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.

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 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: Nicolas F Meneveau, Bruce D Klugherz, Brahim Chaquor, Michael A Golden, Madeleine M Jouille, Edward Macarek, Paul B Weisz, Robert L Wilensky
• Journal: Journal of cardiovascular pharmacology and therapeutics (J Cardiovasc Pharmacol Ther) Vol. 8 Issue 1 Pg. 53-60 (Mar 2003) ISSN: 1074-2484 [Print] United States
• PMID: 12652330 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cyclodextrins
• beta-Cyclodextrins
• beta-cyclodextrin tetradecasulfate

Topics

• Angioplasty, Balloon, Coronary (adverse effects)
• Animals
• Coronary Vessels (drug effects, pathology)
• Cyclodextrins (administration & dosage, adverse effects, pharmacology)
• Electrocardiography
• Hyperplasia (pathology, prevention & control)
• Infusions, Intravenous
• Injections, Intravenous
• Random Allocation
• Swine
• Tunica Intima (drug effects, injuries, pathology)
• beta-Cyclodextrins