Local delivery of antithrombotic drug prevents restenosis after balloon angioplasty in atherosclerotic rabbit artery.
We investigated the ability of various antithrombotic drugs, delivered locally, to prevent restenosis after angioplasty in hypercholesterolemic rabbits. After dilating atherosclerotic iliac stenoses by balloon angioplasty, a low dose of heparin or a new antithrombotic drug, such as low molecular weight heparin (fragmin), argatroban, or batroxobin, was delivered locally using the balloon double-occlusion technique. In 1 group, high-dose heparin was administered intravenously. Animals that received no drugs served as a control group. After angioplasty, the stenotic segment was dilated and the mean percentage luminal stenosis fell from 89% to 9% in the group that received locally delivered heparin, from 88% to 7% in the group that received locally delivered argatroban, from 87% to 11% in the group that received locally delivered fragmin, from 88% to 15% in the group that received locally delivered batroxobin, from 82% to 18% in the group that received i.v. heparin (p < 0.0001 compared with before angioplasty in each case), and from 84% to 17% in the control group (p < 0.005 compared with before angioplasty). Twenty-eight days after angioplasty, the percentage luminal stenosis remained at 14% in the group that received locally delivered argatroban, 15% in the group that received locally delivered fragmin, and 28% in the group that received locally delivered batroxobin, whereas it increased to 45% in the group that received i.v. heparin, 30% in the group that received locally delivered heparin and 72% in the control group (p < 0.05 compared with after angioplasty in each case). Thus, local delivery low doses of new antithrombotic drugs prevents restenosis after angioplasty without affecting systemic coagulability; heparin, whether administered locally or intravenously, was less effective than the new drugs in preventing restenosis.
Tomaru
T
T
Second Department of Internal Medicine, University of Tokyo, Japan.
Fujimori
Y
Y
Morita
T
T
Aoki
N
N
Sakamoto
Y
Y
Nakamura
F
F
Omata
M
M
Uchida
Y
Y
D000792:Angiography; D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects*; D017546:Angioscopy; D000818:Animals; D000991:Antithrombins / Q000494:pharmacology*; D001120:Arginine / Q000031:analogs & derivatives; D001161:Arteriosclerosis / Q000188:drug therapy*; D012103:Batroxobin / Q000494:pharmacology; D003251:Constriction, Pathologic / Q000188:drug therapy / Q000517:prevention & control; D005343:Fibrinolytic Agents / Q000494:pharmacology; D016650:Fluorescein-5-isothiocyanate; D006495:Heparin, Low-Molecular-Weight / Q000494:pharmacology; D007083:Iliac Artery / Q000187:drug effects / Q000473:pathology; D008297:Male; D018613:Microscopy, Confocal; D010875:Pipecolic Acids / Q000494:pharmacology; D011817:Rabbits; D013449:Sulfonamides; D013927:Thrombosis / Q000188:drug therapy / Q000517:prevention & control
D000991:Antithrombins; D005343:Fibrinolytic Agents; D006495:Heparin, Low-Molecular-Weight; D010875:Pipecolic Acids; D013449:Sulfonamides; D001120:Arginine; D012103:Batroxobin; D016650:Fluorescein-5-isothiocyanate; C031942:argatroban