Gas explosion-induced acute blast lung injury assessment and biomarker identification by a LC-MS-based serum metabolomics analysis.

The objective of this study was to evaluate the histopathological effect of gas explosion on rats, and to explore the metabolic alterations associated with gas explosion-induced acute blast lung injury (ABLI) in real roadway environment using metabolomics analyses. All rats were exposed to the gas explosion source at different distance points (160 m and 240 m) except the control group. Respiratory function indexes were monitored and lung tissue analysis was performed to correlate histopathological effect to serum metabolomics. Their sera samples were collected to measure the metabolic alterations by ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). HE staining in lung showed that the gas explosion caused obvious inflammatory pulmonary injury, which was consistent with respiratory function monitoring results and the serum metabolomics analysis results. The metabolomics identified 9 significantly metabolites different between the control- and ABLI rats. 2-aminoadipic acid, L-methionine, L-alanine, L-lysine, L-threonine, cholic acid and L-histidine were significantly increased in the exposed groups. Citric acid and aconitic acid were significantly decreased after exposure. Pathway analyses identified 8 perturbed metabolic pathways, which provided novel potential mechanisms for the gas explosion-induced ABLI. Therefore, metabolomics analysis identified both known and unknown alterations in circulating biomarkers, adding an integral mechanistic insight into the gas explosion-induced ABLI in real roadway environment.

Evaluation of Gas Explosion Injury Based on Analysis of Rat Serum Profile by Ultra-Performance Liquid Chromatography/Mass Spectrometry-Based Metabonomics Techniques.

Gas explosion can lead to serious global public health issues. Early period gas explosion injury (GEI) can induce a series of histopathologic and specific metabolic changes. Unfortunately, it is difficult to treat GEI thoroughly. To date, the specific molecular mechanism of GEI is still unclear. To accurately diagnose and provide comprehensive clinical intervention, we performed a global analysis of metabolic alterations involved in GEI. The physiological and behavioral indicators' changes of rats after gas explosion were observed. These metabolic alterations were first investigated in a rat model using serum metabonomics techniques and multivariate statistical analysis. Significant heart rate (HR), mean blood pressure (mBP), and neurobehavioral index changes were observed in the GEI group after gas explosion. UPLC-MS revealed evident separated clustering between the control and GEI groups using supervised partial least squares discriminant analysis (PLS-DA). We designed an integrated metabonomics study for identifying reliable biomarkers of GEI using a time-course analysis of discriminating metabolites in this experiment. The metabonomics analysis showed alterations in a number of biomarkers (21 from serum). The meaningful biomarkers of GEI provide new insights into the pathophysiological changes and molecular mechanisms of GEI, including the disturbances in oxidative stress and neuroinflammatory reaction, as well as in metabolism of lipids, glucose, and amino acids in rats, suggesting that the process of GEI in humans is likely to be comprehensive and dynamic. Correlations between the GEI group and the biomarkers identified from the rat model will be further explored to elucidate the metabolic pathways responsible for GEI in the human body.

The abnormalities of coagulation and fibrinolysis in acute lung injury caused by gas explosion.

Acute lung injury (ALI) caused by gas explosion is common, and warrants research on the underlying mechanisms. Specifically, the role of abnormalities of coagulation and fibrinolysis in this process has not been defined. It was hypothesized that the abnormal coagulation and fibrinolysis promoted ALI caused by gas explosion. Based on the presence of ALI, 74 cases of gas explosion injury were divided into the ALI and non-ALI groups. The results of prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), and platelet count (PLT) were collected within 24 hours and compared between the groups. ALI models caused by gas explosion were established in Sprague Dawley rats, and injuries were evaluated using hematoxylin and eosin (HE) staining and histopathological scoring. Moreover, the bronchoalveolar lavage fluid (BALF) was collected to examine thrombin-antithrombin complex (TAT), tissue factor (TF), tissue factor pathway inhibitor (TFPI), and plasminogen activator inhibitor-1 (PAI-1) levels by enzyme-linked immunosorbent assay (ELISA). The patients in ALI group had shorter PT and longer APTT, raised concentration of FIB and decreased number of PLT, as compared to the non-ALI group. In ALI rats, the HE staining revealed red blood cells in alveoli and interstitial thickening within 2 hours which peaked at 72 hours. The levels of TAT/TF in the BALF increased continually until the seventh day, while the PAI-1 was raised after 24 hours and 7 days. The TFPI was elevated after 2 hours and 24 hours, and then decreased after 72 hours. Abnormalities in coagulation and fibrinolysis in lung tissues play a role in ALI caused by gas explosion.

Exosomal neurofilament light: A prognostic biomarker for remote symptoms after mild traumatic brain injury?

OBJECTIVE: To measure exosomal and plasma levels of candidate blood biomarkers in veterans with history of mild traumatic brain injury (mTBI) and test their relationship with chronic symptoms. METHODS: Exosomal and plasma levels of neurofilament light (NfL) chain, tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-10, and vascular endothelial growth factor (VEGF) were measured using an ultrasensitive assay in a cohort of 195 veterans, enrolled in the Chronic Effects of Neurotrauma Consortium Longitudinal Study. We examined relationships between candidate biomarkers and symptoms of postconcussive syndrome (PCS), posttraumatic stress disorder (PTSD), and depression. Biomarker levels were compared among those with no traumatic brain injury (TBI) (controls), 1-2 mTBIs, and repetitive (3 or more) mTBIs. RESULTS: Elevated exosomal and plasma levels of NfL were associated with repetitive mTBIs and with chronic PCS, PTSD, and depression symptoms. Plasma TNF-α levels correlated with PCS and PTSD symptoms. The total number of mTBIs correlated with exosomal and plasma NfL levels and plasma IL-6. Increased number of years since the most recent TBI correlated with higher exosomal NfL and lower plasma IL-6 levels, while increased number of years since first TBI correlated with higher levels of exosomal and plasma NfL, as well as plasma TNF-α and VEGF. CONCLUSION: Repetitive mTBIs are associated with elevated exosomal and plasma levels of NfL, even years following these injuries, with the greatest elevations in those with chronic PCS, PTSD, and depression symptoms. Our results suggest a possible neuroinflammatory and axonal disruptive basis for symptoms that persist years after mTBI, especially repetitive.

CD28 deficiency attenuates primary blast-induced renal injury in mice via the PI3K/Akt signalling pathway.

INTRODUCTION: Primary blast affects the kidneys due to direct shock wave damage and the production of proinflammatory cytokines without effective treatment. CD28 has been reported to be involved in regulating T cell activation and secretion of inflammatory cytokines. The aim of this study was to investigate the influence of primary blast on the kidney and the effect of CD28 in mice. METHODS: A mouse model of primary blast-induced kidney injury was established using a custom-made explosive device. The severity of kidney injury was investigated by H&E staining. ELISA was applied to study serum inflammation factors' expression. Western blot assays were used to analyse the primary blast-induced inflammatory factors' expression in the kidney. Immunofluorescence analysis was used to examine the PI3K/Akt signalling pathway. RESULTS: Histological examination demonstrated that compared with the primary blast group, CD28 deficiency caused a significant decrease in the severity of the primary blast-induced renal injury. Moreover, ELISA and western blotting revealed that CD28 deficiency significantly reduced the levels of interleukin (IL)-1ß, IL-4 and IL-6, and increased the IL-10 level (p<0.05). Finally, immunofluorescence analysis indicated that PI3K/Akt expression also changed. CONCLUSIONS: CD28 deficiency had protective effects on primary blast-induced kidney injury via the PI3K/Akt signalling pathway. These findings improve the knowledge on primary blast injury and provide theoretical basis for primary blast injury treatment.

Apoptotic mechanisms in rabbits with blast-induced acute lung injury 1.

PURPOSE: To investigate the apoptotic mechanisms in rabbits with blast-induced acute lung injury (ALI). METHODS: A total of 40 rabbits were randomly divided into a blank control group (A, n=10) and an experimental group (EXP, n=30). Explosion-induced chest-ALI models were prepared and sampled at different time points (4, 12, and 24h after modeling, T1-T3) to test the lung dry weight/wet weight ratio (W/D) and arterial oxygen pressure (PaO2), apoptosis of lung tissue by the TUNEL assay, and Caspase-3, Bax, and Bcl-2 levels by immunohistochemical analysis. Furthermore, lung tissue was sampled to observe pathological morphology by microscopy. RESULTS: Under a light microscope, Group EXP exhibited obvious edema in the pulmonary interstitial substance and alveoli, a large number of red blood cells, inflammatory cells, and serous exudation in the alveolar cavity, as well as thickening of the pulmonary interstitial fluid. Compared to Group A, the W/D ratio was significantly increased in Group EXP (P<0.01), while PaO2 was significantly reduced (P<0.01). The apoptosis index was significantly increased (P<0.01), and caspase-3 and Bax/Bcl-2 levels were increased (P<0.01). CONCLUSION: Apoptosis plays an important role in the occurrence and development of acute lung injury in rabbits by participating in lung injury and promoting the progression of ALI.

Apoptotic mechanisms in rabbits with blast-induced acute lung injury

Abstract Purpose: To investigate the apoptotic mechanisms in rabbits with blast-induced acute lung injury (ALI). Methods: A total of 40 rabbits were randomly divided into a blank control group (A, n=10) and an experimental group (EXP, n=30). Explosion-induced chest-ALI models were prepared and sampled at different time points (4, 12, and 24h after modeling, T1-T3) to test the lung dry weight/wet weight ratio (W/D) and arterial oxygen pressure (PaO2), apoptosis of lung tissue by the TUNEL assay, and Caspase-3, Bax, and Bcl-2 levels by immunohistochemical analysis. Furthermore, lung tissue was sampled to observe pathological morphology by microscopy. Results: Under a light microscope, Group EXP exhibited obvious edema in the pulmonary interstitial substance and alveoli, a large number of red blood cells, inflammatory cells, and serous exudation in the alveolar cavity, as well as thickening of the pulmonary interstitial fluid. Compared to Group A, the W/D ratio was significantly increased in Group EXP (P<0.01), while PaO2 was significantly reduced (P<0.01). The apoptosis index was significantly increased (P<0.01), and caspase-3 and Bax/Bcl-2 levels were increased (P<0.01). Conclusion: Apoptosis plays an important role in the occurrence and development of acute lung injury in rabbits by participating in lung injury and promoting the progression of ALI.

Traumatic andropause after combat injury.

In association with lower extremity amputation, complex genitourinary injuries have emerged as a specific challenge in modern military trauma surgery. Testicular injury or loss has profound implications for the recovering serviceman, in terms of hormone production and future fertility. The initial focus of treatment for patients with traumatic testicular loss is haemostasis, resuscitation and management of concurrent life-threatening injuries. Multiple reoperations are commonly required to control infection in combat wounds; in a review of 300 major lower extremity amputations, 53% of limbs required revisional surgery, with infection the commonest indication. Atypical infections, such as invasive fungal organisms, can also complicate military wounding. We report the case of a severely wounded serviceman with complete traumatic andropause, whose symptomatic temperature swings were initially mistaken for signs of occult sepsis.

Changes of serum Tau, GFAP, TNF-α and malonaldehyde after blast-related traumatic brain injury.

OBJECTIVE: To determine the changes of serum Tau protein, glial fibrillary acidic protein (GFAP), tumor necrosis factor alpha (TNF-α), and malonaldehyde (MDA) in rats after blast-related traumatic brain injury (BTBI) and to provide relative information for further studies on BTBI mechanism and seek specific biomarkers for BTBI. METHODS: Ninety male Sprague-Dawley rats were randomly assigned into three groups: control group, moderate blast injury group, and severe blast injury group (n=30 for each). Rats in the moderate and severe blast injury groups were respectively exposed to corresponding levels of BTBI. After explosion, serum levels of Tau, GFAP, TNF-α, and MDA in each group were determined by Elisa assay at different time points after injury (8 h, 24 h, 3 d, and 6 d). The extent of brain damage was detected by Nissl staining and TUNEL assay. RESULTS: Serum levels of Tau and GFAP rapidly increased and reached the peak at 24 h after either moderate or severe blast injury. All the values were significantly higher than control group at all time points (P<0.05). Serum TNF-α level of both injury groups peaked at 8 h after BTBI and stayed significantly higher than control group at all time points (P<0.05). Serum MDA of two injury groups began to significantly increase at 3 d and the level stayed significantly higher than control group until 6 d (P<0.05). Moreover, unlike the other biomarkers, serum MDA of severe blast injury group was significantly higher than moderate blast injury group at 6 d (P<0.05). CONCLUSION: The changes of serum Tau, GFAP, and TNF-α showed a good sensitivity at the acute phase after BTBI (within 24 h). However, their specificity and correlation with the extent of injury were limited in this experiment. Moreover, although the change of serum MDA showed a poor sensitivity and specificity to the diagnosis of BTBI during the first few days, it can reflect the injury degree at 6 d after injury. Therefore, further studies are needed to improve the methods of detecting more serum markers and investigate the significance of multiple markers in diagnosing BTBI.

A novel model of burn-blast combined injury and its phasic changes of blood coagulation in rats.

Burn-blast combined injury has a complex pathological process that may cause adverse complications and difficulties in treatment. This study aims to establish a standard animal model of severe burn-blast combined injury in rats and also to investigate early phasic changes of blood coagulation. By using 54 Wistar rats, distance from explosion source (Hexogen) and size of burned body surface area were determined to induce severe burn-blast combined injury. Thereafter, 256 rats were randomly divided into four groups (n = 64): blast injury group, burn injury group, burn-blast combined injury group, and sham injury group. Gross anatomy and pathological changes in lungs were investigated at 3, 24, 72, and 168 h, respectively. Blood was also collected for analyzing coagulation parameters as prothrombin time, activated partial thromboplastin time, and plasma levels of fibrinogen, D-dimer, antithrombin III, and α2-antiplasmin from 0 to 168 h after injury. Severe burn-blast combined injury was induced by inflicting rats with a moderate blast injury when placing rats 75 cm away from explosion source and a full-thickness burn injury of 25% total body surface area. The rats with burn-blast combined injury had more severe lung injuries when compared with the other three groups. Pathological examination in the BBL group showed diffused alveolar hemorrhage, fluid filling, alveolar atelectasis, rupture and hyperplasia of partial alveolar septum, emphysema-like change, reduced capillary bed, and infiltration of extensive polymorphonuclear cells after injury. The blood of combined injured rats was in a hypercoagulable state within 24 h, shortly restored from 24 to 48 h, and rehypercoagulated from 48 to 72 h after injury. A secondary excessively fibrinolytic function was also found thereafter. The rat model of burn-blast combined injury was successfully established by simulating real explosion characteristics. Rats with burn-blast combined injuries suffered from more severe lung injuries and abnormal coagulation and fibrinolytic function than those induced by a burn injury or a blast injury component. Hence, a time-dependent treatment strategy on coagulation function should be emphasized in clinical therapy of burn-blast combined injury.

Inflammatory cytokine and chemokine expression is associated with heterotopic ossification in high-energy penetrating war injuries.

OBJECTIVE: Heterotopic ossification (HO) develops frequently after modern high-energy penetrating war injuries. The purpose of this prospective study was to identify and characterize the unique cytokine and chemokine profile associated with the development of HO as it pertained to the systemic inflammatory response after penetrating combat-related trauma. METHODS: Patients with high-energy penetrating extremity wounds were prospectively enrolled. Surgical debridement along with the use of a pulse lavage and vacuum-assisted-closure device was performed every 48-72 hours until definitive wound closure. Wound bed tissue biopsy, wound effluent, and serum were collected before each debridement. Effluent and serum were analyzed for 22 relevant cytokines and chemokines. Tissue was analyzed quantitatively for bacterial colonization. Correlations between specific wound and patient characteristics were also analyzed. The primary clinical outcome measure was the formation of HO as confirmed by radiographs at a minimum of 2 months of follow-up. RESULTS: Thirty-six penetrating extremity war wounds in 24 patients were investigated. The observed rate of HO in the study population was 38%. Of the 36 wounds, 13 (36%) demonstrated HO at a minimum follow-up of 2 months. An elevated injury severity score was associated with the development of HO (P = 0.006). Wound characteristics that correlated with the development of HO included impaired healing (P = 0.005) and bacterial colonization (P < 0.001). Both serum (interleukin-6, interleukin-10, and MCP-1) and wound effluent (IP-10 and MIP-1α) cytokine and chemokine bioprofiles were individually associated and suggestive of the development of HO (P < 0.05). CONCLUSIONS: A severe systemic and wound-specific inflammatory state as evident by elevated levels of inflammatory cytokines, elevated injury severity score, and bacterial wound colonization is associated with the development of HO. These findings suggest that the development of HO in traumatic combat-related wounds is associated with a hyper-inflammatory systemic response to injury. LEVEL OF EVIDENCE: Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.

Targeted resuscitation improves coagulation and outcome.

BACKGROUND: Acute trauma coagulopathy in seriously injured casualties may be initiated by tissue hypoperfusion. A targeted (or novel hybrid [NH]) resuscitation strategy was developed to overcome poor tissue oxygen delivery associated with prolonged hypotension. METHODS: Under the Animals (Scientific Procedures) Act 1986, terminally anesthetized large white pigs were divided into four groups (n = 6). Groups 1 and 2 received blast injury and 3 and 4 no blast (sham). All were given a controlled hemorrhage (35% blood volume) and an uncompressed grade IV liver injury. Five minutes later, all were resuscitated with 0.9% saline to a systolic arterial pressure (SAP) of 80 mm Hg. After 60 minutes, the NH groups (1 and 3) were resuscitated to a SAP (110 mm Hg), whereas hypotensive groups (2 and 4) continued with SAP 80 mm Hg for up to 8 hours from onset of resuscitation. RESULTS: Mean survival time was shorter in group 2 (258 minutes) compared with groups 1, 3, and 4 (452 minutes, 448 minutes, and 369 minutes). By the end of the study, hypotension was associated with a significantly greater prothrombin time (1.73 ± 0.10 and 1.87 ± 0.15 times presurgery, groups 2 and 4) compared with NH (1.44 ± 0.09 and 1.36 ± 0.06, groups 1 and 3, p = 0.001). Blast versus sham had no significant effect on prothrombin time (p = 0.56). Peak levels of interleukin 6 were significantly lower in NH groups. Arterial base excess was significantly lower with hypotension (-18.4 mmol/L ± 2.7 mmol/L and -12.1 mmol/L ± 3.2 mmol/L) versus NH (-3.7 mmol/L ± 2.8 mmol/L and -1.8 mmol/L ± 1.8 mmol/L, p = 0.0001). Hematocrit was not significantly different between groups (p = 0.16). CONCLUSION: Targeted resuscitation (NH) attenuates the development of acute trauma coagulopathy and systemic inflammation with improved tissue perfusion and reduced metabolic acidosis in a model of complex injury. This emphasizes the challenge of choosing a resuscitation strategy for trauma patients where the needs of tissue perfusion must be balanced against the risk of rebleeding during resuscitation.

Serum neutrophil gelatinase-associated lipocalin in ballistic injuries: a comparison between blast injuries and gunshot wounds.

UNLABELLED: Neutrophil gelatinase-associated lipocalin (NGAL) is part of a functionally diverse family of proteins that generally bind small, hydrophobic ligands. Neutrophil gelatinase-associated lipocalin is expressed in a number of human tissues including gastrointestinal, respiratory, and urinary tracts and tends to rise in response to inflammation. For this reason, we hypothesized that levels of NGAL might be expressed at higher levels after blast injury compared with other ballistic injury. PURPOSE: The purpose of this study is to test the hypothesis that NGAL may be a marker of injury severity in blast injury. MATERIALS: Twenty-three combat casualties (13 blast, 10 gunshot wounds) admitted to the multinational role 3 facility in Helmand province were studied. Serum NGAL was measured using a Biosite Triage point-of-care monitor at 5 time points after injury. RESULTS: Neutrophil gelatinase-associated lipocalin rose in both groups of casualties and was significantly predictive of death or renal failure at intensive care unit admission, 12 and 24 hours after injury. CONCLUSIONS: Neutrophil gelatinase-associated lipocalin is not a specific marker of blast injury but is predictive of both renal failure and poor outcome.

Effects of hypothalamus destruction on the level of plasma corticosterone after blast injury and its relation to interleukin-6 in rats.

Hypothalamus-pituitary-adrenal (HPA) axis is involved in the modulation of the innate immune response. The purpose of this study was to evaluate the dynamic relationship between plasma corticosterone and interleukin-6 in the hypothalamus-destroyed rats after blast injury. A total of 105 Sprague-Dawley rats were divided randomly into normal control (normal), sham operated (sham), blast injury plus sham operated (blast injury) and blast injury plus hypothalamus destruction groups. Symmetric electrolytic bilateral destruction of the hypothalamus was performed for the deeply anesthetic rats under sterile conditions. Seven days after the destruction of the hypothalamus, the animals were succumbed to moderate blast injury using a BST-I bioimpact machine. Plasma corticosterone and IL-6 levels were determined by radioimmunoassay and enzyme-linked immunosorbent assay, respectively. After blast injury, the corticosterone level in the hypothalamus-destroyed rats was significantly lower than that in the rats without destruction of hypothalamus at 3h (P<0.01) or from 5 to 8h (P<0.05). Reduction of corticosterone may be intrinsically correlated with the severe tissue injury and increased mortality (4/15 vs. 0/15, P<0.05). Circulating IL-6 level was markedly elevated in response to blast injury and hypothalamus destruction further increased IL-6 secretion (P<0.05). We concluded that elevation of pro-inflammatory IL-6 secretion might compensate the impaired HPA axis function after the trauma occurred in the hypothalamus-destroyed rats. These results also suggested that release of hypothalamus hormones is necessary to maintain certain magnitude of innate immunity after trauma.

[Blast injury]. / Das Explosionstrauma--Ein seltener, besonders schwieriger Fall.

The blast injury is characterized by 3 different patterns of injury: blast wave, splintered fragments and displacement of victim's body. Severe external and internal hemorrhage, tension pneumothorax and the lethal trios (hypothermia, acidosis, coagulopathy) require a rapid prehospital and inhospital trauma care according to a standardized protocol. The concepts of damage control resuscitation and damage control surgery have proven to be effective and should be integrated into the treatment.

Immune cytokine response in combat casualties: blast or explosive trauma with or without secondary sepsis.

The aim of this study was to assess the prognostic value of tumor necrosis factor (TNF) alpha, interleukin (IL)-8, IL-4, and IL-10 in combat casualties. Fifty-six casualties with severe trauma (blast and explosive) who developed sepsis and 20 casualties with the same severity of trauma without sepsis were enrolled in this study. Fifty-five casualties developed multiple organ dysfunction syndrome; 36 died. Blood was drawn on the first day of trauma. Concentrations of IL-8, TNF-alpha, IL-4, and IL-10 were determined in plasma using enzyme-linked immunosorbent assays. Mean values of IL-8 were 230-fold, IL-10 were 42-fold, and TNF-alpha were 17-fold higher in trauma and sepsis group (p < 0.01). Mean values of IL-8 were 60-fold, TNF-alpha were 43.5-fold, and IL-10 were 70-fold higher in the multiple organ dysfunction syndrome group (p < 0.01). Mean values of IL-8 were 2.3-fold and IL-10 were 1.4-fold higher in nonsurvivors and TNF-alpha were 2.2-fold higher in survivors (p < 0.01). IL-4 had no significance as a predictor of severity and outcome.

Recognizing, scoring, and predicting blast injuries.

The aim of this study was to find relevant signs and readily available parameters for the recognition of blast injuries and estimation of their severity. The injury severity, estimated by the Injury Severity Score (ISS), Red Cross Wound Classification (RCWC), and experimentally defined Pathology Scoring System for Blast Injuries (PSS/IS) according to Yelverton and modified for use in humans, was compared with a great number of subjective sensations, clinical signs, parameters of hemodynamic, metabolic, neuroendocrine and immune conditions. On the basis of these data, the confidence of the above-mentioned methods was analyzed in the evaluation of blast injuries. This study included 1303 casualties, wounded by explosive devices and with suspected blast injuries, treated at the Military Medical Academy in Belgrade (MMA) from 1991 to 1994. The patients were examined on admission at the MMA (<18 hours) and during hospitalization (1, 2, 5, and 7 days after wounding). The casualties with confirmed blast injury (n = 665, 51%) had an ISS ranging from 0 to 34 (mean 13) had wounds ranging from G1ST (soft tissue wounds caused by low energy transfer) to G3VF (massive wounds with fractures and injury of vital structures) according to the RCWC, with PSS/IS scores from 2 to 105 (mean 60). Statistically significant correlation was found between ISS and PSS/IS as well as RCWC and PSS/IS. Cytokines (IL-1, TNF|ga) and amino acids responded to a blast injury in similar manner as to gunshot wounds with a greater ISS or more severe RCWC injury type. The subjective sensations in blasted patients (deafness, thoracic pain, vertigo) and mediators, confirmed in previous experimental investigations as important factors in the pathogenesis of blast injuries (TxA2, sulfidopeptide leukotrienes) were relationed only to the PSS/IS.

A proposed biochemical mechanism involving hemoglobin for blast overpressure-induced injury.

Blast overpressure (BOP) is the abrupt, rapid, rise in atmospheric pressure resulting from explosive detonation, firing of large-caliber weapons, and accidental occupational explosions. Exposure to incident BOP waves causes internal injuries, mostly to the hollow organs, particularly the ears, lungs and gastrointestinal tract. BOP-induced injury used to be considered of military concern because it occurred mostly in military environments during military actions or training, and to a lesser extent during civilian occupational accidents. However, in recent years with the proliferation of indiscriminate terrorist bombings worldwide involving civilians, blast injury has become a societal concern, and the need to understand the biochemical and molecular mechanism(s) of injury, and to find new and effective methods for treatment gained importance. In general, past BOP research has focused on the physiological and pathological manifestations of incapacitation, thresholds of safety, and on predictive modeling. However, we have been studying the molecular mechanism of BOP-induced injury, and recently began to have an insight into that mechanism, and recognize the role of hemoglobin released during hemorrhage in catalyzing free radical reactions leading to oxidative stress. In this report we discuss the biochemical changes observed after BOP exposure in rat blood and lung tissue, and propose a biochemical mechanism for free radical-induced oxidative stress that can potentially complicate the injury. Moreover, we observed that some antioxidants can interact with Hb oxidation products (oxy-, met- and oxoferrylHb) and act as prooxidants that can increase the damage rather than decrease it.

Study on characteristics of blast-fragment combined injury in dogs.

It is known that blast wave and fragments are the primary causes of casualties from explosive weapons. To study the characteristics of blast-fragment combined injuries, functional and morphological changes were investigated in three groups of anesthetized dogs with blast injury, high velocity fragment extremity injury, and combined injuries of both types. The same parameters were also examined in a control group. Several of the functions investigated were systemic pressure, mean pulmonary arterial pressure (PAP), oxygenic partial pressure of arterial blood (Po2), thromboxane B2(TXB2), and 6-keto-prostaglandin F1 alpha (6-keto-PGF alpha). The morphologic study included gross, light microscopic, and transmission electronic microscopic observations. In the blast injury group, Po2 decreased and PAP, levels of blood plasma 6-keto-PGF alpha and level of TXB2 increased after injury, whereas PAP and level of 6-keto-PGF alpha decreased 24 hours after injury. The levels of 6-keto-PGF alpha and TXB2, in lung tissues, lung/body weight index were higher than those of the control group 24 hours after injury. The TXB2/6-keto-PGF alpha level in blood plasma increased slightly after injury, but showed no difference in lung tissue 24 hours after injury compared with the control group. The morphological changes showed that most of the animals sustained moderate lung injury. In the fragment injury group, Po2 decreased slightly and PAP increased slightly after injury; the levels of 6-keto-PGF alpha, TXB2 and TXB2/6-keto-PGF alpha in blood plasma increased after injury and were higher in lung tissue than in the control group 24 hours after injury. The lung/body weight index was nearly equal to that of control group. The morphological changes showed that only a few animals suffered from mild lung injury. In the combined injury group, Po2 and PAP changed in a manner similar to those of the other two injury groups but were more significantly. The level of blood plasma 6-keto-PGF alpha decreased gradually, whereas that of TXB2 increased permanently; thus, the levels of TXB2/6-keto-PGF alpha obviously increased after injury and were much higher than those in the other injury groups. The level of TXB2 in lung tissue was higher than that of the control group 24 hours after injury, but that of 6-keto-PGF alpha showed no change compared with that of the control group, and the level of TXB2/6-keto-PGF alpha was higher than in the other three groups. The morphological changes showed that most of animals sustained severe lung injury. It is concluded that extremity injury from high velocity fragment will aggravate lung blast injury. Changes in the levels of PGI2 and TXA2, can be used to determine the extent of injury in the three kinds of wounds. This may be useful for early diagnoses and rational treatment of the victims of explosion.

Interleukin-2 and interleukin-6 in relation to burn wound size in the acute phase of thermal injury.

Thermal injury induces significant physiologic responses of acute inflammation, acute phase reaction and cell repair and growth, mediated by interleukins, cytokines and growth factors. To determine the relative role of interleukin-2 (IL-2) and interleukin-6 (IL-6) in the acute phase of thermal injury, 60 patients (47 men and 13 women, with average age of 37 years [1.5 to 70.0 years]) were analyzed within the first 36 hours and at five to seven days postoperatively. The patient population was categorized by percent burn (2 or 3, or both, degrees): less than 20 percent, n = 22; 20 to 40 percent, n = 18, and greater than 40 percent, n = 20. The average percent burn was 32 percent (range 4 to 95 percent). The mechanism of injury was by flame (25 instances), explosion and flame (19 instances), scald (12 instances), electric (three instances) or chemical (one instance). Twelve patients had an associated inhalation injury; 14 patients had sepsis syndrome. The overall mortality rate was 13 percent. Within 36 hours of onset of injury, IL-6 and IL-2 levels increased in proportion to the severity of the burn wound size. IL-2 levels were significantly elevated in the 20 to 40 percent burn group as compared with the greater than 40 percent group and patients in a control group (p < 0.0001). IL-6 levels increased with burn wound size and were significant only in the greater than 40 percent group (p < 0.0007). Any physiologic modulation of the thermal injury by biologic modifiers must be adapted to the extent of burn wound size and phase of injury: acute, recovery or reparative for optimal benefit and results.