Martin U, Sponer G, Strein K
Department of Pharmacology, Boehringer Mannheim GmbH, Germany.
J Cardiovasc Pharmacol. 1993 Mar;21(3):455-61. doi: 10.1097/00005344-199303000-00016.
We used a canine model of embolic pulmonary hypertension induced by intravenous (i.v.) injection of autologous thrombi to evaluate whether the novel recombinant plasminogen activator (r-PA) BM 06.022 reversed pulmonary hypertension. The effects of BM 06.022 after bolus injection were compared with those of vehicle, alteplase, urokinase, and anistreplase in 6 dogs per group. Thirty minutes after initiation of treatment, the decrease in pulmonary artery pressure (PAP) caused by a bolus of 200 kU/kg (0.35 mg/kg) BM 06.022 was greater (p < 0.05) than that caused by a 2-h infusion of 1.33 mg/kg alteplase or of 40,000 U/kg urokinase and that caused by a bolus of 0.4 U/kg anistreplase but not that caused by a 15-min infusion of 1 mg/kg alteplase. At 3 h, all thrombolytic agents had reduced PAP equally. The greatest measured plasma concentration of BM 06.022 was higher (p < 0.05) than that of 2-h infused alteplase (4,498 +/- 716 vs. 519 +/- 119 IU/ml). We conclude that because of its bolus-pharmacokinetics, BM 06.022 more rapidly reversed thromboembolic pulmonary hypertension than did 2-h infusion of alteplase or urokinase or a bolus of anistreplase.
我们使用静脉注射自体血栓诱导的犬栓塞性肺动脉高压模型，来评估新型重组纤溶酶原激活剂（r-PA）BM 06.022是否能逆转肺动脉高压。将每组6只犬静脉推注BM 06.022后的效果与给予赋形剂、阿替普酶、尿激酶和茴酰化纤溶酶原链激酶激活剂复合物（anistreplase）后的效果进行比较。治疗开始30分钟后，静脉推注200 kU/kg（0.35 mg/kg）BM 06.022引起的肺动脉压（PAP）下降幅度大于静脉输注1.33 mg/kg阿替普酶或40,000 U/kg尿激酶2小时引起的下降幅度，也大于静脉推注0.4 U/kg茴酰化纤溶酶原链激酶激活剂复合物引起的下降幅度，但小于静脉输注1 mg/kg阿替普酶15分钟引起的下降幅度。在3小时时，所有溶栓剂对PAP的降低程度相同。所测得的BM 06.022的最大血浆浓度高于静脉输注2小时的阿替普酶（4,498±716 vs. 519±119 IU/ml，p<0.05）。我们得出结论，由于其推注给药的药代动力学特点，BM 06.022比静脉输注2小时的阿替普酶或尿激酶或静脉推注茴酰化纤溶酶原链激酶激活剂复合物能更迅速地逆转血栓栓塞性肺动脉高压。
