injury (single instrumentation injury (SI)) would lead to similar femoral lesions, and whether the response to this injury might also be limited by hirudin. Accordingly, 38 femoral arteries of cholesterol-fed rabbits underwent BA with (n = 18, DI group) or without (n = 20, SI group) prior air desiccation endothelial injury. Animals were killed 24 hours or 28 days after BA. Twenty-four hours after BA, the SI group (n = 10) had a significantly smaller percentage of cross-sectional area narrowing by plaque than the DI group (n = 8) (0% versus 42% +/- 9%, p = 0.008). However, 28 days after BA, the percentages of cross-sectional area narrowing by plaque in the SI (n = 10) and DI (n = 10) groups were similar (59% +/- 6% versus 68% +/- 1%, p = NS). The percentages of intima (16% +/- 3% versus 16% +/- 3%, p = NS) and media occupied by foam cells were also similar in the two groups. To test whether hirudin administration would limit arterial narrowing after injury in the SI model, we randomly assigned cholesterol-fed rabbits that had not undergone air desiccation injury to either bolus hirudin followed by repeat dosing 24 hours after BA or bolus heparin (150 U/kg) at the time of BA. The hirudin-treated group showed significantly less angiographic and histologic restenosis 28 days after BA, despite no difference in early (0 to 72 hours) cumulative cellular proliferation between the two groups. Thus, in the cholesterol-fed rabbit, plaque formation and foam cell accumulation are similar after BA of a non-air-desiccated (SI) or focally atherosclerotic (DI) artery. Thrombin inhibition with hirudin limits arterial narrowing after SI, further emphasizing the role of thrombin in neointimal growth after injury.
已知空气干燥致内皮损伤后再给予胆固醇喂养可诱导家兔股动脉局灶性动脉粥样硬化。我们之前在这种双重器械损伤（DI）模型中证明了水蛭素在限制球囊血管成形术（BA）后再狭窄方面的有效性。在本研究中，我们试图确定无预先空气干燥致内皮损伤的BA（单一器械损伤（SI））是否会导致类似的股动脉病变，以及水蛭素是否也能限制对这种损伤的反应。因此，38只给予胆固醇喂养的家兔的股动脉接受了有（n = 18，DI组）或无（n = 20，SI组）预先空气干燥致内皮损伤的BA。在BA后24小时或28天处死动物。BA后24小时，SI组（n = 10）斑块导致的横截面积狭窄百分比显著小于DI组（n = 8）（0%对42%±9%，p = 0.008）。然而，BA后28天，SI组（n = 10）和DI组（n = 10）斑块导致的横截面积狭窄百分比相似（59%±6%对68%±1%，p = 无显著性差异）。两组中内膜（16%±3%对16%±3%，p = 无显著性差异）和被泡沫细胞占据的中膜的百分比也相似。为了测试给予水蛭素是否会限制SI模型中损伤后的动脉狭窄，我们将未接受空气干燥损伤的给予胆固醇喂养的家兔随机分为两组，一组在BA后给予单次剂量水蛭素，24小时后重复给药，另一组在BA时给予单次剂量肝素（150 U/kg）。水蛭素治疗组在BA后28天的血管造影和组织学再狭窄明显减轻，尽管两组之间早期（0至72小时）累积细胞增殖无差异。因此，在给予胆固醇喂养的家兔中，非空气干燥（SI）或局灶性动脉粥样硬化（DI）动脉BA后斑块形成和泡沫细胞积累相似。用水蛭素抑制凝血酶可限制SI后的动脉狭窄，进一步强调了凝血酶在损伤后新生内膜生长中的作用。
