Effect of Nonanticoagulant Heparin (Astenose) on Restenosis after Balloon Angioplasty in the Atherosclerotic Rabbit

Purpose: To determine whether intravenous administration of Astenose, a high-molecular-weight nonanticoagulant heparin, can reduce restenosis following balloon angioplasty in a rabbit model. Materials and Methods: Focal atherosclerosis was induced in 54 rabbits (89 vessels), and angioplasty was performed after animals were randomized into five groups. Group 1 vessels (control) were treated with lactated Ringer solution for 28 days (n = 19); group 2, Astenose at 0.10 mg/kg per hour for 28 days (n = 16); group 3, Astenose at 0.33 mg/kg per hour for 28 days (n = 16); group 4, Astenose at 0.60 mg/kg per hour for 28 days (n = 17); and group 5, Astenose at 0.33 mg/kg per hour for 14 days (n = 21). Arteriograms were obtained to measure minimal luminal diameters before, immediately after, and 28 days after angioplasty, and the rabbits were killed for histologic analysis. Results: Angiographically demonstrated restenosis was significantly reduced in groups 3 (18.9% ± 3.7, P = .04) and 4 (20.2% ± 3.1, P = .04) compared with the control group (32.4% ± 4.8). Group 5 showed a nonsignificant trend toward reduced restenosis (23.1% ± 2.9, P = .09), and group 2 showed restenosis similar to that in group 1 (31.0% ± 2.5, P = .80). However, quantitative histopathologic analysis detected no differences among the groups in absolute plaque area. Medial area was significantly smaller in groups 2 and 5 (P ≤ .002) than in group 1, and there was a nonsignificant trend toward reduced medial area in groups 3 and 4 (P = .12). Conclusion: Long-term intravenous Astenose therapy resulted in a modest but statistically significant reduction in angiographically demonstrated restenosis after angioplasty in this atherosclerotic rabbit model.