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Exposure to high energy impulse noise (BLAST) caused by explosions, result in structural and functional damage to the hollow organs, especially to the respiratory and auditory systems. Lung damage includes alveolar wall rupture, edema and hemorrhage, and may be fatal. Previous observations at the molecular level using the rat model, suggested that secondary free radical-mediated oxidative stress occurs post exposure resulting in antioxidant depletion and hemoglobin (Hb) oxidation. This study examined whether a short period of pre-exposure supplementation with antioxidants would protect Hb from the effects of BLAST exposure. Six groups of male Sprague-Dawley rats (8/group) were gavaged with 800 IU vitamin E (VE) in 2 ml corn oil, 1000 mg vitamin C (VC) in 2 ml distilled water or 25 mg or (-lipoic acid (LA) in 2 ml corn oil for 3 days. Matched control groups were gavaged with the respective vehicles. On day 4, rats were deeply anesthetized and exposed to a simulated BLAST wave with an average peak pressure of 62 +/- 2 kPa. Rats were euthanized one hour post exposure and blood samples were obtained by cardiac puncture and analyzed using a hemoximeter. Post exposure oxygenation states (HbO2, O2 saturation, and O2 content) were markedly decreased, while reduced-Hb was increased. Supplementation with VE and LA reversed the trend and increased Hb oxygenation, but VC did not. This suggests that a brief dietary loading with pharmacological doses of VE or LA, but not VC shortly before BLAST exposure may be beneficial. Moreover, measurement of blood oxygenation may function as a simple semi-invasive biomarker of BLAST-induced injury applicable to humans.

To study the effect of hypertonic saline solution on the rheology and putative mechanism, we investigated the changes of plasma viscosity, blood viscosity and reduced viscosity in dogs treated with hypertonic saline solution after burn-blast combined injury and observed the effect of hypertonic saline solution therapy on the viscoelastic property of erythrocyte membranes measured by micropippette aspiration technique in rats with burn. The results showed that the blood viscosity and reduced viscosity increased significantly in dogs after injury, and plasma viscosity also increased significantly at 24 h after injury. Elastic moduli and viscous coefficients of erythrocyte membranes increased obviously in rats after burn. The hypertonic saline solution therapy could significantly improve blood viscosity and reduced viscosity, but it did not significantly improve elastic moduli and viscous coefficients of erythrocyte membranes. These suggested that the hardness of erythrocyte membranes increased, the deform property of erythrocyte membranes decreased, and the blood rheology became worse after burn blast combined injury. Hypertonic saline solution therapy could significantly improve the blood rheology. The effect did not bear a significant relationship with the change of single biomechanics property of erythrocyte membranes. It might be related with other factors.

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.

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.

The plasma concentrations of glucose, adrenaline, noradrenaline, insulin, and cortisol were measured in 59 patients within 18 hours of military gunshot/missile (MG/M) wound. The wounds were categorized by the Red Cross Wound Classification (RCWC) and assessed by the Injury Severity Score (ISS) method. The majority of the measured biochemical parameters, except insulin, were significantly increased after MG/M wounds, compared with control values. Plasma glucose concentration in wounded patients was positively related to ISS over the whole severity range. Plasma insulin concentration increased with glucose. Noradrenaline and cortisol were positively related to glucose. Because hemorrhage is the most common cause of general response to MG/M wound, we concluded that glucose measurement could be a useful adjunct tool to the RCWC in rapid and accurate assessment of severely wounded patients, especially those with occult thoraco-abdominal wounds.

Plasma amino acid profiles in patients during the early period (first 18 hours) following military gunshot/missile wounds were investigated. Patients (n = 29) were casualties from the war in the former Yugoslavia with injury severity scores ranging from 4 to 18. They were divided into three groups: soft tissue (muscle) damage, wounds with fractures, and vital structures injured. Controls were normal blood donors (n = 17). Free amino acids were analyzed in venous plasma. Increased concentrations of phenylalanine and glutamine associated with increased molar phenylalanine/tyrosine ratio in plasma indicated increased net protein catabolism in the peripheral tissues, regardless of the type of injured tissues. Decreased plasma arginine, ornithine and citrulline levels, accompanied with increased molar glutamine/valine ratio, suggested disturbance in urea cycle activity, although urea level was not altered. We concluded that early changes in plasma amino acid pool characteristics after wounds were of systemic origin, not related to the type of injured tissues.

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.

Fifty male mongrel dogs were inflicted with 25% III degree burn combined with moderate blast injury. They were divided into five groups; four treatment groups (with various amounts of infused fluid and sodium) and one control group. Each group consisted of 10 animals. The results indicated that every kind of treatment was effective. However, the regime of crystalloid plus whole blood (infused 8 h after injury) was the best. Generally speaking, fluid therapy should be given carefully. The optimal amount of sodium given was 0.3 mmol.kg-1.1%.BSA-1. The amount of water-2-2.5ml.kg-1% BSA-1. After treatment with the Parkland formula, the pulmonary water content was high, so it is not worth recommending. Continuous measurement of the viscosity of plasma, microhematocrit and the amount of sodium in urine and blood were simple and useful.

Hematologic evaluation of an individual with an initial systemic body burden of approximately 200 mu Ci 241Am revealed a significant (P less than 0.01) reduction of total leukocytes, neutrophils and lymphocytes. This effect on total leukocytes and neutrophils was evident approximately 30 days after exposure, appeared to stabilize at about 3 months after exposure, and remained at this lower level through a 52-month observation period. The effect on lymphocytes was apparent by 3 days after exposure, stabilizing at approximately 50% of pre-exposure values for about 7 months, with a return to pre-exposure levels in the following 4 yr. There was a progressive and significant (P less than 0.001) decline in platelet counts during the 52-month post-exposure period. The pattern of response in erythrocyte parameters was complex. Immediately after the accident, these values were less than the pre-exposure mean level; they gradually increased (P less than 0.001) for approximately 2 yr and then began a progressive decline (P less than 0.001).