Abstract
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 μg/kg min) and r-scu-PA (4.64 - 46.4 μm/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.
Published Version
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