Local administration of ramiprilat is less effective than oral ramipril inpreventing restenosis after balloon angoplasty in an animal model

PURPOSE: To test the hypothesis that local administration of an angiotensin converting enzyme (ACE) inhibitor via a microporous balloon catheter would be more effective than oral administration of ACE inhibitor in preventing neointima formation after balloon angioplasty, MATERIALS AND METHODS: Neointima formation was induced by balloon denudatio n followed by 0.5% cholesterol diet in 29 New Zealand White rabbits, Direct ly after denudation, local administration of 1.8 mg of ramiprilat (n = 7) o r saline (n = 7) with a microporous balloon catheter at a pressure of 3 atm was performed. Both groups additionally received ramipril orally (1 mg/d), Seven animals were treated exclusively with oral ramipril, The control gro up was fed a 0.5% cholesterol diet and given no medication (n = 8), Six wee ks after intervention, the animals were killed and morphometric and immunoh istologic analyses were performed. RESULTS: Oral administration of ramipril resulted in a significant reductio n of plaque area (-66%, P < .05), Oral and local administration of the ACE inhibitor was followed by a nonsignificant reduction of the neointimal area (-17%), Local administration of saline combined with oral ramipril failed to prevent neointima formation (reduction of 6%, NS). CONCLUSION: Oral administration of ramipril resulted in a significant reduc tion of neointimal proliferation in New Zealand White rabbits, The possible benefit of an additional administration of local ramiprilat was diminished by an excessive neointimal hyperplasia, which was most likely caused by th e inherent vessel trauma with use of the microporous balloon catheter.