Potentiated thrombolysis in a Chandler system using rtPA and lys-plasminogen

The effect of glu/lys-plasminogen on rtPA induced thrombolysis was studied in a Chandler model using rabbit blood. Glu/lys-plasminogen in various concentrations was added to the Chandler loop before or after thrombi were formed from 2 ml of rabbit blood containing 125I-labelled rabbit fibrinogen. The thrombolysis was estimated as radioactivity in the supernatant/total radioactivity. Thrombi formed in the presence of extra lys-plasminogen (conc greater than or equal to 0.025 mg/ml blood) lysed spontaneously to a significantly higher extent than thrombi formed in the presence of glu-plasminogen or saline. If the glu/lys-plasminogen was added to a preformed thrombus no thrombolysis occurred. When added together with single-chain rtPA (s.c. rtPA) or two-chain rtPA (t.c.rtPA) the thrombolysis was similar to the one obtained by s.c./t.c.rtPA alone. If on the other hand s.c./t.c.rtPA was added to lys-plasminogen enriched thrombi (greater than 0.01 mg/ml blood) a significantly enhanced thrombolysis as compared to the one achieved by s.c./t.c.rtPA alone was obtained. Based on the observation that lys-plasminogen potentiates the lysis of thrombi in a Chandler model a bolus dose administered preoperatively may enhance spontaneous lysis of thrombi formed during surgery.