Aim. To evaluate the temporal changes in circulating cytokines rallying systemic inflammatory response after a blast injury.Material and Methods. Experiments were performed on 60 male Wistar rats (50 rats with blast-related soft tissue injury of the thigh and 10 intact rats). Blast injury was modeled under general anaesthesia using grater firecrackers stuffed with a pyrotechnic mixture. After 3, 7, 14 and 28 days post injury, we carried out a gross examination of the wound and its drainage, measured wound area, assessed local oedema severity, and evaluated serum potassium, myoglobin TNF-α, IL-1β, IL-6, and IL-10.Results. Three to seven days post injury, therewas abundant serous and purulent exudate and pronounced local edema without considerable changes in the wound area. Serum myoglobin and potassium were raised 2.2-2.6-fold and 1.3-fold, respectively (p < 0.05); in addition, we documented the elevation of a major pro-inflammatory cytokine IL-1β. Fourteen days post injury, wound area reduced by 24%, (p < 0.05) along with the decreased wound drainage and local edema of the injured area. Although the levels of serum myoglobin and pro-inflammatory cytokines (in particularIL-6) lowered, they were still significantly higher as compared with the intact rats. Twenty eight days post injury, fibrosis has been completed, epithelialization occurred and only a small scab remained on the wound surface. Yet, serum IL-1β still was 1.3-fold higher than in the intact animals (p < 0.05), albeit IL-6 and TNF-α returned to the reference values. The concentration of anti-inflammatory cytokine IL-10 reached its maximum values relative to the control (3.9-fold, p < 0.05) to the 14th day post injury that was followed by a considerable reduction (though not reaching the reference values) by the period of scar formation.Conclusion. Blast injury in rats is accompanied by a dysregulated balance between pro-inflammatory and anti-inflammatory cytokines throughout all regeneration phases.

Regional activation of cellular repair systems, including local application of hyaluronic acid, is a promising direction for the sanogenesis of muscle injuries. Purpose: to identify the sanogenetic and pharmacological effects of local application of hyaluronic acid in experimental soft tissue compression trauma. Compression injury was simulated by mechanical compression of the right pelvic limb of a rat at the level of the lower leg for 7 hours with a pressure force of 10-12 kg/cm2. Further, the animals were divided into 2 groups: 3 hours after decompression, animals in the main group were injected with 3.5% hyaluronic acid (the drug «Hyalift 3.5») by fan-pricking with a sterile disposable syringe at 5-6 points to a depth of 0.5-0.8 cm in a volume of up to 0.1 ml at each point; rats in the control group were given a similar method and an equivalent volume of 0.9% sodium chloride solution. The level of myoglobin in the blood, microcirculation, histomorphological and immuno- histochemical characteristics of tissues in the compression area were studied. A comprehensive analysis of the results of the study allowed us to establish that early local administration of 3.5% hyaluronic acid to the area of compression damage of soft tissues (3 hours after decompression) has a muscle-protecting effect, activates the repair system of damaged skeletal muscles. It is concluded that the sanogenetic effect of hyaluronic acid is mediated by the mecha- nisms of its pharmacological action: activation of angiogenesis, improvement of in situ efficiency of microcirculation and metabolism, reduction of the severity of primary and secondary necrosis and about traumatic disorders, activation of regeneration of damaged muscle fibers with the formation of muscle tissue. Hyaluronic acid is an active stimulant of reparative processes in the perspective of pharmacotherapy and may be a promising component in the local correction of extensive traumatic injuries.

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Background. The possibility of local application of autologous blood plasma (ABP) in soft tissue injuries is currently of particular interest.Objectives. Evaluation of the effects of peri-wound (perifocal) administration of ABP on red blood parameters, microcirculation and oxygen supply of soft tissues of the limb in experimental explosive wound (EW) in rats.Methods. EW was simulated on male Wistar rats (n=146) using a firecracker with a pyrotechnic mixture (patent RU No. 2741238 dated 22.01.2021). Animals were divided into 4 groups: control (2), comparison (1), main (1). The volume of blood loss in explosive wounds was 8 and 15% of the estimated circulating blood volume (CBV) of the animal. Blood was drawn from the rat tail to obtain ABP. 3 hours after the injury, ABP or 0.9% sodium chloride solution was injected intramuscularly into the explosive wound area at a rate of 2.0 ml/kg of animal weight. After 3, 7, 14, 28 days, the number of red blood cells, haemoglobin content, haematocrit were determined in the blood, and microcirculation and oxidative metabolism parameters were determined in the skeletal muscles of the injured area. The data were processed using Microsoft Excel 2013 (Microsoft, USA) and Statistica 10.0 (StatSoft Inc., USA).Results. Blood loss of 8% of the CBV in injured animals did not lead to changes in the quantitative composition of peripheral red blood. After an explosive wound with a blood loss of 15% of the CBV, there was a moderate decrease in the number of red blood cells (from 8.3×1012/l to 6.5×1012/l, p < 0.02), haemoglobin level (from 149.5 g/l to 118 g/l, p < 0.01), haematocrit (from 43.8% to 33.6%, p < 0.01) with recovery by day 7 of observation. The explosive soft tissue wound was characterized by marked post-traumatic microcirculatory disorders irrespective of the amount of blood loss. Perifocal intramuscular administration of ABP in animals with an explosive wound and blood loss of 15% CBV reduced the severity of post-traumatic microcirculatory and oxidative metabolic disorders mainly in the early post-traumatic period, as evidenced by an increase in the perfusion variation coefficient Kv by 1.2–1.3 times (p < 0.05), tissue oxygen consumption U by 20–22% (p < 0.05) and fluorescent oxygen consumption by FPC by 48% (p < 0.05).Conclusion. With an experimental explosive wound of the soft tissues of the thigh in rats, a single early (3 hours after the injury) peri-wound intramuscular administration of ABP reduces the severity of local post-traumatic microcirculatory and metabolic disorders in skeletal muscle.

Relevance. In emergency situations, cases of crush syndrome with extensive ischemic damage of soft tissues often occur due to prolonged compression from damaged buildings, structures, rocks, damaged transport, mines, etc. Unmet medical need for providing care to victims with severe compression trauma determines the importance of research on the development of new pathogenetically justified treatments of postischemic disorders. The positive role of multipotent mesenchymal stromal cells has been proved in the process of posttraumatic regeneration of skeletal muscles. Intention. To reveal morphological features of skeletal muscles in severe compression trauma after the introduction of multipotent mesenchymal stromal cells in the hyaluronic acid gel into the damaged tissues. Methods. The object of the study was an experimental model of a continuous (7hour) static compression (squeezing force 10-12 kg/cm 2) of the soft tissues of the hip by metal vices in sexually mature white outbred male rats with body mass of 300-340 g. Three hours after the vices removal, rats in the experimental group received a single fanshaped injection of suspended cultured multipotent mesenchymal stromal cells of human adipose tissue (1.5 • 10 6 cells) in 0.5 ml of 1.75 % hyaluronic gel solution (Aestetic Dermal S.L., Spain) intramuscularly into the compression region. Control animals under similar conditions were injected with an 0.9 % solution of sodium chloride. For reference parameters, biomaterial from intact rats was used. In 7, 14 and 28 days after decompression by the lightoptical method, the histological sections of the biomaterial from the compression region were examined. Results and Discussion. It has been established that implantation of cultured multipotent mesenchymal stromal cells in soft tissues damaged by mechanical compression contributes to an early reduction of necrobiotic changes in the zone of muscle compression, accelerated recovery of microcirculation and reparative regeneration of muscle fibers with an active new growth of muscle tissue. Seven, 14 and 28 days after exposure, the relative area of muscle fibers was 23 35.6 % (p<0.05) higher than in control animals and achieved 62.4-85.6 %. Conclusion. It has been suggested that cultured multipotent mesenchymal stromal cells in a cellular carrier locally transplanted into the lesion region can be considered as a fruitful way to create effective concentrations of interstitial growth factors and cytokines that regulate severity of the inflammatory reaction, angiogenesis and reparative processes resulted from massive mechanical compression of soft tissues.