(Circulation. 1999;99:2791-2797.)
© 1999 American Heart Association, Inc.
Basic Science Reports |
Acetylsalicylic Acid Reduces Vegetation Bacterial Density, Hematogenous Bacterial Dissemination, and Frequency of Embolic Events in Experimental Staphylococcus aureus Endocarditis Through Antiplatelet and Antibacterial Effects
Presented in part at the 71st Scientific Sessions of the American Heart Association, Dallas, Tex, November 8–11, 1998, and published in abstract form (Circulation. 1998;98[suppl I]:I-700.)
From the Division of Adult Infectious Diseases (L.I.K., M.R.Y., S.G.F., A.S.B.) and Division of Cardiology (S.M.S.), St. John's Cardiovascular Research Center, Harbor–UCLA Medical Center, Torrance, Calif; UCLA School of Medicine (M.R.Y., S.M.S., S.G.F., A.S.B.), Los Angeles, Calif; Department of Pathology (C.C.N.), Cedars–Sinai Medical Center, Los Angeles, Calif; and Veterans Affairs Medical Center and University of California San Francisco (P.M.S.), San Francisco, Calif.
Correspondence to Leon Iri Kupferwasser, MD, Division of Infectious Diseases, LAC–Harbor UCLA Medical Center, 1000 W Carson St, Torrance, CA 90509 . E-mail kupferwasser{at}humc.edu
Background—Platelets are integral to cardiac vegetations that evolve in infectious endocarditis. It has been postulated that the antiplatelet aggregation effect of aspirin (ASA) might diminish vegetation evolution and embolic rates.
Methods and Results—Rabbits with Staphylococcus aureus endocarditis were given either no ASA (controls) or ASA at 4, 8, or 12 mg · kg-1 · d-1 IV for 3 days beginning 1 day after infection. Vegetation weights and serial echocardiographic vegetation size, vegetation and kidney bacterial densities, and extent of renal embolization were evaluated. In addition, the effect of ASA on early S aureus adherence to sterile vegetations was assessed. In vitro, bacterial adherence to platelets, fibrin matrices, or fibrin-platelet matrices was quantified with either platelets exposed to ASA or S aureus preexposed to salicylic acid (SAL). ASA at 8 mg · kg-1 · d-1 (but not at 4 or 12 mg · kg-1 · d-1) was associated with substantial decreases in vegetation weight (P<0.05), echocardiographic vegetation growth (P<0.001), vegetation (P<0.05) and renal bacterial densities and renal embolic lesions (P<0.05) versus controls. Diminished aggregation resulted when platelets were preexposed to ASA or when S aureus was preexposed to SAL (P<0.05). S aureus adherence to sterile vegetations (P<0.05) or to platelets in suspension (P<0.05), fibrin matrices (P<0.05), or fibrin-platelet matrices (P<0.05) was significantly reduced when bacteria were preexposed to SAL.
Conclusions—ASA reduces several principal indicators of severity and metastatic events in experimental S aureus endocarditis. These benefits involve ASA effects on both the platelet and the microbe.
Key Words: aspirin • embolism • endocarditis • platelets • fibrin
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