INTRAVENOUS THROMBOLYSIS WITH RECOMBINANT STAPHYLOKINASE VERSUS TISSUE-TYPE PLASMINOGEN-ACTIVATOR IN A RABBIT EMBOLIC STROKE MODEL

Background and Purpose Timely intravenous administration of recombinan t tissue-type plasminogen activator (alteplase, rTPA) to patients with evolving ischemic stroke improves neurological outcome. The present s tudy was designed to compare the effects of rTPA and recombinant staph ylokinase (Sak), a highly fibrin-specific thrombolytic agent, in an ex perimental model of rabbit embolic stroke. Methods Groups of 5 to 12 r abbits were given intravenous saline or heparin and aspirin with, in a ddition, either Sak (1 or 2 mg/kg infused over 30 minutes or 2 mg/kg i njected over 1 minute) or rTPA (3 or 6 mg/kg infused over 30 minutes o r 6 mg/kg injected over 1 minute). Infusions were started 15 minutes a fter selective injection of standardized I-125-fibrin labeled rabbit p lasma clots into the internal carotid artery. Results Mean clot lysis over 60 minutes increased from 3.8% after saline to between 27% and 44 % after Sak regimens (P=.0001 versus control) and to between 15% and 3 4% after rTPA regimens (P=.0001). Median volume of the ischemic lesion at 5 hours decreased from 190 mm(3) after saline to between 11 and 17 mm(3) after Sak (P=.02) and to between 0.5 to 54 mm(3) after rTPA (P= .04). Mean neurological impairment at 5 hours (on a scale of 0 to 3) d ecreased from 2.3 after saline to between 1.3 to 1.6 after Sak (P=.003 ) and to between 1.1 to 1.9 after rTPA (P=.02). At the highest doses u sed, fibrinogen depletion was marginal with Sak but total with rTPA. M arked prolongation of ear puncture and cuticle bleeding times was only observed after bolus administration of rTPA. Conclusions In the prese nt rabbit model of embolic stroke, Sak was significantly more fibrin-s pecific than rTPA and at least as effective in lysing arterial emboli and limiting ischemia and neurological impairment.