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 vessel), 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 < or = .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.