359 Fibrinolysis by two-chain urokinase-type plasminogen activator cleaved at arginine-156 by thrombin

Broeze, Robert J.; Abercrombie, David M.; Buchinski, B.; Salvato, Kathleen A.; Stump, David C.; Vovis, G.

doi:10.1016/0268-9499(88)90706-0

Cited by 3 publications

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“…Therefore, it is possible that, in dogs which did not receive heparin, increased thrombin activity may have limited the thrombolytic potential of pro-urokinase, resulting in less clot lysis in these animals. However, literature reports have shown that prourokinase subjected to thrombin treatment resulted in a twochain entity which still retained the ability to produce in vivo clot lysis (36,37) . This suggests that pro-urokinase inactivation by thrombin is not complete, and that this factor may play only a minor role in the results described in our studies.…”

Section: Discussionmentioning

confidence: 99%

Recombinant Pro-Urokinase Requires Heparin for Optimal Clot Lysis and Restoration of Blood Flow in a Canine Femoral Artery Thrombosis Model

et al. 1993

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SummaryHeparin is often used as an adjunct to thrombolytic therapy in order to prevent reocclusion of the patent vessels in patients with thrombotic disease. Controversy exists as to whether heparin is required for effective clot lysis with tissue-type plasminogen activator, while in vitro data and small scale clinical trials have suggested an enhancement of pro-urokinase efficacy by heparin. The present study was conducted to determine whether heparin pre-treatment is required to produce optimal clot lysis and blood flow restoration in response to recombinant pro-urokinase (r-proUK). In four groups of dogs, blood clots labelled with 125Iodine were formed in the femoral artery and were monitored continuously for loss of counts as an indicator of clot lysis. Femoral artery blood flow was measured simultaneously. Group 1 received vehicle (n = 5), while group 2 was given vehicle + heparin (n = 6; 500 U bolus + 350 U/h). This dose of heparin increased the activated partial thromboplastin time (APTT) by at least 1.5 times the control level for the 4 h observation period. Group 3 received r-proUK alone at a dose of 100,000 U/kg (50% given as a 1-min bolus injection, 50% as a 30 min infusion) (n = 8), while group 4 was treated with the same dose of r-proUK in the presence of heparin as described (n = 8). Clot lysis at 4 h in groups 1 and 2 was 26 ± 3% and 28 ± 5%, respectively; flow was not restored in either group. In group 3, clot lysis was 50 ± 4% while group 4 showed lysis of 85 ± 5% (p <0.05). However, flow was not restored in any dog in group 3, while five of eight dogs in group 4 showed complete restoration of blood flow. In the remaining three dogs, flow was restored to 70–91% of control levels. The data suggest that a regimen of heparin pretreatment with continued infusion markedly increases the efficacy of r-proUK in this model and results in significant restoration of blood flow.

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Section: Discussionmentioning

confidence: 99%