Effects of local delivery of trapidil on neointima formation in a rabbit angioplasty model.
1. Smooth muscle cell (SMC) proliferation can result in luminal reduction of a vessel following balloon angioplasty. This study was designed (i) to determine if local administration of trapidil (triazolopyrimidine) into a vessel wall reduces neointima formation, and (ii) to explore the mechanism involved in the subsequent reduction in cell proliferation. 2. Following balloon angioplasty in 40 anaesthetized New Zealand White rabbits, trapidil (50-200 mg) or its vehicle (saline) was injected into the dilated vessel wall of the right femoral artery. Experimental groups and time of investigation: (I) vehicle (2 weeks, n = 3), (II) trapidil-100 mg (2 weeks, n = 3), (III) vehicle (3 weeks, n = 8), (IV) trapidil-50 mg (3 weeks, n = 5); (V) trapidil-100 mg (3 weeks, n = 9) or (V) trapidil-200 mg (3 weeks, n = 7). 3. After 2 weeks, there was a significant reduction of intimal hyperplasia (expressed as intima to media area ratio) in the trapidil group compared with vehicle (0.44 +/- 0.04 vs 0.93 +/- 0.04, *P < 0.05) and also a significant reduction in cell proliferation (% ratio of BrdU-positive cells to total cell number: vehicle 14 +/- 2% vs trapidil 6 +/- 1%, *P < 0.05). 4. After 3 weeks, there was a dose-dependent reduction of intimal hyperplasia in the trapidil groups compared with vehicle (trapidil 50 mg 1.14 +/- 0.04; trapidil 100 mg 0.91 +/- 0.09*; trapidil 200 mg 0.77 +/- 0.09* vs vehicle 1.67 +/- 0.23, *P < 0.05). 5. Thus, the local administration of trapidil to the rabbit femoral artery reduces the neointima formation, which occurs 2 or 3 weeks after balloon angioplasty via a mechanism, which is dependent on inhibition of cell proliferation.
Zacharowski
K
K
William Harvey Research Institute, St. Bartholomew's and The Royal London School of Medicine and Dentistry, London. kzacharowski@mds.qmw.ac.uk
Schneidmüller
D
D
Ibe
W
W
Grosser
T
T
Buerke
M
M
Meyer
J
J
Darius
H
H
D000800:Angioplasty, Balloon / Q000009:adverse effects*; D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001973:Bromodeoxyuridine / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D005263:Femoral Artery / Q000187:drug effects / Q000502:physiology; D008297:Male; D008954:Models, Biological; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011817:Rabbits; D014192:Trapidil / Q000494:pharmacology*
D000963:Antimetabolites; D010975:Platelet Aggregation Inhibitors; D014192:Trapidil; D001973:Bromodeoxyuridine