Rapid reversal of canine thromboembolic pulmonary hypertension by bolus injection of the novel recombinant plasminogen activator BM 06.022.
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.
Martin
U
U
Department of Pharmacology, Boehringer Mannheim GmbH, Germany.
Sponer
G
G
Strein
K
K
D000818:Animals; D016255:Anistreplase / Q000627:therapeutic use; D004195:Disease Models, Animal; D004285:Dogs; D005260:Female; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006439:Hemodynamics / Q000187:drug effects; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000209:etiology; D008297:Male; D011655:Pulmonary Embolism / Q000150:complications / Q000188:drug therapy*; D011994:Recombinant Proteins / Q000627:therapeutic use; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*; D014568:Urokinase-Type Plasminogen Activator / Q000627:therapeutic use
D005343:Fibrinolytic Agents; D011994:Recombinant Proteins; D016255:Anistreplase; C087896:reteplase; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator