Effect of nitrogen mustard on natural history of right-sided streptococcal endocarditis in rabbits: role for cellular host defenses

Abstract

Cellular host defenses are considered to be ineffective in bacterial endocarditis; the microorganisms in infected vegetations are protected from phagocytic cells by dense layers of fibrin. To test this hypothesis, nitrogen mustard-induced agranulocytosis and leukopenia were produced in rabbits with right-sided streptococcal endocarditis. The spontaneous sterilization of tricuspid infection observed in the control animals was not present in the granulocytopenic, leukopenic animals. Since the bacterium Streptococcus intermedius is not sensitive to the complement-mediated bactericidal effect of serum and since the animals were not bacteremic during the time of agranulocytosis, an inhibitory effect of the drug on local cellular host defense mechanisms is postulated. We suggest that the spontaneous sterilization of infective endocarditis in the right side of the heart in rabbits is mediated by cellular host defenses.

Enhancement of experimental bacteremia and endocarditis caused by dysgonic fermenter (DF-2) bacterium after treatment with methylprednisolone and after splenectomy

“…This structure is different from that of gram-negative coccal infections described by Durack (7), in which clusters of bacteria were usually separated from inflammatory cells by strands of fibrin. Our finding of polymorphonuclear leukocytes near bacteria in the vegetations is more consistent with the results of Meddens et al (20) and Yersin et al (28), who found that with streptococcal endocarditis, polymorphonuclear leukocytes were numerous in the vegetations.…”

“…Experiments to immunosuppress rabbits before infection with the DF-2 bacterium were undertaken because of the relatively weak pathogenecity of this organism and the association of human DF-2 infection with immunosuppression (5). Other workers have reported results with the catheterized rabbit model of endocarditis and treatment with nitrogen mustard (20,28) and with dexamethasone (11). Meddens et al (20) showed that, by depleting leukocytes, nitrogen mustard caused a higher density of streptococcal bacteria in rabbits with left-side cardiac vegetations than in control rabbits, but the infective dose of bacteria in treated rabbits was not changed.…”

Effects of alginase on the natural history and antibiotic therapy of experimental endocarditis caused by mucoid Pseudomonas aeruginosa

“…The current study was designed to examine the functional role of alginate in an experimental animal model system of invasive pseudomonal infection (endocarditis). In animals with right-sided endocarditis, we examined the role of alginate in interfering with PMN-mediated clearance of mucoid P. aeruginosa from cardiac vegetations (7,29); in animals with left-sided endocarditis, the role of alginate in interfering with antibiotic-mediated bacterial clearances was investigated. In both studies, an alginate depolymerase enzyme (alginase) was utilized in vivo in an attempt to enhance both 3980 BAYER ET AL.…”

Exopolysaccharide production by viridans streptococci in experimental endocarditis

“…A possible role for in vivo glycocalyx production in the maintenance of infection is suggested by the fact that vegetations formed by organisms producing large amounts of glycocalyx were larger than those produced by glycocalyxdeficient bacteria. Large vegetations would be more resistant to host defense mechanisms (leukocytes, antibody, and complement) than small ones (32). Large vegetations would be more likely to embolize than small ones, and large vegetations are also likely to be more difficult to sterilize by antimicrobial agents (14).…”