Superantigen-induced multiple organ dysfunction in a toxin-concentration-controlled and sequential parameter-monitored swine sepsis model

Abstract

The superantigen TSST-1 plays an important role in the pathogenesis of Gram-positive bacterial sepsis by inducing multiple organ dysfunction. Thus, this model provides the first tool to allow the simultaneous examination of the serum toxin levels and other organ parameters in a time-course manner.

Physiological Response to Superantigen-Adsorbing Hemoperfusion in Toxin-Concentration-Controlled Septic Swine

“…However, these animals are too small for the monitoring of several physiological parameters, and tox- in concentrations in the circulating blood cannot be controlled and maintained at clinical levels. To overcome these problems, we have developed a sepsis model in swine that is toxin concentration controlled and with which a Swan-Ganz catheter can be used sepsis model in swine [14] ; in addition, this model is not lethal. Laboratory animals are intrinsically resistant to the toxicity of SAg and require far higher doses of SAg than do humans to induce shock; for this reason, prior sensitization with D -galactosamine or co-administration with LPS are used to induce lethality in low-dose, SAg-administration animal models [4,8] .…”

“…In terms of these changes, Qs/Qt and PaO 2 were signifi cantly improved by SAAD treatment ( fi g. 2 ). We previously reported that TSST-1-induced infi ltration of WBC into the lung is one of the causes of respiratory failure, which is measured as the correlation between the decrease in WBC counts and increase in PVR [14] . In this study, a statistically signifi cant correlation was observed between the decrease in the WBC count and increase in the PVR, which indicates the infi ltration of WBC into the lung in individual animals for the entire 6-hour observation period in both the SAAD-treated and control groups.…”

“…The toxin-concentration-controlled sepsis model was developed in swine as previously reported [14] . Briefl y, swine were anesthetized by intramuscular administration of ketamine (17 mg/kg) and atropine sulfate (0.03 mg/kg) and maintained under anesthesia by mechanical ventilation with an oxygen-enriched air mixture containing 1% isofl urane [inspired oxygen fractional concentration (F i O 2 ) = 0.80] at a tidal volume of 10 ml/kg and a respiration rate of 15 strokes/min using a Servo Model 900D ventilator (SiemensElema, Stockholm, Sweden).…”

“…The cardiac and respiratory function parameters were monitored continuously for 10 h from the initiation of the TSST-1 continuous infusion; however, three animals (one in the SAAD-perfused group and two in the control group) had died before the 10-hours observation. For this reason, differences between the SAAD-treated and control groups were statistically analyzed at two time points: fi rst, at 6 h after the TSST-1 infusion was initiated (T6), the time point at which TSST-1-induced MODS were observed [14] ; then at 8 h after TSST-1 infusion was initiated (T8), the time point at which LPS infusion and hemoperfusion were completed. Another reason we chose T8 is that it was the fi nal time point at which all animals were alive and the numbers of swine between the two groups were equal.…”

“…Second, toxin concentration in the circulating blood could not be controlled enough to maintain it at previously reported clinical levels. To overcome these problems, we have developed a toxin-concentration-controlled multiple organ dysfunction syndrome (MODS) model in swine that allows frequent blood sampling and monitoring with a Swan-Ganz thermodilution catheter [14] . In this model, major complications in gram-positive bacterial infection have been observed, such as respiratory and cardiovascular dysfunction.…”