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

Abstract

In order to examine the biological activity of low-dose and continuously infused superantigen, and to establish a superantigen-induced multiple organ dysfunction animal model, several pathophysiological parameters were sequentially monitored in a toxin-concentration-controlled pig model. Anesthetized, mechanically ventilated and Swan-Ganz thermodilution catheter-inserted pigs were treated with toxic shock syndrome toxin-1 (TSST-1) by infusion at 2 microg/kg/h for 5 h. Monitoring was performed for both the infusion period and a subsequent 1-h post-infusion period. The serum concentration of TSST-1 was controlled so as to elevate it to a level over 1000 pg/mL within 1 h of initiation of infusion, and then gradually increased further and reached a plateau of about 2500 pg/mL at 4h after initiation. The animals showed a significant increase in cardiac output, the intrapulmonary arteriovenous shunt ratio, and infiltration of white blood cells into the lung. Although the observed increase in pulmonary vascular resistance was not statistically significant, it did correlate with the reduction in white blood cell counts. 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.