This Article Full Text (PDF) References Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Sasseen, B. M. Articles by Wilensky, R. L. Search for Related Content PubMed PubMed Citation Articles by Sasseen, B. M. Articles by Wilensky, R. L. Pubmed/NCBI databases Substance via MeSH Medline Plus Health Information Blood Thinners Hazardous Substances DB HEPARIN Social Bookmarking                         What's this?

Local Delivery of a Hydrophobic Heparin Reduces Neointimal Hyperplasia After Balloon Injury in Rat Carotid but not Pig Coronary Arteries

Laboratory for Experimental Interventional Cardiology, University of Pennsylvania

Brian D. Gray, PhD

PTI Research Inc, Exton, PA

Dov Gal, DVM

Robert Lorinc

Donald C. Carpenter

Zynaxis Inc, Malvern, PA

Bruce D. Klugherz, MD

Robert L. Wilensky, MD

Laboratory for Experimental Interventional Cardiology, University of Pennsylvania

Background: Intimal hyperplasia following percutaneous interventional vascular procedures is a major cause of restenosis. Although heparin inhibits intimal hyperplasia, it has not proven clinically useful in part due to an inadequate duration of intramural drug residence. This study was designed to evaluate the efficacy of local delivery of hydrophobic heparin (PTIR-RS-1), exhibiting increased intramural binding, on neointimal hyperplasia after angioplasty injury.

Methods and Results: PTIR-RS-1 was delivered locally into rat carotid arteries at three doses: 0.1 mM (440 IU), 0.3 mM (1320 IU), or 1.0 mM (4400 IU). Animals were killed at 14 days. In the pig, the doses tested were the low dose in the rat and a high dose 1 log higher. Animals were killed 28 days later. Morphometric analysis was performed to evaluate the intima:media ratio in rats and the normalized neointimal area in pigs. In rats a significant reduction in neointimal to medial area ratio from 0.73 ± 0.15 for control vs 0.80 ± 0.27 for sodium heparin (P = NS) and 0.15 ± 0.07 for the 0.1 mM PTIR-RS-l dose (P < 0.008). In pigs, PTIR-RS-1 the high dose reduced the normalized neointimal area by 16%, a difference that was not statistically significant.

Conclusions: Increased hydrophobicity of heparin reduced neointimal area following balloon overstretch injury in the rat carotid but not the pig coronary artery model. This study attests to the importance of performing studies evaluating the pharmacologic effect of local delivery of a medication in at least two animal models of restenosis.

Key Words: restenosis • local drug delivery • angioplasty • heparin

Journal of Cardiovascular Pharmacology and Therapeutics, Vol. 6, No. 4, 377-383 (2001)
DOI: 10.1177/107424840100600407


CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				J. Ni, A. Waldman, and L. M. Khachigian c-Jun Regulates Shear- and Injury-inducible Egr-1 Expression, Vein Graft Stenosis after Autologous End-to-Side Transplantation in Rabbits, and Intimal Hyperplasia in Human Saphenous Veins J. Biol. Chem., February 5, 2010; 285(6): 4038 - 4048. [Abstract] [Full Text] [PDF]

				U. N K Fonseca, S. G. Nielsen, J. Hau, and A. K. Hansen Permanent catheterization of the carotid artery induces kidney infection and inflammation in the rat Lab Anim, January 1, 2010; 44(1): 46 - 53. [Abstract] [Full Text] [PDF]

				R. S. Schwartz, N. A. Chronos, and R. Virmani Preclinical restenosis models and drug-eluting stents: Still important, still much to learn J. Am. Coll. Cardiol., October 6, 2004; 44(7): 1373 - 1385. [Abstract] [Full Text] [PDF]