Comparative trial of local pharmacotherapy with L-arginine, r-hirudin, andmolsidomine to reduce restenosis after balloon angioplasty of stenotic rabbit iliac arteries

PURPOSE:fo determine if local application of L-arginine, r-hirudin, or mols idomine significantly reduces restenosis after balloon angioplasty in steno tic rabbit iliac arteries. MATERIALS AND METHODS: Thirty-one male cholesterol-fed New Zealand white ra bbits underwent balloon dilation of both common iliac arteries to induce ar terial stenosis. Four weeks later, one stenotic iliac artery was simultaneo usly dilated and received local application of L-arginine (210 mg/mL, n = 7 ), r-hirudin (0.5 mg/mL, n = 8), or molsidomine (0.2 mg/mL, n = 8) with a c hanneled balloon catheter. On the contralateral side, 0.9% saline was injec ted as a control. In eight sham animals, saline was applied to one iliac ar tery and balloon dilation to only the contralateral artery. Six weeks after local treatment, vessels were harvested, and computerized morphometric and immunohistologic analyses were performed. RESULTS: Application of drugs resulted in a significant reduction of neoint imal area as follows: 53% with L-arginine (1.01 mm(2) vs 2.17 mm(2), P < .0 5), 43% with molsidomine (1.04 mm(2) vs 1.89 mm(2), p < .05), and 20% with r-hirudin (1.79 mm(2) vs 2.24 mm(2), P < .05). infusion of saline led to a significant increase (50%, 1.21 mm(2) vs 1.93 mm(2), P < .05) in neointimal area compared with balloon dilation alone. Immunohistologic findings showe d a significant reduction of macrophages (5.0% vs 10.2%, P < .05) and proli ferating cells (6.2% vs 10.6%, P < .05) in the neointima after local applic ation of L-arginine. CONCLUSION: Reduction of neointimal area was significant for L-arginine and molsidomine but not for r-hirudin. Saline infusion caused significant arte rial trauma, resulting in additional neointimal proliferation.