Separate and combined effects of local and continuous intravenous administration of beta-cyclodextrin tetradecasulfate on intimal hyperplasia after angioplasty in porcine coronary arteries.
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.
Meneveau
Nicolas F
NF
Department of Medicine (Cardiovascular Division) of the University of Pennsylvania, 19104, USA.
Klugherz
Bruce D
BD
Chaquor
Brahim
B
Golden
Michael A
MA
Jouille
Madeleine M
MM
Macarek
Edward
E
Weisz
Paul B
PB
Wilensky
Robert L
RL
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
D003505:Cyclodextrins; D047392:beta-Cyclodextrins; C064089:beta-cyclodextrin tetradecasulfate