Burn injury exacerbates hemodynamic and metabolic responses in rats with polymicrobial sepsis.

The most common and life-threatening complication of severe burn injury is infection, which often results in multiple organ failure (MOF). However, the mechanism of development of MOF after burn injury associated with infection is not fully understood. Our previous studies showed that when polymorphonuclear neutrophils (PMNs) are depleted, burn injury-induced increase in microvascular permeability to albumin is markedly attenuated. Thus, we hypothesized that the combination of burn injury and polymicrobial infection exacerbates PMN activation, increases intestinal microvascular permeability to albumin, and alters hemodynamics and metabolism more than burn injury or infection alone. Sprague-Dawley rats (250-275 g) were divided into four groups. In the burn group, rats were subjected to a 30% TBSA burn injury. In the cecal-ligation puncture (CLP) group, CLP was performed using a 22-gauge needle with one puncture. In burn + CLP group, rats were subjected to CLP immediately after burn procedure. In sham group, rats were subjected to sham procedures. Transient polymicrobial bacteremia and persistent polymicrobial bacteremia were induced in the CLP group and burn + CLP group, respectively. Microvascular permeability, myeloperoxidase, and PMN production of elastase and reactive oxygen species increased in the burn group and CLP group and further increased in the burn + CLP group. Hemodunamic and metabolic alterations on day 1 and 3 after injury correlated with those alterations. Although there was only a low mortality in the burn group and CLP group, there was a high mortality in burn + CLP group (79%). The mechanism of MOF that leads to high mortality in burn injury complicated by infection may involve uncontrolled microvascular damage mediated by PAIN activation.