Induction of thrombolysis and prevention of thrombus formation by local drug delivery with a double-occlusion balloon catheter.
The efficacy of the local delivery of an antithrombotic drug in preventing thrombosis and enabling thrombolysis was investigated in 29 dogs. An antithrombotic drug (heparin, 25 U/kg), or an antithrombin (argatroban, 0.05 mg/kg) was infused into injured canine iliac arteries, using a double-occlusion balloon catheter, and the preventive effect of the drug was evaluated. Local delivery of low-dose tissue-type plasminogen activator (t-PA; Tisokinase, 50,000 U; Kowa, Nagoya and Asahi Chemical Industries, Fuji, Japan) into thrombosed canine iliac arteries, using the same catheter, or intravenous infusion of low-dose or high-dose t-PA (30,000 U/kg) was also performed. Angiographically, stenotic thrombosis was 2% by local delivery of argatroban and 7% by local delivery of heparin (P < 0.01 vs each control; 47% and 51% respectively). Thrombotic stenosis, as observed by angiography, decreased from 91% to 9% after local delivery of t-PA, and from 94% to 52% in controls. Local delivery of t-PA effectively reduced the thrombus size (P < 0.01 vs control). After systemic intravenous delivery of low-dose t-PA, no reduction of residual thrombotic stenosis, was observed. Reduction of residual thrombotic stenosis after intravenous delivery of high-dose t-PA, was similar to that achieved by local delivery of the drug. Angioscopy demonstrated a similar trend. High-dose drug delivery reduced systemic coagulability. Local delivery of an antithrombotic drug, using a double-occlusion balloon catheter, effectively prevented thrombus formation, and local delivery of t-PA induced thrombolysis without exerting a significant influence on coagulability.
Second Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
T
T
Tomaru
Y
Y
Fujimori
F
F
Nakamura
N
N
Aoki
Y
Y
Sakamoto
K
K
Kawai
M
M
Omata
Y
Y
Uchida
D017546:Angioscopy; D000818:Animals; D000925:Anticoagulants / Q000008:administration & dosage* / Q000627:therapeutic use; D000991:Antithrombins / Q000008:administration & dosage* / Q000627:therapeutic use; D001120:Arginine / Q000031:analogs & derivatives; D002404:Catheterization / Q000295:instrumentation*; D017023:Coronary Angiography; D003328:Coronary Thrombosis / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control; D003331:Coronary Vessels; D004195:Disease Models, Animal; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D006493:Heparin / Q000008:administration & dosage* / Q000627:therapeutic use; D015552:Injections, Intralesional; D010875:Pipecolic Acids / Q000008:administration & dosage* / Q000627:therapeutic use; D010960:Plasminogen Activators / Q000008:administration & dosage* / Q000627:therapeutic use; D013449:Sulfonamides; D015912:Thrombolytic Therapy / Q000295:instrumentation* / Q000379:methods; D016896:Treatment Outcome
D000925:Anticoagulants; D000991:Antithrombins; D010875:Pipecolic Acids; D013449:Sulfonamides; D006493:Heparin; D001120:Arginine; D010960:Plasminogen Activators; C031942:argatroban