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


CONCLUSIONS
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.
Tian
Wen
W
Department of Cardiology and Angiology, University of Münster, Germany.
Kuhlmann
Michael T
MT
Pelisek
Jaroslav
J
Scobioala
Sergiu
S
Quang
Trong Hung
TH
Hasib
Lekbira
L
Klocke
Rainer
R
Jahn
Uli-Ruediger
UR
Nikol
Sigrid
S
D000704:Analysis of Variance; D000800:Angioplasty, Balloon; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D003238:Connective Tissue / Q000098:blood supply* / Q000187:drug effects*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology* / Q000601:surgery*; D005263:Femoral Artery / Q000187:drug effects / Q000293:injuries / Q000473:pathology; D005455:Fluorescent Antibody Technique; D006083:Graft Occlusion, Vascular / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D006965:Hyperplasia / Q000188:drug therapy; D007150:Immunohistochemistry; D007269:Injections, Intra-Arterial; D019394:Ki-67 Antigen / Q000187:drug effects / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000187:drug effects; D017239:Paclitaxel / Q000008:administration & dosage / Q000494:pharmacology*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000187:drug effects / Q000378:metabolism; D012107:Research Design; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013552:Swine; D017539:Tunica Intima / Q000187:drug effects / Q000473:pathology; D017540:Tunica Media / Q000187:drug effects / Q000473:pathology; D014841:von Willebrand Factor / Q000187:drug effects / Q000378:metabolism
D000972:Antineoplastic Agents, Phytogenic; D019394:Ki-67 Antigen; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D014841:von Willebrand Factor; D017239:Paclitaxel