THERAPEUTIC ADVANTAGE OF RECOMBINANT HUMAN PLASMINOGEN-ACTIVATOR IN ENDOCARDITIS - EVIDENCE FROM EXPERIMENTS IN RABBITS

In infective endocarditis vegetations an stabilized by fibrin. To lear n if fibrin digestion would be therapeutic, experimental endocarditis was induced in rabbits by inoculation with a platelet-aggreating strai n (Agg+) of Streptococcus sanguis and treated with recombinant tissue plasminogen activator (rt-PA), rt-PA with penicillin, or penicillin al one. Control rabbits were inoculated with saline. All treatments of Ag g+ endocarditis reduced the mass of valvular vegetations and clinical signs of endocarditis, including the frequency of left axis deviation and heart ischemia. rt-PA with penicillin was more effective than peni cillin or rt-PA alone, reducing the mass of vegetations and clinical signs to that of saline controls. Within 50 min, rt-PA cleared 5-fold more (111)Indium-labelled platelets from the heart than untreated rabb its and 1.4-fold more after 3 days. Combined with penicillin, thrombol ytic therapy for human endocarditis should be reconsidered.