Additive fibrinolysis by recombinant tissue-type plasminogen activator (r-t-PA) and recombinant single-chain urokinase type plasminogen activator (r-scu-PA) in rabbit pulmonary thrombosis.
The mode of interaction between recombinant tissue-type plasminogen activator (r-t-PA) and recombinant single-chain urokinase-type plasminogen activator (r-scu-PA) has been investigated in in vivo experiments. 125J-fibrin-labeled clots were embolized via a jugular vein into the lungs of anesthetized rabbits. In saline-treated control rabbits the spontaneous lysis, shown as decrease in radioactivity of the retrieved clots, amounted to 10.4 +/- 1.4% at 255 min after the pulmonary embolization. r-t-PA (0.464 - 4.64 micrograms/kg.min) and r-scu-PA (4.64 - 46.4 microns/kg.min), infused for 60 min, produced dose-dependent lytic effects to a similar extent (maximum lysis rate 53.9 +/- 5.8 and 55.4 +/- 7.2%, resp.). When various ratios of submaximal doses of r-t-PA and r-scu-PA were combined the lytic effects of these combinations were not higher than the calculated summation of the lysis rates by the single components. The fractional dose-response curves of r-t-PA and r-scu-PA and the combination of them, fitted by linear regression analysis, are overlaying each other. The results indicate that r-t-PA and r-scu-PA produce in vivo lysis in rabbits with pulmonary embolized clots in a purely additive manner.
Schneider
J
J
Grünenthal GmbH, Center of Research, Aachen, FRG.
Friderichs
E
E
Günzler
W A
WA
Flohé
L
L
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005343:Fibrinolytic Agents / Q000008:administration & dosage*; D008297:Male; D010960:Plasminogen Activators / Q000008:administration & dosage*; D011655:Pulmonary Embolism / Q000188:drug therapy*; D011817:Rabbits; D011994:Recombinant Proteins / Q000008:administration & dosage; D015912:Thrombolytic Therapy; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage*; D014568:Urokinase-Type Plasminogen Activator / Q000008:administration & dosage*
D005343:Fibrinolytic Agents; D011994:Recombinant Proteins; D010960:Plasminogen Activators; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator