Optimizing the bolus/infusion ratio for intravenous administration of urokinase in dogs

The purpose of this study was to determine the optimal bolus/infusion ratio of urokinase (UK) in a dog model of experimental thrombosis. Radiolabelled clots from dog whole blood were inserted into an extra-corporeal jugular loop in anesthetized dogs. Clot size (counts/min) was continuously recorded. UK was administered i.v. as a 1 min bolus (100%/0%), 30 min infusion (0%/100%), or as a bolus/infusion combination at ratios of 75%/25%, 50%/50%, or 25%/75%. The total dose of UK in all groups was 20,000 U/kg. A bolus/infusion ratio of 25%/75% produced twice as much lysis as either bolus or infusion alone. There were no statistical differences between the UK-treated groups in reduction of plasma alpha₂-antiplasmin concentration. We conclude that thrombolytic efficacy was increased by the bolus/infusion administration of UK without a concomitant increase in systemic plasminogen to plasmin conversion.