Thrombolytic therapy in canine pulmonary embolism. Comparative effects of urokinase and recombinant tissue plasminogen activator.
We compared thrombolytic and pulmonary hemodynamic effects of recombinant tissue plasminogen activator (rtPA) and urokinase (UK) in canine micropulmonary thromboembolism. Dogs were embolized with radioactive autologous blood clot to increase mean pulmonary artery pressure (from 13 to 34 mm Hg, p less than 0.005) and decrease cardiac output (2.5 to 1.6 L min, p less than 0.005). Four groups of six dogs were treated. We employed two doses of UK, 30,000 U/kg (UK30) and 60,000 U/kg (UK60), and two doses of rtPA, 1 mg/kg (rtPA1) and 2 mg/kg (rtPA2). Drugs were infused over 15 min. Rate and extent of pulmonary thrombolysis were assessed by continuously counting over both lung fields with a gamma camera. Compared with treatment with UK, both rtPA regimes significantly increased thrombolysis. Mean total pulmonary thrombolysis was 14 and 23% with UK30 and UK60, respectively, and 35 and 43% with rtPA1 and rtPA2. Corresponding to the increased thrombolysis, pulmonary hemodynamics improved most with rtPA. From 90 min to 3 h, pulmonary artery pressure was significantly lower with both rtPA regimes than with either UK regime. These results indicate, at least in the model employed, that compared with treatment with UK, pulmonary thrombolysis and corresponding hemodynamic improvement are greatest with rtPA.
Prewitt
R M
RM
Department of Medicine, University of Manitoba, Winnipeg, Canada.
Hoy
C
C
Kong
A
A
Gu
S A
SA
Greenberg
D
D
Cook
R
R
Chan
S M
SM
Ducas
J
J
D000818:Animals; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D008168:Lung / Q000187:drug effects / Q000503:physiopathology; D011655:Pulmonary Embolism / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D011994:Recombinant Proteins / Q000627:therapeutic use; D015912:Thrombolytic Therapy / Q000379:methods*; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage / Q000627:therapeutic use*; D014568:Urokinase-Type Plasminogen Activator / Q000008:administration & dosage / Q000627:therapeutic use*
D011994:Recombinant Proteins; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator