doi: 10.1161/hc0602.103721
(Circulation. 2002;105:746.)
© 2002 American Heart Association, Inc.
Basic Science Reports |
In Vitro Susceptibility to Thrombin-Induced Platelet Microbicidal Protein Is Associated With Reduced Disease Progression and Complication Rates in Experimental Staphylococcus aureus Endocarditis
Microbiological, Histopathologic, and Echocardiographic Analyses
From the Division of Infectious Diseases (L.I.K., M.R.Y., A.S.B.), St John’s Cardiovascular Research Center and the Research & Education Institute, Harbor-UCLA Medical Center, Torrance, Calif; UCLA School of Medicine (M.R.Y., C.C.N., A.S.B.), Los Angeles, Calif; Division of Cardiology (S.M.S.), Department of Medicine, University of Southern California School of Medicine, Los Angeles, Calif; Department of Pathology (C.C.N.), Cedars-Sinai Medical Center, Los Angeles, Calif; and St Mary Medical Center (L.I.K.), Long Beach, Calif.
Correspondence to Leon Iri Kupferwasser, MD, Harbor-UCLA Medical Center, Research and Education Institute, Bldg RB-2, 1124 W Carson St, Torrance, CA 90502. E-mail kupferwasser{at}hotmail.com
Background— Mammalian platelets contain small, cationic, staphylocidal peptides, termed thrombin-induced platelet-microbicidal proteins (tPMPs). Evidence suggests that tPMPs play a key role in host defense against endovascular infections, such as infective endocarditis (IE). In the present study, we evaluated the influence of differences in staphylococcal tPMP-susceptibility profiles in vitro on disease severity in experimental IE.
Methods and Results— Experimental IE was induced in rabbits with either a tPMP-susceptible or an isogenic tPMP-resistant Staphylococcus aureus strain. Vegetation size, left ventricular fractional shortening, and onset of aortic valvular regurgitation were serially assessed by echocardiography over an 11-day postinfection period. In addition, blood cultures were performed daily. Parameters delineated at autopsy included vegetation weights; bacterial densities in vegetations, myocardium, and kidneys; extent of valvular and perivalvular tissue damage; and renal embolization. The following significant differences were observed in animals infected with the tPMP-susceptible versus the tPMP-resistant S aureus strain: substantially lower bacteremia rates (P=0.02); reduced vegetation growth (P<0.001) and weight (P<0.001); a later onset of aortic valvular regurgitation (P=0.0039); increased preservation of left ventricular function (P<0.001); reduced valvular tissue damage (P=0.01) and perivalvular inflammation (P=0.015); and reduced bacterial densities in vegetations (P<0.001) and kidneys (P<0.01).
Conclusions— The in vitro tPMP-susceptibility profile in S aureus substantially affects a number of well-defined cardiac and microbiological parameters related to disease severity and prognosis in IE. These findings underscore the likelihood that platelets mitigate the pathogenesis of endovascular infections via local secretion of antimicrobial peptides.
Key Words: endocarditis • platelets • peptides
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