Fig 8. Experimental modeling of the natural history of systemic responses to infection.

A “high-fidelity” longitudinal swine model of infection induced by injection of pathogenic E. coli into the kidney parenchyma leads to numerous events including but not limited to fever, altered clinical chemistries, increases in blood inflammatory cytokines, alterations in hematologic and immune cell numbers, disruption in metabolism and ultimately, loss of hemodynamic stability. These events culminate as end-organ dysfunction and injury. This model permits the measurement of numerous parameters as infection progresses which allows for the detailed study of key features that lead to, and mechanisms that underlie, organ dysfunction and failure. It also allows for the manipulation of host factors such as sex, age and diet. Improved understanding of the temporal relationship of these events will help drive well-informed testing of intervention strategies including fluid resuscitation and targeted therapeutics.