INDUCIBLE CARBOXYPEPTIDASE ACTIVITY - A ROLE IN CLOT LYSIS IN-VIVO

Background An inducible carboxypeptidase activity in human plasma dela ys tissue-type plasminogen activator (TPA)-induced clot lysis in vitro . We investigated whether carboxypeptidase activity is induced in vivo during thrombosis and thrombolytic therapy in a canine model of myoca rdial infarction. Methods and Results By use of synthetic substrate as says, dog plasma was shown to contain an inducible carboxypeptidase ac tivity that is efficiently inhibited by potato carboxypeptidase inhibi tor. This inhibitor accelerates TPA-mediated clot lysis in vitro by an average of 27% (n=5, P=.046). Analysis of the inducible carboxypeptid ase activity in plasma samples of dogs with electrically induced throm bosis of the circumflex coronary artery treated with TPA revealed that (1) inducible carboxypeptidase activity is increased during thrombosi s (8.7+/-2.0 U/L, P<.013) ani thrombolytic therapy (9.9+/-1.8 U/L, P<. 024) compared with baseline (3.2+/-2.0 U/L); (2) thrombosis is a prere quisite of carboxypeptidase induction during and after TPA infusion, s ince carboxypeptidase levels were lower in clogs without a coronary th rombus; and (3) a significant positive correlation (r=.6, P<.0069) of carboxypeptidase activity with time to restoration of blood flow was o bserved. Conclusions These data indicate that carboxypeptidase activit y is induced in vivo and may influence thrombolysis.