Severe Thermal Trauma Research Articles

The Influence of Singlet Oxygen Inhalations on Rats with Experimental Burn Trauma

This article aims to study the dynamics of the crystallogenic properties of rat blood serum during a course of singlet oxygen inhalation in the post-burn period. The experiment was performed on 30 mature Wistar rats randomly divided into three groups of equal numbers. The first group (n=10) was intact, no manipulations were performed on the animals included in it, but only a single blood irradiation from the sublingual vein was performed. The animals of the second (control) and third (main) groups under combined anesthesia were subjected to thermal trauma according to our methodology, standard local treatment was carried out. Starting from the day following the injury, the rats of the main group were inhaled daily for 10 days of the airflow coming from the singlet oxygen generator. Blood samples from rats of all groups were collected and tested for crystallogenic properties and crystallogenesis-inducing activity. It was found that the inhalation of singlet oxygen in animals with severe thermal trauma contributes to the partial normalization of the crystallogenic activity of blood serum, which positively characterizes its rehabilitation potential. This trend must take place when assessing both the intrinsic crystallogenic and initiating properties of biological fluid, which is manifested both in the dynamics of morphological and morphometric indicators and the optical characteristics of serum facies.

Morphofunctional Properties of Spindle-Shaped Platelets

Morphofunctional properties of spindle-shaped platelets under normal and pathological conditions were studied by the method based on vital staining. In donor blood and plasma isolated by centrifugation at 300g, no spindle-shaped platelets were detected; after centrifugation at 3000g, spindle-shaped platelets were detected in a small amount in 20% samples. During plasma storage at 20-22°C, spindle-shaped platelets appeared after 1-2 days, after 3 days their number increased to 30% and higher. Spindle-shaped platelets contained a small number of granules and did not exhibit active adhesion, while the structure of their membranes was normal after 1-2 days of storage and abnormalities appeared during subsequent storage. Spindle-shaped platelets were found in the blood of patients with acute exogenous poisoning and severe thermal trauma. Spindle-shaped platelets can be used as an additional criterion for assessing the quality of the platelet population.

Successful treatment of severely burned pediatric patient with comorbid disease burden

Combustion pathology remains one of the most topical and social important problems of practical public health. A special category of burned patients are children with numerous comorbidities. Purpose - to present the clinical case of successful management of severe burn victim – the child with numerous birth defects and comorbidities. Materials and methods. A 7-year-old male patient V. The diagnosis «Third-degree flame burn, 45% of the total body surface area in the regions of upper extremities, buttocks, lower extremities. Mummification of the feet and legs - to the middle third. Inhalation injury. Burn disease. Burn shock, grade IV. Cerebral palsy. Unbalanced chromosome pathology. Statokinetic development delay. Psychomotor development retardation. Hyperhomocysteinemia. Muscle hypotension syndrome. Acute gastritis. Congenital heart disease. Arachnoid cyst. Partial optic nerve atrophy. Concomitant convergent strabismus. Right-sided abdominal cryptorchidism. Aphthous dermatitis. Polyvalent food allergy». The patient underwent early necrectomy-amputation, three necrectomies followed by wound closure with xenoderm grafts, and four skin autografting procedures. Results. Extremely severe thermal trauma in patients with serious congenital pathology was previously thought by experts to be the injury incompatible with life. In the clinical case presented, the patient’s life was saved due to early surgical treatment, which included guillotine amputation-necrectomy of lower extremities aimed at radical debridement to prevent the development of severe burn disease, along with appropriate infusion and pharmacological therapy. Subsequent surgical procedures stabilized the patient’s condition, decreased the severity of injury, arrested the progression of burn disease, thus leading to his recovery. By the time of discharge from the hospital (on day 91 post injury), the wounds had completely healed, laboratory parameters were within normal limits. Conclusions. The prognoses like “the injury is not compatible with life, and treatment is symptomatic" should not be pronounced by clinicians in general and by burn experts in particular. To save the patient’s life by all possible means should be the primary goal for all medical professionals. The research was carried out in accordance with the principles of the Helsinki Declaration. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors. Keywords: burns, children, congenital malformations, concomitant pathology, treatment.

До питання щодо способів діагностики і прогнозування розвитку ускладнень у постраждалих з опіками (огляд літератури)

The aim. The article is devoted to the methods used in combustiology practice to assess the condition of patients and predict general and local complications. Results. With severe thermal trauma, there is a risk of developing life-threatening conditions in the victims, in particular, sepsis and multiple organ failure. Informative for assessing the course of burn disease is a modified scale of physiological disorders, which takes into account the syndrome of systemic inflammatory response, endogenous intoxication during periods of toxemia and septicotoxemia, and concomitant pathology. The development of intoxication in severe burn injuries requires determining the degree of severity of the process and its assessment in dynamics. The toxicity of blood plasma is studied by the resistance of red blood cell membranes in the acid hemolysis reaction, indicators of the red blood cell intoxication index, and the content of universal markers of intoxication, in particular, medium-weight molecules. Methods for biosensor indication of cytotoxic factors have also been developed. Assessment of the severity of the condition of victims with burns and monitoring the effectiveness of therapy is carried out taking into account the level of procalcitonin and presepsin. To determine the effect of the wound process on the formation of early sepsis in patients with burns in the capillary zone of thermal damage, the content of homocysteine, endothelin and nitric oxide is studied. To assess the severity of the condition of burn patients and predict the development of complications, the values of integral hematological indices are informative. Reliable data on the depth of a burn wound are obtained using thermotopometry and pH measurement of burn wounds, the method of magnetic resonance imaging. In order to assess violations and dynamics of blood supply restoration in the area of thermal damage, the method of laser Doppler flowmetry and optical tissue oximetry is used. Determination of interstitial pressure in burns of the extremities and intra-abdominal pressure in common burns is a way to predict the development of compartment syndrome. To monitor the patient's glycemic status, it is proposed to determine the level of glycosylated hemoglobin. Microbiological research data is used to predict the risk of developing general complications of burn disease, as well as – together with cytological data and methods for determining the maturity of granulation tissue – to assess the readiness of granulating wounds for autodermoplasty. Conclusion. The development of new effective ways to predict and prevent the development of complications in burns is promising

Role, Management, and Outcome of Free Flap Reconstruction for Acute Full-Thickness Burns in Hands

Severe thermal trauma to the hand can result in major impairment and reduced function due to defective healing or even extremity loss. Full-thickness injuries frequently incur exposure of tendons or bone and require an early and stable coverage with soft tissue transplants to allow for rapid induction of exercise and to preserve structures and hand function. Free tissue transfer to the hand after thermal trauma is a rare indication, and safety, management, and outcome of free flap surgery for severe acute burn injuries to the hand remains underreported. Patients with primary reconstructions of full-thickness burn injuries to the hand undergoing microsurgical free tissue transfer surgery were retrospectively assessed in a period from 2013 to 2016. Salvage strategy of the extremity, postoperative complications, length of hospital stay, and primary reconstructive result were quantified and analyzed. Functional outcome measures (range of motion and grip strength) were assessed during clinical follow-up examinations. During the investigated period, 13 patients were identified undergoing reconstruction of 14 hands via free flap transplantation after severe burn injury in the acute phase. Nine anteriolateral thigh flaps (64%), 3 latissimus dorsi flaps (18%), 1 serratus anterior flap, and 1 tensor fasciae lata flap (7%) were performed. In all cases, salvage of the affected extremity was achieved, although 1 flap (7%) was lost during the early postoperative period requiring secondary reconstruction via pedicled groin flap. Further complications were venous thrombosis (n = 2; 14%) and hematoma (n = 2; 14%). Mean length of hospital stay was 51 days. Functional outcome during follow-up examination after an average of 9.3 months was inhomogeneous depending on the pattern of injury and ranged from complete recovery to nearly entire loss of hand function. Free flap transfer can be a mandatory and valuable tool to cover full-thickness burn injuries of the hand early in the clinical course of thermal trauma and may provide extremity salvage by favorable means of reconstruction to achieve acceptable functional outcomes, in the most severe cases. Although microsurgical failure rates in burn patients are slightly higher than in free flap transfer to the upper extremity in general, it can be performed with reasonable risk-to-benefit ratio.

HISTOLOGICAL AND MORPHOMETRIC CHANGES OF THE RAT TESTES AFTER EXPERIMENTAL THERMAL INJURY AND APPLICATION OF XENODERMAL SUBSTRATE

The aim of this work was to establish the histological and morphometric changes of the structural components of the rat testes after experimental thermal trauma and under condition of correction. Object and methods. The study was performed on 48 sexually mature outbred white male rats following the rules of bioethics. The experimental animals were divided into three groups: intact; with severe thermal trauma; with burn injury and application of xenodermal substrate after early necrectomy of the damaged tissues. Results and discussion. Already on the 7th day after application of xenodermal substrate the processes of reparative regeneration of hemocapillaries is activated, the degree of vascular disorders and damages of the structural components of the testes are decreased, and regenerative processes are activated. The percentage of significantly altered seminiferous tubules is 1.90-fold lower than in animals without correction. In the later stages of the experiment, the usage of the xenodermal substrate contributes to an active flow of regenerative processes and a relative normalization of all the structural components of the testes. Morphometric indicators of mean values of diameter and area of convoluted tubes on the 21th day were significantly (p<0.001) higher by 1.39 times and 2.00 times relative to the indicators in the group of animals without correction. Areas with unchanged histostructure are dominated in the testes at this term. The percentage of significantly altered tubules was 10.58 times lower than the corresponding value in animals with burn injury without correction. Conclusions. Thus, the application of a xenodermal substrate on a wound formed after necrectomy of thermally damaged areas was found to contribute to a significant reduction of vascular disorders and destructive changes of spermatogenic cells. Better state of intracellular components and activation of regeneration contribute to a relative normalization of the testicular structure and morphometric indices in the later terms of the experiment.

Peculiarities of structural reorganization of the thyroid gland vessels in dynamics after experimental thermal trauma

Thermal trauma and burn disease, which develops from deep, large lesions, are accompanied by significant morphological and functional changes not only in the skin, but also in organs of all systems of the body, including thyroid gland. The purpose of the study was to establish a microscopic reorganization of the animal thyroid gland in dynamics after an experimental thermal trauma. Burns of the third degree were applied under ketamine anesthesia with copper plates heated in boiled water to a temperature of 97–100 °С. The affected area corresponded 18–20% of the surface of the rat’s body. Experimental study of structural changes in the vascular bed of the thyroid gland after severe thermal trauma was carried out on laboratory white male rats weighing 160–180 g. Euthanasia of rats was performed after ketamine anesthesia, by decapitation. Structural changes in the thyroid gland were studied after 1, 7, 14 and 21 days from the beginning of the experiment. Histologic sections of 5–6 µm thickness were stained with hematoxylin-eosin. For the study of the connective tissue condition and its main substance, silver impregnation was performed by using the Gordon-Sweet's method (to detect reticular and immature collagen fibers), staining with 3-colored MSB — selective coloring method for intravascular coagulation syndrome. It has been established that in the early stages after the thermal trauma (1–7 days of the experiment, the stage of shock and early toxemia) there are adaptive-compensatory changes and initial signs of destruction of the vascular bed structural components of the organ. In late terms (14–21 days of the experiment, the stages of late toxemia and septicotoxemia) significant destructive-degenerative changes of the thyroid gland arteries, veins and blood vessels of the hemocirculatory bed were detected. Therefore, a severe burn injury causes deep histological modification of the thyroid gland vessels, the degree of intensity of which depends on the time interval of the experiment, which adversely affects on the functioning of the organ and transvascular metabolic processes. In further researches it is planned to study the course of morphological changes of thyroid gland vessels during thermal trauma with combined application of corrective methods.

The Results of Gastric pH-metry in Patients with Extensive Burns

Aim of studyTo study of the role of hydrochloric acid in the genesis of stress-induced gastric ulceration in patients with extensive burns.Material and methodsThe results of gastroscopy and endoscopic pH-metry of 30 young patients with extensive burns (19 male patients and 11 female patients). The acidity of the gastric contents was measured on day 1,7 and 14 after the trauma.ResultsIt was found that the early period of burn disease was followed by the pH growth in the acid-producing area of the stomach to 3.8–4.2 (p=0.002–0.020). This indicated that extensive burns provoked a significant decrease of hydrochloric acid production by parietal cells of the stomach. The restoration of the acid production occurred only 14 days after thermal injury and was not followed by the development of a hyperacid state. The frequency of erosive-ulcerative lesions detection in the gastric mucosa by the end of the first day after receiving burns was 83%, 87% on day 7, and 96% on day 14. In total, stress-induced lesions of the gastrointestinal mucosa were diagnosed in 26 of 30 patients with a shock-induced thermal injury. Consequently, in patients with burn shock the protective factors of the gastric mucosa were depressed so that a minimum amount of hydrochloric acid was sufficient to damage it.ConclusionInhibition of acidogenic function is typical for patients with burn disease. Hydrochloric acid does not play a leading role in the genesis of stressinduced ulceration in patients with severe thermal trauma.

Functional Activity of Neutrophils in Burn Sepsis

A complex effect of thermal trauma on the immune system triggers the tendency to develop and generalize infection in patients with severe thermal trauma. The phagocytic system, which is represented, first of all, by neutrophilic granulocytes, is significantly altered. Objective: to determine the dynamics of changes in the functional activity of neutrophils in patients with thermal trauma, as well as its prognostic significance in the development of purulent-septic complications of a burn disease. Materials and methods. The functional activity of neutrophils was assessed by spontaneous and induced chemiluminescence responses of whole blood sequentially stimulated with phorbol-12-myristate"13-acetate(PMA) and N-formyl-methionyl-leucyl-phenylalanine (fMLP). 34 patients with a burn disease of different severity were dynamically examined during observation. Results. The newly developed technique was applied to study the responses of whole blood of patients with burn disease to stimuli; data on the functional activity of neutrophils depending on various severities of the disease and response dynamics were obtained. Analysis of chemiluminescent curves of the development of respiratory explosion of neutrophils helped to reveal parameters of the immune system state, namely: a one— or two-phase response to a stimulus, a «rapid phase» neutrophil specific activity, and a «slow phase» neutrophil specific activity. Conclusion. The results revealed trends in alterations of functional activity of neutrophils in burn disease. Diagnostic and prognostic indices of the functional activity of neutrophils for assessing the severity of the disease and the prognosis of the septic process were suggested.

Morphofunctional Modifications of Neurocytes of the Rat Hippocampal CA3 Area after Experimental Thermal Trauma

In experiments on mature male Wistar rats, the dynamics of morphological modifications of neurocytes of the hippocampal CA3 area after a severe thermal trauma were examined. The pattern and degree of morphofunctional changes in the nerve cells depended significantly on the time interval after thermal trauma; their intensity correlated with the stages of burn disease. At stages of acute shock and early toxemia (days 1 to 7), mostly effects that could be interpreted as adaptive/compensatory reactions were observed, although initial signs of destructive changes were also obvious. At stages of late toxemia and septicotoxemia (days 14 to 21), deep irreversible destructive modifications in a considerable part of neurocytes of the hippocampal CA3 area became appreciable. The proportions of neurocytes belonging to different morphological types and values of the nucleo-cytoplasmic ratio (NCR) in such cells changed significantly. After an experimental burn, the total density of neurocytes gradually decreased, while portions of sharply hypo- and hyperchromic cells, in which NCRs underwent maximum modifications, increased. Electron microscopy of CA3 nerve cell demonstrated the development of destructive changes in the nuclei and cytoplasmic structures (degranulation of the endoplasmic reticulum, decrease in the number of ribosomes and polysomes, hypertrophy of the mitochondria with clarification of their matrix and destruction of mitochondrial cristae, and increase in the number of lysosomes). Therefore, severe thermal trauma induces significant morphofunctional modifications of neurocytes in the hippocampal CA3 area.

Expression Signatures of LncRNAs in Skeletal Muscles at the Early Flow Phase in Burned Rats Revealed by Microarray

Severe thermal trauma covering more than 30% of the total body surface area (TBSA) triggers a sustained pathophysiological response, which includes, but is not limited to, hypermetabolism, chronic inflammation, and severe skeletal muscle wasting. Long non-coding RNAs (lncRNAs) are an important class of pervasive genes involved in a variety of biological functions. However, the functions of lncRNAs in the regulation of responses of skeletal muscle wasting after severe burn have remained untested. Presently examined were the expression profiles of lncRNAs and messenger RNAs (mRNAs) in skeletal muscle tissues of 3 pairs of burned rats at the early flow phase, compared with sham rats, using microarray. Each potential lncRNA-mRNA pair identified is a strong candidate in the definitive confirmation of the presence of specific lncRNA-mRNA interactions, thus providing a detailed picture of the pathogenesis of skeletal muscle wasting in burned rats. LncRNA expression levels were compared among 3 injured tissues and matched normal tissues from microarray data. An average of 117 significantly differentially expressed lncRNAs (1.5-fold) were identified. Only 202 mRNAs were significantly upregulated or downregulated, an average of 92 mRNAs were upregulated in injured, compared to matched normal, tissues, while an average of 110 mRNAs) were downregulated. Presently identified were lncRNAs differentially expressed in skeletal muscles of burned rats, compared to normal tissues. Regulatory pathways may be involved in the pathogenesis of skeletal muscle wasting. Each lncRNA-mRNA pair identified is a strong candidate for a future study to definitively confirm the presence of specific lncRNA-mRNA interactions, thus providing a more detailed picture of the pathogenesis of skeletal muscle wasting in burned rats.

Effect of early and late outpatient exercise training on muscle mass and protein kinetics in severely burned children (702.5)

Severe thermal trauma is associated with profound muscle wasting and long‐term functional impairments in burn survivors. Late exercise training performed 6 to 9 months post‐injury increases leg lean mass (LM) in burned children. The impact of early outpatient exercise, initiated immediately following hospital discharge, on muscle mass has yet to be examined. Therefore, we examined the effects of early and late outpatient rehabilitative exercise training (RET) on muscle mass and protein kinetics in severely burned children. Eighty‐six children with 蠅40% total body surface area burn were randomized to 12‐weeks standard of care rehabilitation (SoC) or RET at discharge (DC) and 6 months (6M) post‐burn. DEXA was used to determine changes in LM. In a subset of patients (N=30), stable isotope infusion studies were conducted to determine muscle protein synthesis (MPS). RET increased LM compared to SoC at each time‐point (DC: 4.7% vs 17.0%; 6M: 3.0% vs 13.0%). No differences in LM were found between RET interventions. MPS decreased from DC to 6M (6.3 ± 1.4% and 3.4 ± 0.6%, respectively); however no differences were observed between SoC and RET. No changes in MPS were observed from 6 to 9 months. In addition, no differences in blood flow were found with each treatment. These results demonstrate that improvements in LM can be achieved immediately following hospital discharge and 6 months post‐burn without alterations to basal muscle protein turnover. Early and late outpatient RET are effective methods to augment muscle mass following severe burn injury.Grant Funding Source: Supported by NIDRR grant H133A120091; NIH P50 GM060388, R01 HD049471, R01 GM056687

Severe thermal trauma alters adipose tissue mitochondrial function in children

Severe thermal trauma results in a hypermetabolic stress response. Whether altered mitochondrial function plays a role in this response remains unknown. Here, coupled and uncoupled mitochondrial O2 consumption rates (Mito‐VO2) were determined in subcutaneous adipose tissue (AT) samples obtained from healthy children and children with severe burns.Maximal Mito‐VO2 was determined in Digitonin permeabilized subcutaneous AT samples from healthy children (7.8±2.3 years old, n=5), and children with severe burns (12.1±2.4 years old, 42±28 days post‐burn, 55±17% total body surface area burned, n=9) (mean±SD), in the presence of excess substrates (octanoyl‐carnitine, pyruvate, malate, glutamate, and succinate) and ADP. State 4 respiration was determined following the addition of oligomycin.Mito‐VO2 was 2.5‐fold greater in AT samples from children with severe burns relative to healthy children (2.04±0.34 vs. 0.79±0.23 pmol/(mg*sec), P<0.05). In addition, AT state 4 respiration (when Mito‐VO2 is uncoupled from ATP production) was 5‐fold greater in severely burned children relative to healthy children (2.06±0.39 vs. 0.42±0.15 pmol/(mg*sec), P<0.05) (mean±SEM).These data are the first to show that severe burn injury alters subcutaneous AT mitochondrial function; where mitochondria have a greater capacity for uncoupled respiration in patients with severe burns. This suggests that altered AT mitochondrial function may play a role in the hypermetabolic response to burn injury.Supported by the National Institutes of Health grant P50‐GM60338 and Shriners Hospitals for Children grants 84090 and 84080.

The US Army burn center

Renz, Evan M. MD; King, Booker T. MD; Chung, Kevin K. MD; White, Christopher E. MD; Lundy, Jonathan B. MD; Lairet, Kimberly F. MD; Maani, Christopher F. MD; Young, Alan W. DO; Stout, Louis R. MSN; Chan, Rodney K. MD; Wolf, Steven E. MD; Baer, David G. PhD; Cancio, Leopoldo C. MD; Blackbourne, Lorne H. MD Author Information

Gut Mucosal Homeostasis and Cellular Mediators after Severe Thermal Trauma and the Effect of Insulin-Like Growth Factor-I in Combination with Insulin-Like Growth Factor Binding Protein-3

Increased small bowel epithelial cell apoptosis and decreased cell proliferation lead to impairment of gut mucosal integrity and function after thermal injury. Impairment of gut integrity is associated with increased bacterial translocation and incidence of sepsis. The purpose of this study was to determine whether IGF-I/IGF binding protein (IGFBP)-3 can improve small bowel homeostasis after injury and by which cellular mechanisms these changes occur and to identify changes in apoptosis-related genes after burn and the effect of bile acid on small bowel epithelial cell apoptosis after burn. Rats sustained a thermal injury and received saline or the IGF-I/IGFBP-3 complex. Serum and small intestine were taken at 1, 2, 5, and 7 d after injury and serum inflammatory cytokines and mucosal apoptosis, proliferation, villous morphology, and apoptotic and proliferative mediators were measured. Apoptosis-related gene expression and the bile acid pool were determined in separate experiments up to 6 h after burn. Gut epithelial cell apoptosis as well as apoptosis-related genes were increased after the thermal injury, whereas bile acid secretion was significantly decreased (P < 0.05). IGF-I/IGFBP-3 significantly improved villous height and cells per villous by decreasing small bowel epithelial cell apoptosis and increasing proliferation (P < 0.05). Decreased apoptosis was associated with decreased Fas, Fas-ligand, and TNF when compared with saline (P < 0.05). A severe thermal injury caused an up-regulation of apoptosis and apoptosis-related genes and down-regulation of bile acid secretion. IGF-I/IGFBP-3 decreases small bowel epithelial cell apoptosis through down-regulation of the Fas pathway, which improves gut mucosal integrity after a severe thermal injury.

A Suppressor-Inducer Factor Produced by Burn Trauma-Associated T Cells

Six days after a full-thickness scald burn in specific-pathogen free mice, potent suppressive activity was observed in the serum and in supernatants of splenic T cells. The serum activity could be blocked by addition of a monoclonal anti-T suppressor molecule antibody to assay cultures. An examination of the six-day postburn T cell supernatants revealed suppressor inducer T cell (Tsi) activity with a number of characteristics of other Tsi factors described in other systems. These observations further implicate the suppressor T cell pathway in the immunoregulatory sequelae of severe thermal trauma.

Maintenance of oxygen transport in severe thermal trauma

Maintenance of oxygen transport in severe thermal trauma

Liver function following thermal injury.

Studies of acute changes in hepatic function utilizing the hepatic clearances of rose bengal (I131) and uric acid, and the determination of relative splanchnic oxygen consumption were performed in dogs following a 22 cal/cm2 30% body surface area burn in an attempt to determine the etiology of the hepatic pathologic changes which have been shown to occur following thermal injury. Although rose bengal clearance decreased following injury, arterial-hepatic venous oxygen difference rose sufficiently to increase relative splanchnic oxygen consumption. Plasma uric acid concentration increased following the burn but the arterial-hepatic venous uric acid difference indicated that the changes were not necessarily a result of hepatic dysfunction but could be explained on the basis of accelerated purine catabolism. The postburn administration of morphine effected a significant decrease in the relative splanchnic oxygen consumption. The infusion of dextran did not increase rose bengal clearance proportionate to the resulting increase in plasma volume. The data indicate that hepatic hypoxia does not contribute to the production of early hepatic injury following severe thermal trauma.