ROLE OF ENDOTOXEMIA IN CARDIOVASCULAR DYSFUNCTION AND LETHALITY - VIRULENT AND NONVIRULENT ESCHERICHIA-COLI CHALLENGES IN A CANINE MODEL OFSEPTIC SHOCK

We investigated whether the severity of septic shock is determined by virulence factors associated with or the levels of endotoxemia produce d by two Escherichia coli strains. Canines were challenged intraperito neally with an E. coli strain (06:H1:K-2) that has virulence factors a ssociated with human disease or with an equal dose of a nonvirulent st rain (086:H8) that lacks these factors. Both strains were administered in viable, heat-killed, and purified endotoxin forms. Median survival times with the virulent strain compared with the nonvirulent strain w ere shorter with viable bacteria (5 x 10(9) CFU/kg) (144 h versus >672 h; Wilcoxon, P = 0.03), longer with heat-killed bacteria (5 x 10(10) CFU/kg) (> 676 h versus 26 h; P = 0.03), and similar with purified end otoxin (15 mg/kg) (28 h versus 48 h; P = 0.71). However, whether the c hallenge contained viable bacteria, heat-killed bacteria, or purified endotoxin, the virulent strain produced less endotoxemia (P = 0.001). Hence, the changing outcomes with differing forms of the two strains c annot be attributed solely to endotoxin levels. The viable virulent st rain caused less endotoxemia but more harm, and this does not appear t o be explained by a more potent endotoxin or other heat-stable compone nt. This study suggests that circulating endotoxin levels per se are l ess important in the outcome of septic shock than virulence factors as sociated with E. coli strains. Furthermore, the data call into questio n the significance of the endotoxin concentration in the blood in pred icting the severity of shock and the lethality of gram-negative infect ions.