Tomaru T, Nakamura F, Aoki N, Sakamoto Y, Omata M, Uchida Y
Second Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
Heart Vessels. 1996;11(3):133-44. doi: 10.1007/BF01745171.
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.
由于抗血栓药物治疗血栓性疾病可能会伴有出血并发症,药物的局部递送技术可能会很有用。在73只犬中研究了低剂量局部递送抗血栓药物对血栓形成的疗效。将抗血栓药物(肝素,25 U/kg;抗凝血酶:阿加曲班,0.05 mg/kg;或去纤维蛋白原剂:巴曲酶,0.(此处原文有误,推测为0.05)U/kg)局部注入1小时龄的血栓中,对照组不给予药物。评估局部递送对血栓的影响。还评估了低剂量和高剂量全身药物递送。血管造影观察到,阿加曲班使血栓性冠状动脉狭窄的平均降低率为30.3%,肝素为22%,巴曲酶为20.8%(与对照组相比,P < 0.005)。低剂量肝素或阿加曲班的全身递送未引起血栓大小的任何变化。高剂量全身药物递送(肝素250 U/kg,阿加曲班0.5 mg/kg)时,肝素使血栓性狭窄的平均降低率为15.2%,阿加曲班为32.8%(与对照组相比,P < 0.005)。在髂动脉血栓形成中,局部递送药物后,血管造影观察到阿加曲班组血栓性狭窄的平均降低率为24.4%,肝素组为19.2%(分别与对照组相比,P < 0.05)。高剂量全身递送肝素时,血栓性狭窄的平均降低率为13.2%(与对照组相比,P < 0.01)。血管内镜检查也显示出类似趋势。高剂量药物递送降低了全身凝血能力。因此,局部递送抗血栓剂可减小冠状动脉和髂动脉中的血栓大小,而对凝血能力无任何显著影响。