Increased oxidative phosphorylation in lymphocytes does not atone for decreased cell numbers after burn injury

The acute systemic inflammatory response syndrome (SIRS) and multiorgan dysfunction (MOD) that occur in large burn injuries may be attributed, in part, to immunosuppressive responses such as decreased lymphocytes. However, the mitochondrial bioenergetics of lymphocytes after severe burn injury are poorly understood. The purpose of this study was to examine mitochondrial function of lymphocytes following severe burns in a swine model. Anesthetized Yorkshire swine ( n = 17) sustained 40% total body surface area full-thickness contact burns. Blood was collected at pre-injury (Baseline; BL) and at 24 and 48 h after injury for complete blood cell analysis, flow cytometry, cytokine analysis, and ficoll separation of intact lymphocytes for high-resolution mitochondrial respirometry analysis. While neutrophil numbers increased, a concomitant decrease was found in lymphocytes ( P < 0.001) after burn injury, which was not specific to CD4+ or CD8+ lymphocytes. No changes in immune cell population were observed from 24 h to 48 h post-injury. IL 12-23 decreased while a transient increase in IL 4 was found from BL to 24h ( P < 0.05). CRP progressively increased from BL to 24h ( P < 0.05) and 48h ( P < 0.001) post-injury. Routine and maximal mitochondrial respiration progressively increased from BL to 24h ( P < 0.05) and 48 h post-injury ( P < 0.001). No changes were found in leak respiration or residual oxygen consumption. When considering the reduction in lymphocyte number, the total peripheral lymphocyte bioenergetics per volume of blood significantly decreased from BL to 24h and 48h (P < 0.05). For the first time, we were able to measure mitochondrial activity in intact lymphocyte mitochondria through high-resolution respirometry in a severely burned swine model. Our data showed that the non-specific reduction in peripheral T cells after injury was larger than the increased mitochondrial activity in those cells, which may be a compensatory mechanism for the total reduction in lymphocytes. Additional studies in the metabolic activation of T cell subpopulations may provide diagnostic or therapeutic targets after severe burn injury.

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Severe Burn Injury in a Swine Model for Clinical Dressing Assessment

Journal of Visualized Experiments ◽

10.3791/57942 ◽

2018 ◽

Cited By ~ 1

Author(s):

Gang-Yi Fan ◽

Juin-Hong Cherng ◽

Shu-Jen Chang ◽

Raju Poongodi ◽

Chih-Hsin Wang ◽

...

Keyword(s):

Burn Injury ◽

Swine Model ◽

Severe Burn ◽

Severe Burn Injury

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Sodium variability is associated with increased mortality in severe burn injury

Burns & Trauma ◽

10.1186/s41038-017-0098-4 ◽

2017 ◽

Vol 5 ◽

Cited By ~ 6

Author(s):

Soman Sen ◽

Nam Tran ◽

Brian Chan ◽

Tina L. Palmieri ◽

David G. Greenhalgh ◽

...

Keyword(s):

Serum Sodium ◽

Burn Injury ◽

Total Body Surface Area ◽

Multivariate Logistic Regression Analysis ◽

Median Number ◽

High Plasma ◽

Plasma Sodium ◽

Burn Patients ◽

Severe Burn ◽

Severe Burn Injury

Abstract Background Dysnatremias are associated with increased mortality in critically ill patients. Hypernatremia in burn patients is also associated with poor survival. Based on these findings, we hypothesized that high plasma sodium variability is a marker for increased mortality in severely burn-injured patients. Methods We performed a retrospective review of adult burn patients with a burn injury of 15% total body surface area (TBSA) or greater from 2010 to 2014. All patients included in the study had at least three serum sodium levels checked during admission. We used multivariate logistic regression analysis to determine if hypernatremia, hyponatremia, or sodium variability independently increased the odds ratio (OR) for death. Results Two hundred twelve patients met entry criteria. Mean age and %TBSA for the study was 45 ± 18 years and 32 ± 19%. Twenty-nine patients died for a mortality rate of 14%. Serum sodium was measured 10,310 times overall. The median number of serum sodium measurements per patient was 22. Non-survivors were older (59 ± 19 vs. 42 ± 16 years) and suffered from a more severe burn injury (50 ± 25% vs. 29 ± 16%TBSA). While mean sodium was significantly higher for non-survivors (138 ± 3 milliequivalents/liter (meq/l)) than for survivors (135 ± 2 meq/l), mean sodium levels remained within the laboratory reference range (135 to 145 meq/l) for both groups. Non-survivors had a significantly higher median number of hypernatremic (> 145 meq/l) measurements (2 vs. 0). Coefficient of variation (CV) was significantly higher in non-survivors (2.85 ± 1.1) than survivors (2.0 ± 0.7). Adjusting for TBSA, age, ventilator days, and intensive care unit (ICU) stay, a higher CV of sodium measurements was associated with mortality (OR 5.8 (95% confidence interval (CI) 1.5 to 22)). Additionally, large variation in sodium ranges in the first 10 days of admission may be associated with increased mortality (OR 1.35 (95% CI 1.06 to1.7)). Conclusions Increased variability in plasma sodium may be associated with death in severely burned patients.

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