Separate and Combined Effects of Local and Continuous Intravenous Administration of β-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 β-cyclodextrin tetradecasulfate on neointimal formation and arterial damage following angioplasty. Methods and Results: Fifty-two pigs randomized into four groups underwent coronary artery angioplasty: 1) control, 2) continuous intravenous infusion of 100 mg/kg/d of β-cyclodextrin tetradecasulfate, 3) intramural delivery of 1250 mg β-cyclodextrin tetradecasulfate, 4) intramural delivery of 1250 mg β-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 β-cyclodextrin tetradecasulfate groups had a decreased normalized neointima area: control, 3.03 ± 0.75 mm2; intravenous, 1.67 ± 0.73 mm2 (40% decrease; P < 10-7); intravenous plus local, 1.95 ± 0.76 mm2 (30% decrease; P < 10-5). There was no difference in neointimal response following local β-cyclodextrin tetradecasulfate delivery only (2.82 ± 1.14 mm2). 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 β-cyclodextrin tetradecasulfate substantially reduced intimal hyperplasia, while intramural delivery had no effect, indicating that a single bolus of β-cyclodextrin tetradecasulfate did not reduce intimal hyperplasia. There was no additive effect of local intramural delivery of β-cyclodextrin tetradecasulfate. However, local delivery of β-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.