Comparative trial of local pharmacotherapy with L-arginine, r-hirudin, and molsidomine to reduce restenosis after balloon angioplasty of stenotic rabbit iliac arteries.
OBJECTIVE
To determine if local application of L-arginine, r-hirudin, or molsidomine significantly reduces restenosis after balloon angioplasty in stenotic rabbit iliac arteries.


METHODS
Thirty-one male cholesterol-fed New Zealand white rabbits underwent balloon dilation of both common iliac arteries to induce arterial stenosis. Four weeks later, one stenotic iliac artery was simultaneously 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 channeled balloon catheter. On the contralateral side, 0.9% saline was injected as a control. In eight sham animals, saline was applied to one iliac artery 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 neointimal area as follows: 53% with L-arginine (1.01 mm(2) vs. 2.17 mm(2), P <.05), 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 showed a significant reduction of macrophages (5.0% vs. 10.2%, P <.05) and proliferating cells (6.2% vs. 10.6%, P <.05) in the neointima after local application of L-arginine.


CONCLUSIONS
Reduction of neointimal area was significant for L-arginine and molsidomine but not for r-hirudin. Saline infusion caused significant arterial trauma, resulting in additional neointimal proliferation.
Kalinowski
M
M
Department of Diagnostic Radiology, Philipps-University Hospital, Marburg, Germany.
Alfke
H
H
Bergen
S
S
Klose
K J
KJ
Barry
J J
JJ
Wagner
H J
HJ
D000287:Administration, Topical; D000800:Angioplasty, Balloon; D000818:Animals; D000991:Antithrombins / Q000008:administration & dosage / Q000627:therapeutic use*; D001120:Arginine / Q000008:administration & dosage / Q000627:therapeutic use*; D003251:Constriction, Pathologic / Q000517:prevention & control; D024764:Hirudin Therapy; D006629:Hirudins / Q000008:administration & dosage; D007083:Iliac Artery; D008297:Male; D008981:Molsidomine / Q000008:administration & dosage / Q000627:therapeutic use*; D020030:Nitric Oxide Donors / Q000008:administration & dosage / Q000627:therapeutic use*; D011817:Rabbits; D012008:Recurrence; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000627:therapeutic use
D000991:Antithrombins; D006629:Hirudins; D020030:Nitric Oxide Donors; D014665:Vasodilator Agents; D001120:Arginine; D008981:Molsidomine