Thrombolytic efficacy of recombinant tissue plasminogen activators in rabbits with experimental juglar vein thrombosis.
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The thrombolytic efficacy of plasminogen activators (PAs) were compared using juglar vein thrombus model of rabbits (Collen et al. J. Clin. Invest. 71, 368-376, 1983). PAs were one-chain, two-chain and the mixure of both chains of recombinant tissue PAs (one-, two- and m-rTPAs) and high molecular weight of urokinase (UK). The thrombus was formed using 125I-labeled human fibrinogen. The thrombolytic ratio was calculated by the radioactivities of thrombus, circulating blood, washing water surround the thrombus and the catheter used for washing out the free radioactivity in the external juglar vein ligated at the time of thrombus formation. The levels of PAs were measured by Labeled Avidin-Biotin technique using anti-TPA polyclonal antibody and bioninated anti-TPA antibody. The levels of blood elements concerning with thrombolysis were also measured at two hours intervals.1. The thrombi were dissolved dose-dependently from 0.055 to 0.2mg/kg body weight of m-rTPA and the mamimum thrombolytic ratio was calculated 72±9% (n=5). The maximum ratio of one- and two-rTPAs was the same value of m-rTPA. The concentration of these rTPAs was considered around 0.4mg/kg at the maximum ratio. On the other hand, the maximum thrombolytic ratio using by UK was remained around 43±11% (n=6) and needed concentration of UK to obtained the maximum ratio was around 2mg/kg.2. The levels of fibrinogen, plasminogen and α2-plasmin inhibitor in circulating blood were not decreased using rTPAs, but decreased using UK dose-dependently. No significant difference of these parameters was recognized among the differences of rTPAs employed.3. 10% of total volume of rTPAs were administered as a bolus injection and the residual 90% were administered as continuous infusion over 4 hours and the levels were measured. Although it was found a tendency that the level of one-rTPA in plasma was higher than that of two-rTPA, the difference was not significant statistically.It was concluded that rTPAs appears to be superior to UK, because of its higher (over 10 fold) specific thrombolytic efficacy than that of UK. In this thrombus model experiment using rabbits, no difference was found in thrombolitic efficacy and effect on coagulation parameters in plasma among three different rTPAs.
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