Summary
Heparin 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.
