Enhanced lytic efficacy of multiple bolus injections of tissue plasminogen activator in dogs

The purpose of this study was to compare the lytic efficacy of tissue plasminogen activator (tPA) following different dosing regimens. Radiolabelled clots from dog whole blood were inserted into an extracorporeal jugular loop in anesthetized dogs. Clot size (counts/min) was continuously recorded, tPA was administered as a single 1 min bolus of 0.4 mg/kg, as four multiple bolus injections of 0.1 mg/kg each at 30 min intervals, or as an initial bolus (0.04 mg/kg) followed by a 30 min infusion of 0.36 mg/kg (10%/90%, bolus/infusion). Multiple injections of the same total dose of tPA resulted in 76% and 51% greater clot lysis than single bolus injection or bolus/infusion regimen, respectively, measured 120 min after initial dosing. There were no differences in fibrinogen, plasminogen or alpha-2-antiplasmin between the different treatment groups at 120 min.