Pseudomonas aeruginosa-infected dogs had markedly lower endotoxin levels compared with the E coli groups (p<0.0001). Eleven of 32 animals died in the P aeruginosa group compared with none of the nonirradiated E coli dogs (7 and 14 x 109 CFU/kg), despite circulating endotoxin concentrations that were more than tenfold lower in the P aeruginosa-infected dogs (Table 2). Other parameters (Table 3) also pointed to a pattern of greater severity of illness in the setting of relatively low levels of endotoxemia in P aeruginosa vs E coli groups. As shown, P aeruginosa (14 X 109 CFU/ kg) produced greater falls in MAP and LVEF (p<0.05) than E coli (7 X109 CFU/kg), despite the higher endotoxin concentrations produced by the latter.
This disparity between endotoxin concentrations and clinical end points in the P aeruginosa group could not be explained by additive toxicity from exotoxin A, a potent toxin thought to be important in Pseudomonas infections. The P aeruginosa strain used in these experiments released no detectable exotoxin A as measured by Western blot after overnight growth in high-yield media (Fig 4). Further, the endotoxin content per bacterium, as determined by LAL assay, was similar for the E coli and P aeruginosa used in this study, 25.5 fg/CFU and 26.6 fg/CFU, respectively (in equivalent weight of US standard endotoxin). buy ortho tri-cyclen online
As stated above, radiation-induced leukopenia increased mortality from 0 to 60 percent in E coli-infected dogs, but it did not affect the pattern or severity of the hemodynamic abnormalities (Fig 2 and 3, and Table 3). The increased mortality seen in irradiated, E coZt-infected dogs was not caused by higher concentrations of circulating endotoxin (Table 2), despite the marked immune suppression.
Table 3—Mean Decreases in Mean Arterial Pressure and Left Ventricular Ejection Fraction
|Study Group||Decrease in MAP, mm Hg||Decrease in LVEF|
|7X10°||— 24 ±6||— 0.16±0.03|
|14X10*||— 30 ±5||-0.27 ±0.03|
|14 x 10” (with radiation)||— 32 ±4||-0.25 ±0.02|
|2. P aeruginosa^||— 41 ±3||-0.24 ±0.02|
Figure 4. Western blot of supernatants from P aeruginosa stained for exotoxin A. P aeruginosa strain PA103, a known exotoxin A producer, is shown in lane 1. The dark band at a MW of approximately 71,000 represents intact monomeric exotoxin A (see purified exotoxin A standard in lane 4). Bands above and below this point represent exotoxin A aggregates and partially digested exotoxin A, respectively. Concentrated supernatant from the P aeruginosa strain used in this study was run in lanes 2 and 3. No exotoxin A was detected.
Category: Pseudomonas aeruginosa
Tags: aeruginosa, endotoxin, sepsis, septic shock