Tissue Inflammatory Markers and Oxidative Stress in Swine Subjected to a 40% TBSA Burn Injury

Abstract

Burn injury is well known to induce a robust inflammatory response and hypermetabolic state. Intravenous (IV) crystalloid fluid resuscitation of burn patients is the foundation of modern burn care to improve tissue perfusion and outcomes. However, under military scenarios of far‐forward burn care or under civilian mass casualty situations, the availability of large volumes of such fluids for IV burn resuscitation will be logistically challenging and definitive burn care may be delayed for days. More recently, enteral resuscitation of burns has received renewed attention and some evidence suggests that it may reduce IV fluid requirements to support urine output. The present study investigated the early response of tissue inflammatory markers and evidence for oxidative stress in swine subjected to a 40% burn and resuscitated with enteral fluids compared to no fluids or a standard of care IV fluid regimen. Anesthetized Yorkshire swine (n=6 per group) were subjected to a 40% full thickness total body surface area (TBSA) burn with brass probes heated to 100°C. They were then randomized to 4 groups: 1) no fluid (NF), 2) 15 ml/kg/d WHO oral rehydration solution (ORS) (15‐ORS), 3) 70 ml/kg ORS (70‐ORS) or 4) 2 ml/kg/% burn IV lactated Ringer's (Modified Brooke (MB) formula‐ a standard of care). After 48 h, animals were euthanized and heart, liver, kidney, lung and small intestine collected and analyzed for tissue cytokine levels and indices of oxidative stress. As expected, urine output was higher in the 70‐ORS and MB groups than the NF group (p<0.01). Although plasma creatinine and BUN peaked 6 h after burn, levels returned to baseline by 48 h in all groups except 15‐ORS and NF. In the kidney, levels of IL‐1β, IL‐6 and TNF‐α tended to be higher in the 70‐ORS and MB groups, whereas IL‐10 levels were similar among groups. In liver, heart and jejunum, only IL‐1β levels tended to be higher in MB than the other groups, with a similar trend in IL‐10 concentrations. With regard to oxidant status in kidney, total antioxidant levels, glutathione reductase (GR) and glutathione peroxidase activities were higher in 70‐ORS than the other groups. Mn‐superoxide dismutase (SOD) activity was higher in both 70‐ORS and MB groups, with no differences in catalase activity or nitric oxide levels. In liver, the lowest levels of total antioxidants, SOD, GR and catalase activities were observed in the NF groups compared to the others. No significant differences in indices of antioxidant status were observed in jejunum, heart or lung among groups. Typically, these variables in 15‐ORS were similar to the NF group in all tissues. The results of this study indicate that enteral fluids may be as effective as a standard of care IV fluid regimen in maintaining antioxidant status in vital organs without major changes in pro‐inflammatory cytokines. As such, this oral resuscitation may prove lifesaving in resource poor environments and reduce potential IVfluid‐related complications until definitive clinical care is available.Support or Funding InformationFunded by US Army MRMCThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.