title: Local administration of ramiprilat is less effective than oral ramipril in preventing restenosis after balloon angioplasty in an animal model.
abstract: OBJECTIVE
  To test the hypothesis that local administration of 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.
  
  
  METHODS
  Neointima formation was induced by balloon denudation followed by 0.5% cholesterol diet in 29 New Zealand White rabbits. Directly after denudation, local administration of 1.8 mg of ramiprilat (n = 7) or 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 group was fed a 0.5% cholesterol diet and given no medication (n = 8). Six weeks after intervention, the animals were killed and morphometric and immunohistologic analyses were performed.
  
  
  RESULTS
  Oral administration of ramipril resulted in a significant reduction of placque 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 neointimal formation (reduction of 6%, NS).
  
  
  CONCLUSIONS
  Oral administration of ramipril resulted in a significant reduction 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 the inherent vessel trauma with use of the microporous balloon catheter.
authors.affiliation: Department of Diagnostic Radiology, Eberhard-Karls-University, Tübingen, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Kalinowski
authors.forename: G
authors.initials: G
authors.lastname: Tepe
authors.forename: A
authors.initials: A
authors.lastname: Schieber
authors.forename: U
authors.initials: U
authors.lastname: Brehme
authors.forename: B
authors.initials: B
authors.lastname: Bruck
authors.forename: C M
authors.initials: CM
authors.lastname: Erley
authors.forename: C D
authors.initials: CD
authors.lastname: Claussen
authors.forename: S H
authors.initials: SH
authors.lastname: Duda
mesh_terms: D000284:Administration, Oral; D000800:Angioplasty, Balloon / Q000009:adverse effects*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage*; D000818:Animals; D001012:Aorta, Abdominal / Q000473:pathology; D006083:Graft Occlusion, Vascular / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D007269:Injections, Intra-Arterial; D008297:Male; D009389:Neovascularization, Pathologic / Q000150:complications / Q000473:pathology / Q000517:prevention & control; D011817:Rabbits; D017257:Ramipril / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D055502:Secondary Prevention; D016896:Treatment Outcome; D017539:Tunica Intima / Q000473:pathology
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; C052549:ramiprilat; D017257:Ramipril