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Burn injury exacerbates hemodynamic and metabolic responses in rats with polymicrobial sepsis
Masakatsu Goto1, Victoria Samonte, Thyyar Ravindranath
1Department of Surgery, Burn and Shock Trauma Institute, Loyola University Medical Center, Maywood, Illinois, USA.
Abstract:
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 PMN activation.
Insights
Severe burn injury combined with infection significantly increases polymorphonuclear neutrophil (PMN) activation, leading to severe microvascular damage and high mortality from multiple organ failure (MOF). This highlights PMN
Area of Science:
- Biomedical Sciences
- Immunology
- Trauma Research
Background:
- Infection is a major cause of mortality following severe burn injuries, often leading to multiple organ failure (MOF).
- The precise mechanisms linking burn injury, infection, and MOF remain incompletely understood.
- Previous research suggests polymorphonuclear neutrophils (PMNs) play a critical role in burn-induced microvascular leakage.
Purpose of the Study:
- To investigate the combined effects of burn injury and polymicrobial infection on PMN activation, microvascular permeability, and systemic hemodynamics and metabolism.
- To determine if the combination of burn and infection exacerbates MOF more than either insult alone.
- To elucidate the role of PMN activation in the high mortality observed in burn-infected patients.
Main Methods:
- Utilizing a rat model, researchers compared four groups: sham, burn injury only, cecal ligation and puncture (CLP) infection only, and combined burn and CLP.
- Assessed microvascular permeability to albumin, myeloperoxidase activity, and PMN-derived elastase and reactive oxygen species production.
- Monitored hemodynamic and metabolic parameters and recorded mortality rates.
Main Results:
- The combined burn and infection group exhibited significantly higher increases in microvascular permeability, myeloperoxidase activity, and PMN activation markers compared to burn or infection alone.
- Persistent polymicrobial bacteremia was observed in the burn+CLP group.
- Mortality was significantly elevated in the burn+CLP group (79%) compared to the burn (low) or CLP (low) groups.
Conclusions:
- The combination of severe burn injury and polymicrobial infection leads to uncontrolled PMN activation and severe microvascular damage.
- This exacerbated inflammatory response and microvascular injury mediated by PMNs is a likely mechanism driving the high incidence of multiple organ failure and mortality.
- Targeting PMN activation may be a crucial therapeutic strategy for managing severe burn injuries complicated by infection.
