Therapeutic advantage of recombinant human plasminogen activator in endocarditis: evidence from experiments in rabbits.
In 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.
D000818:Animals; D004195:Disease Models, Animal; D004338:Drug Combinations; D004696:Endocarditis / Q000188:drug therapy* / Q000382:microbiology; D006801:Humans; D010406:Penicillins / Q000008:administration & dosage; D010960:Plasminogen Activators / Q000008:administration & dosage / Q000627:therapeutic use*; D011817:Rabbits; D011994:Recombinant Proteins / Q000627:therapeutic use; D013290:Streptococcal Infections / Q000188:drug therapy; D013298:Streptococcus sanguis
D004338:Drug Combinations; D010406:Penicillins; D011994:Recombinant Proteins; D010960:Plasminogen Activators