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 det ermine if local administration of trapidil (triazolopyrimidine) into a vess el wall reduces neointima formation. and (ii) to explore the mechanism invo lved in the subsequent reduction in cell proliferation. 2 Following balloon angioplasty in 40 anaesthetized New Zealand White rabbi ts, trapidil (50-200 mg) or its vehicle (saline) was injected into the dila ted vessel wall of the right femoral artery. Experimental groups and time o f investigation: (I) vehicle (2 weeks, n = 3), (II) trapidil-100 mg (2 week s. 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 wit h vehicle (0.44+/-0.04 vs 0.93+/-0.04, *P<0.05) and also a significant redu ction in cell proliferation (% ratio of BrdU-positive cells to total cell n umber: vehicle 14+/-2% vs trapidil 6+/-1%, *P<0.05). 4 After 3 weeks, there was a dose-dependent reduction of intimal hyperplasi a in the trapidil groups compared with vehicle (trapidil 50 mg 1.14+/-0.04; trapidil 100 mi 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 r educes the neointima formation, which occurs 2 or 3 weeks after balloon ang ioplasty via a mechanism, which is dependent on inhibition of cell prolifer ation.