Local treatment with an antithrombotic drug reduces thrombus size in coronary and peripheral thrombosed arteries.
Since the treatment of thrombotic disease by antithrombotic drugs may be associated with bleeding complications, a local delivery technique for administration of the drug may be useful. The efficacy of low-dose local delivery of an antithrombotic drug on thrombosis was investigated in 73 dogs. The antithrombotic drug (heparin, 25 U/kg, antithrombin: argatroban, 0.05 mg/kg, or defibrinogenating agent: batroxobin, 0.05 U/kg) was infused locally to a 1-h-old thrombus, and no drug was given in controls. The effect of the local delivery on the thrombus was evaluated. Low- and high-dose systemic drug delivery was also evaluated. The mean reduction in thrombotic coronary stenosis observed by angiography was 30.3% with argatroban, 22% with heparin, and 20.8% with batroxobin (P < 0.005 vs controls). Systemic delivery of low-dose heparin or argatroban did not induce any change in thrombus size. With high-dose systemic drug delivery (heparin 250 U/kg, argatroban 0.5 mg/kg), the mean reduction of thrombotic stenosis was 15.2% with heparin and 32.8% with argatroban (P < 0.005 vs controls). In the iliac arterial thrombosis, after local delivery of the drugs, the mean reduction of thrombotic stenosis observed by angiography was 24.4% in the argatroban group, and 19.2% in the heparin group (P < 0.05 vs controls, respectively). With high-dose systemic heparin delivery, the mean reduction of the thrombotic stenosis was 13.2% (P < 0.01 vs control). Angioscopy also demonstrated a similar trend. The high-dose drug delivery reduced systemic coagulability. Thus, local delivery of an antithrombotic agent can reduce the thrombus size in the coronary and iliac arteries without having any significant influence on coagulability.
Second Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
T
T
Tomaru
F
F
Nakamura
N
N
Aoki
Y
Y
Sakamoto
M
M
Omata
Y
Y
Uchida
D017546:Angioscopy; D000818:Animals; D000991:Antithrombins / Q000008:administration & dosage* / Q000627:therapeutic use; D001120:Arginine / Q000031:analogs & derivatives; D012103:Batroxobin / Q000008:administration & dosage* / Q000627:therapeutic use; D017023:Coronary Angiography; D003328:Coronary Thrombosis / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D003331:Coronary Vessels; D004195:Disease Models, Animal; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D006493:Heparin / Q000008:administration & dosage* / Q000627:therapeutic use; D007262:Infusions, Intravenous; D015552:Injections, Intralesional; D010875:Pipecolic Acids / Q000008:administration & dosage* / Q000627:therapeutic use; D012016:Reference Values; D013449:Sulfonamides; D016896:Treatment Outcome
D000991:Antithrombins; D005343:Fibrinolytic Agents; D010875:Pipecolic Acids; D013449:Sulfonamides; D006493:Heparin; D001120:Arginine; D012103:Batroxobin; C031942:argatroban