CORONARY THROMBOLYSIS WITH DESMODUS SALIVARY PLASMINOGEN-ACTIVATOR INDOGS - FAST AND PERSISTENT RECANALIZATION BY INTRAVENOUS BOLUS ADMINISTRATION

Background DSPA (Desmodus salivary plasminogen activator) is a new thr ombolytic agent corresponding to a natural plasminogen activator disco vered in the saliva of the vampire bat Desmodus rotundus. Compared wit h tissue plasminogen activator (TPA), DSPA, produced in a recombinant cell line, is more fibrin cofactor dependent than TPA. Methods and Res ults The thrombolytic properties of DSPA and TPA were compared in a ca nine model of copper coil-induced coronary thrombosis. Ah dogs receive d heparin 200 IU/kg IV and SC. Whereas controls did not reperfuse with in 180 minutes (none of six), intravenous bolus administration of DSPA at 25, 50, and 100 mu g/kg resulted in a 100% incidence (6 of 6) of r ecanalization within 37, 23, and 18 minutes, respectively. TPA at 63 a nd 125 mu g/kg reopened the coronaries in 33% (two of six) and 50% (th ree of six) of cases within 40 minutes. Eighty-three percent (5 of 6) of the arteries were still patent 3 hours after 50 and 100 mu g/kg DSP A, whereas only 20% (one of five) of all coronaries originally recanal ized with both doses of TPA were still open at 3 hours. Plasma levels of alpha(2)-antiplasmin decreased significantly only with 125 mu g/kg TPA. The clearance of DSPA (2.3 to 3.5 mL.min(-1).kg(-1)) was lower co mpared with TPA (11.4 to 20 mL.min(-1).kg(-1)) due to a prolonged term inal half-life. Conclusions In a canine coronary thrombosis model, DSP A exhibited higher potency and recanalized coronary arteries faster an d with a lower incidence of reocclusion than TPA. Its properties may t ranslate into a higher efficacy in patients compared with available th rombolytic agents. The long half-life of DSPA may allow for single bol us administration in the treatment of acute myocardial infarction.