45 Unravelling the Unique Burn-induced Temporal Alterations in Adipose Tissue Metabolism

2020 ◽  
Vol 41 (Supplement_1) ◽  
pp. S30-S30
Author(s):  
Carly M Knuth ◽  
Chris Auger ◽  
Abdikarim Abdullahi ◽  
Marc G Jeschke
Keyword(s):  
Adipose Tissue ◽  
Murine Model ◽  
Burn Injury ◽  
Total Body Surface Area ◽  
Time Dependent ◽  
Metabolic Effects ◽  
Whole Body ◽  
Potential Contribution ◽  
Significant Difference ◽  
Tissue Browning

Abstract Introduction A severe burn elicits a systemic hypermetabolic response that substantially alters the function of multiple organs and contributes to increased morbidity and mortality. A consequence of hypermetabolism is the activation of UCP1-mediated browning of white adipose tissue (WAT), which may further facilitate the hypermetabolic response. In this study, we aimed to provide comprehensive characterization of the acute and long term pathophysiological responses to burns to determine the persistence of adipose tissue browning and its potential contribution to the hypermetabolic response. Methods Mice were subjected to either a 30% total body surface area (TBSA) scald burn or were denoted sham. Body weight and food intake were monitored throughout the duration of the study. Cohorts were sacrificed at 6hrs, 1, 3, 5, 7, 14, 30 and 60d post-burn and adipose tissue depots were harvested. Mitochondrial respiration, protein expression, and morphology in adipose tissues were assessed. Results Despite consuming considerably more food, the burn group lost significantly more weight throughout the duration of the study. We also detected increases in free fatty acids and interleukin-6, markers of whole-body lipolysis and inflammation, respectively. At the tissue level, eWAT mass significantly decreased over time, suggesting that this depot provides substrate to fuel the hypermetabolic response. This was further supported by a decrease in adipocyte area and an increase in lipolytic markers which remains significant up until 60d post-burn relative to sham. There were no significant difference in iWAT mass, however we detected significant increases in the protein content of UCP1, the master regulator of adipose tissue browning, as early as day 3 which persisted until day 60. This was corroborated by the presence of UCP1+ adipocytes. Conclusions Consistent with previous human studies, a burn injury elicits a dynamic response that cannot be simply characterized by a single timepoint. The alterations that occur in adipose tissue are depot-specific, time-dependent, and this notion likely extends to other metabolic tissues. Further, we demonstrate that in our 30% TBSA burn murine model, the effects of the hypermetabolic response persist for up to 60 days following initial injury. Applicability of Research to Practice Our data indicate the hypermetabolic response persists for up to 60 days, the equivalent of approximately 7 years in humans. This underscores the severity of adipose tissue browning and potentially provides an explanation as to how the hypermetabolic response persists even after the wound has healed. Moreover, providing a comprehensive map of the time-dependent changes in a murine model gives clinicians a better indication of the metabolic effects in a burn patient and will contribute to the development of effective, targeted treatments.

scholarly journals Effects of Physiological Hypercortisolemia on the Regulation of Lipolysis in Subcutaneous Adipose Tissue1

1998 ◽  
Vol 83 (2) ◽  
pp. 626-631 ◽  
Author(s):  
Jaswinder S. Samra ◽  
Mo L. Clark ◽  
Sandy M. Humphreys ◽  
Ian A. MacDonald ◽  
Peter A. Bannister ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Lipoprotein Lipase ◽  
Sodium Succinate ◽  
Hormone Sensitive Lipase ◽  
Whole Body ◽  
Constant Infusion ◽  
Nonesterified Fatty Acid ◽  
Significant Difference ◽  
Hormone Sensitive ◽  
Subcutaneous Adipose

Cortisol is known to increase whole body lipolysis, yet chronic hypercortisolemia results in increased fat mass. The main aim of the study was to explain these two apparently opposed observations by examining the acute effects of hypercortisolemia on lipolysis in subcutaneous adipose tissue and in the whole body. Six healthy subjects were studied on two occasions. On one occasion hydrocortisone sodium succinate was infused iv to induce hypercortisolemia (mean plasma cortisol concentrations, 1500 ± 100 vs. 335± 25 nmol/L; P < 0.001); on the other occasion (control study) no intervention was made. Lipolysis in the sc adipose tissue of the anterior abdominal wall was studied by measurement of arterio-venous differences, and lipolysis in the whole body was studied by constant infusion of[ 1,2,3-2H5]glycerol for measurement of the systemic glycerol appearance rate. Hypercortisolemia led to significantly increased arterialized plasma nonesterified fatty acid (NEFA; P < 0.01) and blood glycerol concentrations (P < 0.05), with an increase in systemic glycerol appearance (P < 0.05). However, in sc abdominal adipose tissue, hypercortisolemia decreased veno-arterialized differences for NEFA (P < 0.05) and reduced NEFA efflux (P < 0.05). This reduction was attributable to decreased intracellular lipolysis (P < 0.05), reflecting decreased hormone-sensitive lipase action in this adipose depot. Hypercortisolemia caused a reduction in arterialized plasma TAG concentrations (P < 0.05), but without a significant change in the local extraction of TAG (presumed to reflect the action of adipose tissue lipoprotein lipase). There was no significant difference in plasma insulin concentrations between the control and hypercortisolemia study. Site-specific regulation of the enzymes of intracellular lipolysis (hormone-sensitive lipase) and intravascular lipolysis (lipoprotein lipase) may explain the ability of acute cortisol treatment to increase systemic glycerol and NEFA appearance rates while chronically promoting net central fat deposition.

Metabolic Effects of Acute Hyperketonaemia in Man before and during An Hyperinsulinaemic Euglycaemic Clamp

1994 ◽  
Vol 86 (6) ◽  
pp. 677-687 ◽  
Author(s):  
J. Webber ◽  
E. Simpson ◽  
H. Parkin ◽  
I. A. MacDonald
Keyword(s):  
Adipose Tissue ◽  
Glucose Uptake ◽  
Glucose Oxidation ◽  
Respiratory Exchange Ratio ◽  
Saline Infusion ◽  
Metabolic Effects ◽  
Whole Body ◽  
Glucose Storage ◽  
Adipose Tissue Lipolysis ◽  
Subcutaneous Abdominal Adipose Tissue

1. The effects of acutely raising blood ketone body levels to those seen after 72 h of starvation were examined in 10 subjects after an overnight fast. Metabolic rate and respiratory exchange ratio were measured with indirect calorimetry before and during an insulin—glucose clamp. Arteriovenous differences were measured across forearm and subcutaneous abdominal adipose tissue. 2. In response to the clamp the respiratory exchange ratio rose from 0.82 to 0.83 during 3-hydroxybutyrate infusion and from 0.83 to 0.94 during control (saline) infusion (P < 0.001). 3. Forearm glucose uptake at the end of the clamp was 4.02 ± 0.95 (3-hydroxybutyrate infusion) and 7.09 ± 1.24 mmol min−1 100 ml−1 forearm (saline infusion). Whole body glucose uptake at the end of the clamp was 72.8 ± 7.9 (3-hydroxybutyrate infusion) and 51.0 ± 3.0 (saline infusion) mmol min−1 kg−1 body weight−1. 4. 3-Hydroxybutyrate infusion reduced the baseline abdominal venous—arterialized venous glycerol difference from 84 ± 28 to 25 ± 12 mmol/l and the non-esterified fatty acid difference from 0.60 ± 0.17 to 0.02 ± 0.09 mmol/l (P < 0.05 versus saline infusion). 5. Hyperketonaemia reduces adipose tissue lipolysis and decreases insulin-mediated forearm glucose uptake. Hyperketonaemia appears to prevent insulin-stimulated glucose oxidation, but does not reduce insulin-mediated glucose storage.

scholarly journals A Comparative Study between C-Reactive Protein and Procalcitonin in Iraqi Burn Patients

2017 ◽  
Vol 28 (1) ◽  
pp. 41
Author(s):  
Alia E. Al-Ubadi
Keyword(s):  
Burn Injury ◽  
Total Body Surface Area ◽  
Latex Agglutination ◽  
Burn Patients ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Survivor Group ◽  
Significant Difference ◽  
The Mean ◽  
Total Body

Association between Procalcitonin (PCT) and C-reactive protein (CRP) and burn injury was evaluated in 80 burned patients from Al-Kindy and Imam Ali hospitals in Baghdad-Iraq. Patients were divided into two groups, survivor group 56 (70%) and non-survivor group 24 (30%). PCT was estimated using (Human Procalcitonin ELISA kit) provided by RayBio/USA while CRP was performed using a latex agglutination kit from Chromatest (Spain). Our results declared that the mean of Total Body Surface Area (TBSA %) affected were 63.5% range (36%–95%) in non-survivor patients, while 26.5% range (10%–70%) in survivor patients. There is a significant difference between the two groups (P = 0.00), the higher mean percentage of TBSA has a significant association with mortality. Serum PCT and CRP were measured at the three times of sampling (within the first 48hr following admission, after 5thdays and after 10th days). The mean of PCT serum concentrations in non-survivor group (2638 ± 3013pg/ml) were higher than that of survivor group (588 ± 364pg/ml). Significantly high levels of CRP were found between the survivor and non-survivor groups especially in the 10th day of admission P=0.000, present study show that significant differences is found within the non-survivor group through the three times P= 0.01, while results were near to significant differences within survivor group through the three times (P= 0.05).

664 Risk Factors for the Development of Transaminitis in Pediatric Burn Patients Treated with Oxandrolone

2020 ◽  
Vol 41 (Supplement_1) ◽  
pp. S177-S177
Author(s):  
Kate Pape ◽  
Sarah Zavala ◽  
Rita Gayed ◽  
Melissa Reger ◽  
Kendrea Jones ◽  
...  
Keyword(s):  
Risk Factors ◽  
Length Of Stay ◽  
Pediatric Patients ◽  
Burn Injury ◽  
Total Body Surface Area ◽  
Future Research ◽  
Burn Patients ◽  
Thermal Burn ◽  
Increased Risk ◽  
Significant Difference

Abstract Introduction Oxandrolone is an anabolic steroid that is the standard of care for burn patients experiencing hypermetabolism. Previous studies have demonstrated the benefits of oxandrolone, including increased body mass and improved wound healing. One of the common side effects of oxandrolone is transaminitis, occurring in 5–15% of patients, but little is known about associated risk factors with the development of transaminitis. A recent multicenter study in adults found that younger age and those receiving concurrent intravenous vasopressors or amiodarone were more likely to develop transaminitis while on oxandrolone. The purpose of this study was to determine the incidence and identify risk factors for the development of transaminitis in pediatric burn patients receiving oxandrolone therapy. Methods This was a multicenter, retrospective risk factor analysis that included pediatric patients with thermal burn injury (total body surface area [TBSA] &gt; 10%) who received oxandrolone over a 5-year time period. The primary outcome of the study was the development of transaminitis while on oxandrolone therapy, which was defined as aspartate aminotransferase (AST) or alanine aminotransferase (ALT) &gt;100 mg/dL. Secondary outcomes included mortality, length of stay, and change from baseline ALT/AST. Results A total of 55 pediatric patients from 5 burn centers met inclusion criteria. Of those, 13 (23.6%) developed transaminitis, and the mean time to development of transaminitis was 17 days. Patients who developed transaminitis were older (12 vs 6.4 years, p = 0.01) and had a larger mean %TBSA (45.9 vs 34.1, p = 0.03). The odds of developing transaminitis increased by 23% for each 1 year increase in age (OR 1.23, CI 1.06–1.44). The use of other concurrent medications was not associated with an increased risk of developing transaminitis. Renal function and hepatic function was not associated with the development of transaminitis. There was no significant difference in length of stay and mortality. Conclusions Transaminitis occurred in 23.6% of our study population and was associated with patients who were older and had a larger mean %TBSA burn. Older pediatric patients with larger burns who are receiving oxandrolone should be closely monitored for the development of transaminitis. Applicability of Research to Practice Future research is needed to identify appropriate monitoring and management of transaminitis in oxandrolone-treated pediatric burn patients.

scholarly journals Minor role of mature adipocyte mineralocorticoid receptor in high-fat diet-induced obesity

2018 ◽  
Vol 239 (2) ◽  
pp. 229-240 ◽  
Author(s):  
A Feraco ◽  
A Armani ◽  
R Urbanet ◽  
A Nguyen Dinh Cat ◽  
V Marzolla ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Mouse Model ◽  
High Fat Diet ◽  
Mineralocorticoid Receptor ◽  
Metabolic Effects ◽  
Minor Role ◽  
High Fat ◽  
Mature Adipocyte ◽  
Diet Induced Obesity ◽  
Significant Difference

Obesity is a major risk factor that contributes to the development of cardiovascular disease and type 2 diabetes. Mineralocorticoid receptor (MR) expression is increased in the adipose tissue of obese patients and several studies provide evidence that MR pharmacological antagonism improves glucose metabolism in genetic and diet-induced mouse models of obesity. In order to investigate whether the lack of adipocyte MR is sufficient to explain these beneficial metabolic effects, we generated a mouse model with inducible adipocyte-specific deletion of Nr3c2 gene encoding MR (adipo-MRKO). We observed a significant, yet not complete, reduction of Nr3c2 transcript and MR protein expression in subcutaneous and visceral adipose depots of adipo-MRKO mice. Notably, only mature adipocyte fraction lacks MR, whereas the stromal vascular fraction maintains normal MR expression in our mouse model. Adipo-MRKO mice fed a 45% high-fat diet for 14 weeks did not show any significant difference in body weight and fat mass compared to control littermates. Glucose and insulin tolerance tests revealed that mature adipocyte MR deficiency did not improve insulin sensitivity in response to a metabolic homeostatic challenge. Accordingly, no significant changes were observed in gene expression profile of adipogenic and inflammatory markers in adipose tissue of adipo-MRKO mice. Moreover, pharmacological MR antagonism in mature primary murine adipocytes, which differentiated ex vivo from WT mice, did not display any effect on adipokine expression. Taken together, these data demonstrate that the depletion of MR in mature adipocytes displays a minor role in diet-induced obesity and metabolic dysfunctions.

scholarly journals Thermoneutrality Reduces the Beneficial Metabolic Effects of Eicosapentaenoic Acid on White Adipose Tissue in Diet-Induced Obese Mice

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1254-1254
Author(s):  
Bimba Goonapienuwala ◽  
Mandana Pahlavani ◽  
Latha Ramalingam ◽  
Kembra Albracht-Schulte ◽  
William Festuccia ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Glucose Tolerance ◽  
Eicosapentaenoic Acid ◽  
Uncoupling Protein ◽  
Serum Triglyceride ◽  
Metabolic Effects ◽  
Omega 3 ◽  
Adipocyte Size ◽  
Mitochondrial Energy Metabolism ◽  
Significant Difference

Abstract Objectives At ambient temperature (23°C), eicosapentaenoic acid (EPA), an omega-3 polyunsaturated fatty acid reduces visceral adipose tissue (VAT) inflammation, adipocyte size and improves overall metabolic profile in diet-induced obese (DIO) mice, potentially through upregulation of uncoupling protein 1 (UCP-1). The goal of this study is to determine whether effects of EPA are maintained at thermoneutrality, and/or mediated by UCP-1, and if so through which cellular mechanisms. Methods Wild type (WT) and UCP-1 knockout (KO) B6 male mice were housed at thermoneutral temperature (28–30°C) and fed high fat (HF, 45% kcal fat) supplemented with or without EPA (36 g/kg diet). Serum, VAT (epididymal fat) and cecal microbiome specimens were analyzed. Results EPA reduced adiposity and improved glucose tolerance in EPA-fed KO mice (P &lt; 0.05), but not in EPA-fed WT mice. EPA supplementation lowered VAT mass in both genotypes (P &lt; 0.05); however, there were no diet or genotype-related differences in adipocyte size or serum triglyceride levels. Both genotypes fed EPA had lower serum resistin levels compared to respective HF (P &lt; 0.01). EPA showed trends towards increased serum adiponectin levels compared to HF fed mice in both genotypes, with KO-EPA group having the highest concentration. There was no significant difference in the expression of IL-6 in VAT among the groups, while MCP-1 mRNA was expressed more in KO groups compared to WT groups (P &lt; 0.01). Diet had no effect on expression of anti-inflammatory markers in both WT and KO mice. There were no genotype or diet effects on expression of genes involved in lipid metabolism and mitochondrial energy metabolism. Cecal microbiome showed no differences in the species diversity (Shannon index) between genotypes or diet types. However, only in the KO group, the Bacteroidetes/Firmicutes ratio was increased by EPA. Conclusions Compared to previous work at ambient temperatures, VAT does not mediate protective effects of EPA in DIO mice at thermoneutral temperature. Moreover, EPA effects are independent of UCP-1 as it produced beneficial effects on glucose tolerance and adiposity in KO mice, which may be in part mediated by changes in microbiome. Further mechanistic studies are ongoing to understand the mechanisms mediating EPA and UCP-1 effects in VAT. Funding Sources Funded by NIH (NCCIH and NIA).

Pulmonary changes in a mouse model of combined burn and smoke inhalation-induced injury

2008 ◽  
Vol 105 (2) ◽  
pp. 678-684 ◽  
Author(s):  
Akio Mizutani ◽  
Perenlei Enkhbaatar ◽  
Aimalohi Esechie ◽  
Lillian D. Traber ◽  
Robert A. Cox ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Murine Model ◽  
Burn Injury ◽  
Total Body Surface Area ◽  
Inhalation Injury ◽  
Smoke Inhalation ◽  
Inos Mrna ◽  
Myeloperoxidase Activity ◽  
Smoke Inhalation Injury ◽  
Injury Group

The morbidity and mortality of burn victims increase when burn injury is combined with smoke inhalation. The goal of the present study was to develop a murine model of burn and smoke inhalation injury to more precisely reveal the mechanistic aspects of these pathological changes. The burn injury mouse group received a 40% total body surface area third-degree burn alone, the smoke inhalation injury mouse group received two 30-s exposures of cotton smoke alone, and the combined burn and smoke inhalation injury mouse group received both the burn and the smoke inhalation injury. Animal survival was monitored for 120 h. Survival rates in the burn injury group, the smoke inhalation injury group, and the combined injury group were 70%, 60%, and 30%, respectively. Mice that received combined burn and smoke injury developed greater lung damage as evidenced by histological changes (septal thickening and interstitial edema) and higher lung water content. These mice also displayed more severely impaired pulmonary gas exchange [arterial Po2(PaO2)/inspired O2fraction (FiO2) < 200]. Lung myeloperoxidase activity was significantly higher in burn and smoke-injured animals compared with the other three experimental groups. Plasma NO2−/NO3−, lung inducible nitric oxide synthase (iNOS) activity, and iNOS mRNA increased with injury; however, the burn and smoke injury group exhibited a higher response. Severity of burn and smoke inhalation injury was associated with more pronounced production of nitric oxide and accumulation of activated leukocytes in lung tissue. The murine model of burn and smoke inhalation injury allows us to better understand pathophysiological mechanisms underlying cardiopulmonary morbidity secondary to burn and smoke inhalation injury.

scholarly journals The epidemiology of burn injury among children during COVID-19 19 pandemic and WFH policy in Malang, East Java, Indonesia

2021 ◽  
Vol 10 (4) ◽  
pp. 744
Author(s):  
Herman Yosef Limpat Wihastyoko ◽  
Arviansyah Arviansyah ◽  
Erdo Puncak Sidarta
Keyword(s):  
Comparative Analysis ◽  
Body Surface ◽  
Clinical Characteristics ◽  
Burn Injury ◽  
Total Body Surface Area ◽  
Burn Injuries ◽  
Work From Home ◽  
Injury Group ◽  
Significant Difference ◽  
Total Body

Work from home (WFH) mandate is one of the major changes known during this pandemic, aimed as a preventive way to mitigate the spread of the COVID-19 virus. This study aimed to observe the characteristics of pediatric burn injury during COVID-19 pandemic and WFH mandate's impact on pediatric burn injury admission at some Hospital burn centers in Malang. Every patient’s age, gender, clinical characteristics, parent's background, and other variables such as the possession of siblings, response time using our burn registry form, and comparative analysis of the incident in WFH housewife mother were assessed. The majority were in the group age of under five years old group age (70%) with a mean of 5.5 years. The most frequent part of the burn injured is extremity 36.7%, and hot liquid dominates as the cause of the injury 73.3% with the total body surface area of burn injury group &gt;10% is the most common 56.7%. The burn injury incident happened more frequently in mothers with children less than two in both groups. This study showed that the increase in increasement of the pediatric burn injury during COVID-19 pandemic between housewife mother and WFH mother has no significant difference also showed that parent especially mother unable to supervise the children during WFH. Strategies to mitigate pediatric burn injuries during WFH should be thoughtfully implemented.

Thermal injury impairs cardiac protein synthesis and is associated with alterations in translation initiation

2004 ◽  
Vol 286 (4) ◽  
pp. R740-R750 ◽  
Author(s):  
Charles H. Lang ◽  
Robert A. Frost ◽  
Thomas C. Vary
Keyword(s):  
Protein Synthesis ◽  
Translation Initiation ◽  
Thermal Injury ◽  
Burn Injury ◽  
Total Body Surface Area ◽  
Mrna Translation ◽  
Translation Efficiency ◽  
High Mobility Group Protein ◽  
Translational Repressor ◽  
Significant Difference

The purpose of the present study was to determine whether burn injury decreases myocardial protein synthesis and potential contributing mechanisms for this impairment. To address this aim, thermal injury was produced by a 40% total body surface area full-thickness scald burn in anesthetized rats, and the animals were studied 24 h later. Burn decreased the in vivo-determined rate of myocardial protein synthesis and translation efficiency by 25% but did not alter the protein synthetic rate in skeletal muscle. To identify potential mechanisms responsible for regulating mRNA translation in cardiac muscle, we examined several eukaryotic initiation factors (eIFs) and elongation factors (eEFs). Burn failed to alter eIF2B activity or the total amount or phosphorylation status of either eIF2α or eIF2Bϵ in heart. In contrast, hearts from burned rats demonstrated 1) an increased binding of the translational repressor 4E-BP1 with eIF4E, 2) a decreased amount of eIF4E associated with eIF4G, and 3) a decreased amount of the hyperphosphorylated γ-form of 4E-BP1. These changes in eIF4E availability were not seen in gastrocnemius muscle where burn injury did not decrease protein synthesis. Furthermore, constitutive phosphorylation of mTOR, S6K1, the ribosomal protein S6, and eIF4G were also decreased in hearts from burned rats. Burn did not appear to adversely affect elongation because there was no significant difference in the myocardial content of eEF1α or eEF2 or the phosphorylation state of eEF2. The above-mentioned burn-induced changes in mRNA translation were associated with an impairment of in vitro myocardial performance. Finally, 24 h postburn, the cardiac mRNA content of IL-1β, IL-6, and high-mobility group protein B1 (but not TNF-α) was increased. In summary, these data suggest that thermal injury specifically decreases cardiac protein synthesis in part by decreasing mRNA translation efficiency resulting from an impairment in translation initiation associated with alterations in eIF4E availability and S6K1 activity.

132 A Novel Murine Model of Burn-Induced Platelet Dysfunction

2021 ◽  
Vol 42 (Supplement_1) ◽  
pp. S88-S89
Author(s):  
Breanne H Gibson ◽  
Matthew T Duvernay ◽  
Stephen Gondek ◽  
Jonathan G Schoenecker
Keyword(s):  
Clinical Significance ◽  
Platelet Function ◽  
Murine Model ◽  
Molecular Mechanisms ◽  
Burn Injury ◽  
Platelet Dysfunction ◽  
Significant Difference ◽  
Platelet Signaling ◽  
Cellular Markers ◽  
And Function

Abstract Introduction Platelet dysfunction has been demonstrated as a part of burn induced coagulopathy (BIC), however, the etiology and clinical significance are unknown. Determining the etiology and clinical significance of BIC platelet dysfunction is difficult in humans due to heterogeneity of injuries and treatment. The goal of this study was to develop a murine model of BIC burn-induced platelet dysfunction to allow for high-throughput investigation of the mechanisms and the possible effects platelet dysfunction has on burn outcomes. Methods Using an established murine model of burn injury, we investigated plasma and cellular markers of BIC. Under adequate anesthesia and analgesia six-week-old C57BL6/J mice were administered a ~30% TBSA dorsal burn by scalding. Sham animals received identical preparation and resuscitation without the burn injury. Blood was collected at 6-, 24-, and 48-hours post-burn for measurement of platelet function, and plasma was isolated for protein measurements of coagulopathy (N=5 per group per time point). Results Like findings in humans, mice exhibited systemic markers of BIC (excess coagulation, fibrinolysis, and inflammation) within the first 6–24 hours post-burn. Platelets in whole blood were treated with platelet agonists ADP and PAR4-activating peptide (PAR4AP), and markers of platelet signaling and function (P-selectin expression and GpIIb/IIIa activation) were measured by flow cytometry. At 6 hours post-procedure, platelets from burn mice exhibited a slight, insignificant increase in markers of activation and response to stimulation compared with platelets from sham mice. At 24 hours post-burn, burn mice exhibited a significant decrease in platelet count (P&lt; 0.02) and platelet function indicated by reduced GpIIb/IIIa activation (P&lt; 0.01) and P-selectin expression (P&lt; 0.05)in response to ADP and PAR4-AP compared with sham mice. Platelet function began to return at 48 hours post-burn with no significant difference between groups. Conclusions Platelet loss and dysfunction occur after burn injury, but the consequence of these effects is not well understood. The findings in this study are consistent across multiple experiments and resembled platelet dysfunction observed in different human traumatic injuries, validating the murine model as an inexpensive and efficient model of human injury in which to study platelet defects and the molecular mechanisms driving them.

Sign in / Sign up

Export Citation Format

Share Document