Therapeutic Advantage of Recombinant Human Plasminogen Activator in Endocarditis: Evidence from Experiments in Rabbits

Abstract

SummaryIn infective endocarditis vegetations are stabilized by fibrin. To learn if fibrin digestion would be therapeutic, experimental endocarditis was induced in rabbits by inoculation with a platelet-aggregating strain (Agg+) of Streptococcus sanguis and treated with recombinant tissue plasminogen activator (rt-PA), rt-PA with penicillin, or penicillin alone. Control rabbits were inoculated with saline. All treatments of Agg+ 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 penicillin 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 111Indium-labelled platelets from the heart than untreated rabbits and 1.4-fold more after 3 days. Combined with penicillin, thrombolytic therapy for human endocarditis should be reconsidered.