Paclitaxel delivered to adventitia attenuates neointima formation without compromising re-endothelialization after angioplasty in a porcine restenosis model.

Abstract

PURPOSE:

To investigate the effect of paclitaxel delivered into the adventitia of pig femoral arteries on neointima formation and hyperplasia as well as re-endothelialization.

METHODS:

Paclitaxel or vehicle was delivered into the adventitia of pig femoral arteries using a needle injection catheter following balloon overstretch. Arteries were then serially examined by angiography, Evan's blue staining, morphometry, and immunohistochemistry for up to 12 weeks.

RESULTS:

Local adventitial delivery of paclitaxel significantly attenuated neointima formation. The area of neointima (0.41+/-0.17 versus 2.75+/-0.81 mm(2), p<0.01), the ratio of intima to media (0.12+/-0.05 versus 0.86+/-0.35, p<0.05), and the degree of stenosis (12.80%+/-3.13% versus 47.06%+/-7.25%, p<0.01) were significantly lower in the paclitaxel-treated group compared to controls. Furthermore, cell proliferation was significantly diminished following adventitial delivery of paclitaxel from day 3 to 21 compared to controls. Complete re-endothelialization was observed 3 weeks after intervention in both groups of arteries treated with paclitaxel or vehicle alone.

CONCLUSION:

Paclitaxel delivered into the adventitia of pig femoral arteries effectively attenuates neointima formation after angioplasty without compromising re-endothelialization. Adventitial drug delivery may therefore be an alternative to drug-eluting stents for the prevention of restenosis.

• Authors: Wen Tian, Michael T Kuhlmann, Jaroslav Pelisek, Sergiu Scobioala, Trong Hung Quang, Lekbira Hasib, Rainer Klocke, Uli-Ruediger Jahn, Sigrid Nikol
• Journal: Journal of endovascular therapy : an official journal of the International Society of Endovascular Specialists (J Endovasc Ther) Vol. 13 Issue 5 Pg. 616-29 (Oct 2006) ISSN: 1526-6028 [Print] United States
• PMID: 17042659 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents, Phytogenic
• Ki-67 Antigen
• Platelet Endothelial Cell Adhesion Molecule-1
• von Willebrand Factor
• Paclitaxel

Topics

• Analysis of Variance
• Angioplasty, Balloon
• Animals
• Antineoplastic Agents, Phytogenic (pharmacology)
• Cell Proliferation (drug effects)
• Connective Tissue (blood supply, drug effects)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Endothelial Cells (drug effects)
• Endothelium, Vascular (drug effects, metabolism, pathology, surgery)
• Femoral Artery (drug effects, injuries, pathology)
• Fluorescent Antibody Technique
• Graft Occlusion, Vascular (metabolism, pathology, therapy)
• Hyperplasia (drug therapy)
• Immunohistochemistry
• Injections, Intra-Arterial
• Ki-67 Antigen (drug effects, metabolism)
• Myocytes, Smooth Muscle (drug effects)
• Paclitaxel (administration & dosage, pharmacology)
• Platelet Endothelial Cell Adhesion Molecule-1 (drug effects, metabolism)
• Research Design
• Reverse Transcriptase Polymerase Chain Reaction
• Swine
• Tunica Intima (drug effects, pathology)
• Tunica Media (drug effects, pathology)
• von Willebrand Factor (drug effects, metabolism)