Pathogenic effects of monocytopenia, granulocytopenia and dexamethasone on the course of experimental Pseudomonas aeruginosa endocarditis in rabbits.
Intravegetation host inflammatory cell function may play a role in the more salutary clinical outcomes in human right- vs. left-sided endocarditis. To study this in vivo, 90 rabbits with tricuspid Pseudomonas aeruginosa endocarditis received either no therapy (controls), nitrogen mustard (HN2) to induce combined granulocytopenia + monocytopenia, etoposide (VP-16-213) to induce selective monocytopenia, or dexamethasone. Intravegetation inflammatory cell influxes were scored on a semiquantitative histopathologic scale. In VP-16-213 and dexamethasone recipients and tricuspid endocarditis controls, gradual decreases in mean intravegetation bacterial densities were observed over a 13-day infection period; in contrast, HN2 treatment was associated with a significant increase in intravegetation bacterial densities by day 13 of infection (p less than 0.001 vs. other tricuspid endocarditis groups). Histopathologically, vegetations from untreated controls and dexamethasone recipients showed granulocyte influxes during infection, while HN2 treatment resulted in predominantly granulocyte depletion within infected tricuspid vegetations; VP-16-213 caused mononuclear cell depletion at this site. This study supports the concept that the granulocyte plays a critical role in modulating spontaneous endocardial clearances of bacteria in experimental tricuspid endocarditis.
Bayer
A S
AS
Department of Medicine, Harbor-UCLA Medical Center, Torrance.
Yih
J
J
Chiu
C Y
CY
Nast
C C
CC
D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology*; D004697:Endocarditis, Bacterial / Q000276:immunology* / Q000473:pathology; D005047:Etoposide / Q000494:pharmacology; D006098:Granulocytes / Q000502:physiology*; D007958:Leukocyte Count; D008466:Mechlorethamine / Q000494:pharmacology; D009000:Monocytes / Q000502:physiology*; D011552:Pseudomonas Infections / Q000276:immunology* / Q000473:pathology; D011550:Pseudomonas aeruginosa / Q000302:isolation & purification; D011817:Rabbits
D008466:Mechlorethamine; D005047:Etoposide; D003907:Dexamethasone