COMPARISON OF A BOLUS AND A INFUSION DOSE REGIMEN OF RECOMBINANT TISSUE TYPE PLASMINOGEN ACTIVATOR (rt-PA) ON THE RATE OF THROMBOLYSIS IN THE RABBIT JUGULAR VEIN MODEL (RJVM)

The success of intravenous infusion of rt-PA in the treatment of myocardial infarction, along with new applications in deep vein thrombosis and pulmonary embolism has stimulated interest in optimizing dosage regimens. Dosage strategies should be tested in a relevant animal model before clinical use. In the RJVM, net lysis is calculated frcm the difference in 1-125 fibrinogen present in a rabbit jugular vein thrombus, pre and post thrombolytic therapy, therefore changes in the rate of lysis would not be detected. To continuously monitor rates of lysis in the RJVM, a flat surface garrma detector probe was secured over the jugular vein thrombus of the anesthetized rabbit, and Gamma counts were accumulated for one minute, at 10 minute intervals. Rates of lysis and net lysis were calculated frcm these data. Net lysis was also determined by the traditional method in order to validate the new technique. Using this experimental design we compared the efficacy of a bolus (0.4 mg/kg over 1 min) to an infusion (0.4 mg/kg over 2 hours, 10% given as an initial bolus). A control group received an infusion of rt-PA excipient. The bolus group was terminated at 60 minutes, since there was no detectable lysis in any of these animals after 30 mins. There was an excellent correlation between the net lysis calculated either by the probe or the traditinal procedure (Y = 1.0 × −2.8, r = 0.88). The lysis rates were:

From these data we conclude that in the RJVM a bolus of rt-PA offers no clear advantage in efficacy over a comparable dose given as a 2 hr infusion. This observation appears to hold true even during the first 30 minutes of treatment where any advantage the bolus might have would most likely be evident