Complete inhibition of intimal hyperplasia by perivascular delivery of paclitaxel in balloon-injured rat carotid arteries.
OBJECTIVE
To determine whether perivascular delivery of paclitaxel prevents luminal narrowing after balloon injury by inhibiting intimal hyperplasia.


METHODS
Immediately after balloon injury of the entire left common carotid artery, three slow-release formulations of paclitaxel or control formulations without drug were applied around a distal segment of the artery. The noninjured right carotid arteries were evaluated as a control. The animals were maintained for 14 and 28 days (n = 5 in each group at each time interval). Histology, immunohistochemistry, and morphometric analysis were performed.


RESULTS
Injured nontreated arteries exhibited a pronounced intimal hyperplasia (0.185 +/- 0.01 mm2 at 14 days and 0.189 +/- 0.01 mm2 at 28 days) and a marked reduction in luminal area (44% at 14 days and 43% at 28 days). Medial area and the number of medial cells increased by 44% and 45%, respectively, at 14 days, and by 22% and 37%, respectively, at 28 days. Injured arteries treated with perivascular paclitaxel did not show any intimal hyperplasia, and luminal area was increased in five of six groups and was unchanged in one group. These arteries had an increased medial area but they had fewer medial cells than noninjured arteries. Injured arteries treated with control implants without paclitaxel exhibited intimal hyperplasia and luminal narrowing.


CONCLUSIONS
Perivascular slow release of paclitaxel totally inhibits intimal hyperplasia and prevents luminal narrowing after balloon injury. Because of its efficacy, perivascular paclitaxel represents a possible approach for prevention of restenosis in humans.
Signore
P E
PE
Angiotech Pharmaceuticals, Vancouver, BC, Canada.
Machan
L S
LS
Jackson
J K
JK
Burt
H
H
Bromley
P
P
Wilson
J E
JE
McManus
B M
BM
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000800:Angioplasty, Balloon / Q000009:adverse effects*; D000818:Animals; D017536:Carotid Artery, Common / Q000187:drug effects / Q000473:pathology*; D006965:Hyperplasia; D017239:Paclitaxel / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D017539:Tunica Intima / Q000187:drug effects / Q000473:pathology*
D020533:Angiogenesis Inhibitors; D017239:Paclitaxel