Hyperdynamic sepsis in baboons: II. Relation of organ damage to severity of sepsis evaluated by a newly developed...

The purpose of our study was to set up a baboon hyperdynamic sepsis model with live bacteria administration, which produces within 8 hr an organ failure comparable to human pathological conditions. Twelve adult male baboons were instrumented and studied for 8 hr under pentobarbital (2-3 mg/kg BW/hr) anesthesia breathing spontaneously. The animals were divided into two groups: 1) Live Escherichia coli were infused intravenously at a dose of 1.0-2.0 x 10(10) CFU/kg BW over 8 hr; 2) Live E. coli were infused i.v. at a dose of 5 x 10(8) CFU/kg BW over 2 hr. Organ damage was monitored by a newly developed scoring system. Organ damage was clearly dependent on the concentration of the bacterial challenge. Bacterial challenge at a dosage of 5.0 x 10(8) produces insignificant hemodynamic effects, while the 1.0-2.0 x 10(10) animals demonstrated massive hemodynamic alterations and needed much higher fluid support. The higher E. coli dosage was associated with an overwhelming organ damage seen, e.g., from the lung weight (12 g/kg BW vs. 9.6 g/kg BW with the lower dosage) or from the organ failure score, which is based on macroscopic pathology, histological data and organ weight. The percentage of animals with one, two, or three organ failures (organ failure score > or = 2) was higher in baboons with the higher dosage/kg BW. Therefore, we believe that the less severe organ damage in the acute phase after 8 hr with live bacteria 5 x 10(8) CFU/kg BW infusion over 2 hr is better to monitor the efficacy of newly developed therapeutic regimens, since in another set of experiments this model still produces lethal organ damage (80%) in a subchronic setting over 72 hr.