Comparison of intravenous bolus injection or continuous infusion of
recombinant single chain urokinase-type plasminogen activator (saruplase)
for thrombolysis. A canine model of combined coronary arterial and femoral
venous thrombosis
HJ Rapold, ZM Wu, T Stassen, F Van de Werf and D Collen
Center for Thrombosis and Vascular Research, University of Leuven, Belgium.
The thrombolytic efficacy of recombinant unglycosylated full length single
chain urokinase-type plasminogen activator (rscu-PA, saruplase), applied
either as single intravenous bolus or as a continuous infusion over 60
minutes, was studied in 5 randomized blinded groups of 5 dogs with combined
copper coil induced coronary artery thrombosis and 125I- fibrin labeled
femoral vein clots. Infusion of 1 mg/kg recu-PA (group I) induced coronary
recanalization in 4 of 5 dogs and 98 +/- 1% (mean +/- SEM) venous clot
lysis. Bolus injection of 1 mg/kg recu-PA (group II) caused reflow in 3 of
5 dogs and 88 +/- 5 percent venous clot lysis. Infusion of 0.5 mg/kg
rescu-PA (group III) achieved reflow in 3 of 5 dogs and 52 +/- 6% venous
clot lysis. Bolus injection of 0.5 mg/kg rscu-PA (group IV) induced reflow
in 4 of 5 dogs and 48 +/- 12% venous clot lysis. Placebo infusion (group V)
was associated with late recanalization in 1 of 5 dogs and 18 +/- 8% venous
clot lysis. Coronary artery reocclusion after reflow was not observed in
groups I and II, but occurred in 2 of 3 animals in group III and in 3 of 4
animals in group IV (P = .02). The time to reflow in responsive animals was
22 +/- 5 minutes with infusion of 0.5 or 1 mg/kg rscu-PA and 14 +/- 1
minute with bolus injection of 0.5 or 1 mg/kg (P = .14). Depletion of
fibrinogen and alpha 2-antiplasmin to less than 25% of baseline levels was
observed in the 5 dogs given 1 mg/kg rscu-PA by bolus and in 3 of the 5
dogs given 1 mg/kg rscu-PA via infusion, but in none of the dogs that
received 0.5 mg/kg rscu-PA (P less than .001). Plasma clearance rates were
170 +/- 44 and 230 +/- 30 mL/minute after bolus injection and 190 +/- 47
and 310 +/- 56 mL/minute during infusion of rscu-PA for the 1 mg/kg and 0.5
mg/kg doses respectively. Thus, intravenous bolus injection of rscu-PA
(saruplase) appears to be equipotent to an infusion over 60 minutes for
both coronary and venous thrombolysis. This animal model of combined
arterial and venous thrombolysis may be useful for the evaluation of new
thrombolytic strategies.
Volume 76,
Issue 8,
pp. 1558-1563,
10/15/1990
Copyright © 1990 by The American Society of Hematology
