title: Separate and combined effects of local and continuous intravenous administration of beta-cyclodextrin tetradecasulfate on intimal hyperplasia after angioplasty in porcine coronary arteries.
abstract: BACKGROUND
  Beta-Cyclodextrin tetradecasulfate binds fibroblast growth factors and possesses anticoagulant properties. This study was designed to assess the separate and combined effects of local intramural delivery and intravenous administration of beta-cyclodextrin tetrade-casulfate on neointimal formation and arterial damage following angioplasty.
  
  
  RESULTS
  Fifty-two pigs randomized into four groups underwent coronary artery angioplasty: 1) control, 2) continuous intravenous infusion of 100 mg/kg/d of beta-cyclodextrin tetradecasulfate, 3) intramural delivery of 1250 mg beta-cyclodextrin tetradecasulfate, 4) intramural delivery of 1250 mg beta-cyclodextrin tetradecasulfate followed by continuous intravenous infusion of 100 mg/kg/d. Fourteen days after injury, morphometric analysis revealed that arteries randomized to the intravenous beta-cyclodextrin tetradecasulfate groups had a decreased normalized neointima area: control, 3.03 +/- 0.75 mm(2); intravenous, 1.67 +/- 0.73 mm(2) (40% decrease; P < 10(-7)); intravenous plus local, 1.95 +/- 0.76 mm(2) (30% decrease; P < 10(-5)). There was no difference in neointimal response following local beta-cyclodextrin tetradecasulfate delivery only (2.82 +/- 1.14 mm(2)). Coronary arterial damage, defined as aneurysm, dissection, adventitial rupture, and retromedial hematoma was similar in all groups (12% in control and local groups, 10% in the intravenous group, 14% in the intravenous plus local; NS). Bleeding complications were more frequent in the intravenous and intravenous plus local groups compared to the local and control groups (23%vs 7.6% and 0%, respectively; P < 0.05).
  
  
  CONCLUSIONS
  Continuous intravenous administration of beta-cyclodextrin tetradecasulfate substantially reduced intimal hyperplasia, while intramural delivery had no effect, indicating that a single bolus of beta-cyclodextrin tetradecasulfate did not reduce intimal hyperplasia. There was no additive effect of local intramural delivery of beta-cyclodextrin tetradecasulfate. However, local delivery of beta-cyclodextrin tetradecasulfate induced less bleeding complications and did not lead to additional arterial injury, indicating that local delivery of an anticoagulant does not cause additional arterial injury.
authors.affiliation: Department of Medicine (Cardiovascular Division) of the University of Pennsylvania, 19104, USA.
authors.forename: Nicolas F
authors.initials: NF
authors.lastname: Meneveau
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Klugherz
authors.forename: Brahim
authors.initials: B
authors.lastname: Chaquor
authors.forename: Michael A
authors.initials: MA
authors.lastname: Golden
authors.forename: Madeleine M
authors.initials: MM
authors.lastname: Jouille
authors.forename: Edward
authors.initials: E
authors.lastname: Macarek
authors.forename: Paul B
authors.initials: PB
authors.lastname: Weisz
authors.forename: Robert L
authors.initials: RL
authors.lastname: Wilensky
mesh_terms: D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects*; D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects* / Q000473:pathology; D003505:Cyclodextrins / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D004562:Electrocardiography; D006965:Hyperplasia / Q000473:pathology / Q000517:prevention & control; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D011897:Random Allocation; D013552:Swine; D017539:Tunica Intima / Q000187:drug effects* / Q000293:injuries / Q000473:pathology; D047392:beta-Cyclodextrins
chemical_list: D003505:Cyclodextrins; D047392:beta-Cyclodextrins; C064089:beta-cyclodextrin tetradecasulfate