The pathogenesis of infective endocarditis.

Three aspects of our current understanding of the pathogenesis of infective endocarditis are reviewed: the size of the infected vegetation, host defence mechanisms and conditions which determine the outcome of experimental infection. Animal studies have been conducted with anticoagulants in which fatal infective endocarditis was produced without macroscopic evidence of endocardial vegetations. Detection of such lesions in man would change our perception of the epidemiology and clinical course of the disorder. It is probable that polymorphonuclear leucocytes are important in limiting the development of infected vegetations throughout the vascular system and, because of their ineffectiveness in the left side of the heart, are probably responsible for the preponderance of infections within that particular part of the circulation. Furthermore, polymorphonuclear leucocytes may also contribute to the pathogenesis of valve perforation. Finally, the size of the bacterial challenge, and the duration of catheterization of the heart to induce infection, have been shown to significantly influence the natural history of experimental infection and also the effectiveness of prophylactic antibiotics. Any comparison of the effectiveness of different prophylactic measures will require careful standardization of these conditions. It is difficult to determine the optimal size of the bacterial inoculum in animal studies since so little is known about this factor in man. Peripheral infections in animals may disseminate sufficient bacteria to produce endocardial infection and yet not be easily, if at all, detectable in the circulating blood.