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Impact of burn priming on immune and metabolic functions of whole Liver in a rat cecal ligation and puncture model.

ABSTRACT: Previously, we have shown that systemic insults in single injury models produced immunosuppressive effects in burn, and a strong acute phase response in sepsis through hepatic gene expression. In order to investigate the implications of these effects on a combined injury, a double hit model was explored to mimic the progression of clinical burn-sepsis. Rodents were subjected to a 20% total body surface area (TSA) full-thickness burn injury, and 48 hours later underwent cecal ligation and puncture (CLP) to induce sepsis. Pathways related to innate immune signaling through cytokines and NF-KB were co regulated with xenobiotic metabolism genes and acute phase protein genes, and that these genes were suppressed early, and then activated. Furthermore, we were able to identify that, in addition to amino acid metabolism, pyruvate metabolism, fatty acid metabolism and NRF-2 mediated oxidative stress genes were down regulated over the time course. Overall, these observed trends within the double hit burn-sepsis model represent unique immune and metabolic pathways and dynamics not found in either injury, including an early suppression followed by overreaction of pro inflammatory mediators, and an increase in amino acid metabolism at the expense of central carbon pathways.

SUBMITTER: Mattick JS

PROVIDER: S-EPMC3560487 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Impact of burn priming on immune and metabolic functions of whole Liver in a rat cecal ligation and puncture model.

Mattick John Sa JS Yang Qian Q Orman Mehmet A MA Ierapetritou Marianthi G MG Berthiaume Francois F Gale Stephen C SC Androulakis Ioannis P IP

International journal of burns and trauma 20130124 1

Previously, we have shown that systemic insults in single injury models produced immunosuppressive effects in burn, and a strong acute phase response in sepsis through hepatic gene expression. In order to investigate the implications of these effects on a combined injury, a double hit model was explored to mimic the progression of clinical burn-sepsis. Rodents were subjected to a 20% total body surface area (TSA) full-thickness burn injury, and 48 hours later underwent cecal ligation and punctur ...[more]

PMID: 23386986

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Project description:BACKGROUND:The paradigm shift from crystalloid to plasma resuscitation of traumatic hemorrhagic shock has improved patient outcomes due in part to plasma-mediated reversal of catecholamine and inflammation-induced endothelial injury, decreasing vascular permeability and attenuating organ injury. Since sepsis induces a similar endothelial injury as seen in hemorrhage, we hypothesized that plasma resuscitation would increase 48-h survival in a rat sepsis model. METHODS:Adult male Sprague-Dawley rats (375-425?g) were subjected to 35% cecal ligation and puncture (CLP) (t?=?0?h). Twenty-two hours post-CLP and prior to resuscitation (t?=?22?h), animals were randomized to resuscitation with normal saline (NS, 10?cc/kg/h) or pooled rat fresh frozen plasma (FFP, 3.33?cc/kg/h). Resuscitation under general anesthesia proceeded for the next 6 h (t?=?22?h to t?=?28?h); lactate was checked every 2?h, and fluid volumes were titrated based on lactate clearance. Blood samples were obtained before (t?=?22?h) and after resuscitation (t?=?28?h), and at death or study conclusion. Lung specimens were obtained for calculation of wet-to-dry weight ratio. Fisher exact test was used to analyze the primary outcome of 48-h survival. ANOVA with repeated measures was used to analyze the effect of FFP versus NS resuscitation on blood gas, electrolytes, blood urea nitrogen (BUN), creatinine, interleukin (IL)-6, IL-10, catecholamines, and syndecan-1 (marker for endothelial injury). A two-tailed alpha level of <0.05 was used for all statistical tests. RESULTS:Thirty-three animals were studied: 14 FFP, 14 NS, and 5 sham. Post-CLP but preresuscitation (t?=?22?h) variables between FFP and NS animals were similar and significantly deranged compared with sham animals. FFP significantly increased 48-h survival compared to NS (n?=?8 [57%] vs n?=?2 [14%]), attenuated the post-resuscitation (t?=?28?h) levels of epinephrine (mean 2.2 vs 7.0?ng/mL), norepinephrine, (3.8 vs 8.9?ng/mL), IL-6 (3.8 vs 18.7?ng/mL), and syndecan-1 (21.8 vs 31.0?ng/mL) (all P?<?0.05), improved the post-resuscitation PO2 to FiO2 ratio (353 vs 151), and reduced the pulmonary wet-to-dry weight ratio (5.28 vs 5.94) (all P?<?0.05). CONCLUSION:Compared to crystalloid, plasma resuscitation increased 48-h survival in a rat sepsis model, improved pulmonary function and decreased pulmonary edema, and attenuated markers for inflammation, endothelial injury, and catecholamines.

Dataset Information

Impact of burn priming on immune and metabolic functions of whole Liver in a rat cecal ligation and puncture model.

Publications

Impact of burn priming on immune and metabolic functions of whole Liver in a rat cecal ligation and puncture model.

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