Synthesis of PAF-acether and blood volume changes in gram-negative sepsis

Gram-negative sepsis was induced in rats by intraperitoneal injection of Escherichia coli. The development of bacterial peritonitis and septicemia was monitored by counting the number of peritoneal cells and by performing cultures of blood samples. Mortality reached a 50% rate when rats were injected with 2 X 10(8) colony-forming units. Rats injected with the doses of bacteria which induced mortality showed a time- and dose-dependent increase of vascular permeability as judged by the presence of abundant peritoneal exudate and by the depletion of the circulating volume. In order to know whether the generation of PAF-acether could be involved in the development of the permeability changes, the formation of this mediator was measured in the peritoneal cells and spleen of animals at different times and in response to different doses of E. coli. Significant amounts of PAF-acether could be obtained preceding the development of blood volume depletion in response to the injection of doses of E. coli which induced both mortality and the development of permeability. These data suggest that PAF-acether might be one of the inflammatory mediators involved in the pathogenesis of the hemodynamic changes observed in endotoxemia.