Stabilized procedure for the determination of urokinase fibrinolytic potency

Sutherland, Jerry W.; Banick, Donald W.; Schmakel, Conrad O.

doi:10.1016/0003-2697(91)90158-p

Cited by 7 publications

(2 citation statements)

References 18 publications

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“…The r-proUK was shown by tryptic mapping to have an identical protein sequence to that of natural proUK obtained from human kidney cells. After complete activation with human plasmin, the r-proUK had a specific activity of 165,000 IU/mg when rated by viscometric clot lysis assay (Ploug) against the World Health Organization international standard for urokinase (21). Chromogenic assay of the product showed that it contained less than 0.5% active two-chain urokinase prior to plasmin activation.…”

Section: Pro-urokinasementioning

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: Pro-urokinasementioning

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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“…Recombinant pro-urokinase at one regimen per dog and the vehicle (2.9 mglml NaC1, 30 mglml mannitol, 3.8 mglml citric acid, pH = 5) were studied in 6 groups of animals. The potential lytic activity of r-proUK was determined by a viscometric Plough assay (21). After treatment with plasmin to completely convert r-proUK to its 2-chain counterpart.…”

Section: Treatzent Groups and Dosing Regnnerzsmentioning

confidence: 99%

Comparison of Dose Regimens for the Administration of Recombinant Pro-urokinase in a Canine Thrombosis Model

et al. 1997

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SummaryPro-urokinase represents an important addition to the array of thrombolytic drugs currently available for clinical use because of its high clot specificity but distinctly different mechanism compared with that of t-PA. Recombinant pro-urokinase (r-proUK) is a single-chain precursor of high molecular weight urokinase which has been expressed in a mouse myeloma cell line. The present study was conducted to determine the dosing regimen which would produce optimal clot lysis and restoration of blood flow 2 h after treatment with r-proUK, using a dog model of arterial thrombosis. Efficacy was indicated by lysis of a radiolabelled clot which was formed in the heat-damaged femoral arteries of 39 male beagle dogs. The animals were divided into six heparinized treatment groups, each receiving one of five dosing regimens or the vehicle for r-proUK. The total dose (80,000 U/kg) was divided into an initial loading bolus, followed by either a second bolus or by infusions for various time periods, as shown below:It was concluded that optimal clot lysis and restoration of femoral flow was accomplished using a regimen in which 50% of the dose was given as a bolus, followed immediately by the remaining 50% given as a 30 min intravenous infusion (Group 5). At the dose used in this study, r-proUK did not produce degradation of fibrinolytic or hemostatic plasma proteins.

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Differential Effects of Lys- And Mini-Plasminogen on Clot Lysis Induced by Recombinant Urokinase and Recombinant Pro-Urokinase in a Canine Thrombosis Model

Burke¹,

Davidson²,

Lubbers³

et al. 1996

Thrombosis Research

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Stabilized procedure for the determination of urokinase fibrinolytic potency

Cited by 7 publications

References 18 publications

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

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

Comparison of Dose Regimens for the Administration of Recombinant Pro-urokinase in a Canine Thrombosis Model

Differential Effects of Lys- And Mini-Plasminogen on Clot Lysis Induced by Recombinant Urokinase and Recombinant Pro-Urokinase in a Canine Thrombosis Model

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