Features of the morphofunctional response of Peyer's patches in rats during the course of traumatic shock and the early post-shock period

The reaction of Peyer's patches to trauma manifests in: 1) vascular changes; 2) primary or stressor cells shifts recordable in traumatic shock, characterized by depletion of patch follicles by minor lymphocytes; 3) secondary changes associated with the onset of reparative processes; 4) the increased macrophagal activity detectable during the entire period of the traumatic shock and in the early post-shock period. It is suggested that changes seen may be due to endotoxin that penetrates from the intestine.     

Microcirculatory changes in the cheek pouch mucosa of hamsters in the dynamics of experimental traumatic shock]

Acute experiments conducted on hamsters demonstrated significant disturbances of the microcirculation in the mucosa of the cheek pouch during a severe traumatic shock after a standardized mechanical injury of the hip. All the animals died in the course of the first 24 hours after this trauma. If the animals died not earlier than in one hour after the trauma the microcirculation changes were distinctly phasic in character; particularly there was seen a phase of temporary relative adaptation and stabilization of the peripheral circulation, invariably followed by the phase of decompensation, the terminal phase and death. In cases with a rapid lethal issue in the course of one hour no distinct phasic character of the microcirculation changes was observed, but there was a more or less rapid aggravation of all he indices. In difference from the majority of other investigators, no marked intravascular erythrocyte aggregation was seen by the authors in the experiments described.     

Phenyl-T-Butyl-Nitrone is Active Against Traumatic Shock in Rats

Oxygen free-radicals appear to be involved in the pathogenesis of shock; therefore trapping of these radicals would modify the evolution of experimental shock. Experiments were performed on rats submitted to 100% lethal whole body trauma (rotating drum) and their survival, pathology, acid-base status and hematocrit level observed.

The spin trapping agent phenyl-t-butyl-nitrone (PBN) was administered before trauma (50, 100, 150 mg/kg i.p.) or at various intervals (30, 60 minutes) after establishment of a severe traumatic shock. It appeared that PBN administration was highly effective both in prevention and in reversion of traumatic shock in rats.     

Myeloperoxidase increased cardiomyocyte protein nitration in mice subjected to nonlethal mechanical trauma

Nonlethal mechanical trauma causes cardiomyocyte apoptosis which contributes to posttraumatic cardiac dysfunction. Apoptosis is positively correlated with protein nitration in the traumatic heart. However, the mechanisms responsible for the cardiomyocyte protein nitration remain unclear. The present study was designed to identify whether myeloperoxidase may contribute to protein nitration in nonlethal mechanical trauma and subsequent cardiomyocyte apoptosis, and, if so, to determine the possible mechanisms responsible. We used Noble-Collip drum to make nonlethal traumatic mice models. Male adult C57B16/J mice were placed in the Noble-Collip drum and subjected to a total of 200 revolutions at a rate of 40 r/min. Then myeloperoxidase activity and release, protein nitration, cardiomyocyte apoptosis, endothelial function and intercellular adhesion molecule-1 expression were determined. Nonlethal mechanical trauma was characterized by the 100% survival rate during the first 24 h after trauma, the lack of circulatory shock and without direct heart injury. However, myeloperoxidase activity significantly increased 6 h after trauma, and reached a maximum level 12 h after trauma. Obviously, protein nitration and cardiomyocyte apoptosis increased 12 h after trauma and could be blocked by administration of R15.7, a monoclonal antibody that blocks polymorphonuclear neutrophils adhesion. Moreover, endothelial dysfunction and intercellular adhesion molecule-1 upregulation were observed in traumatic mice. Our present study demonstrated for the first time that myeloperoxidase caused protein nitration and cardiomyocyte apoptosis in nonlethal traumatic mice. Inhibition of polymorphonuclear neutrophils adhesion and antinitration treatments may be novel measures in reducing posttraumatic cardiomyocyte apoptosis and secondary heart injury.     

Effects of dexamethasone on trace elements and serum protein patterns following brain trauma in rats

The effect of dexamethasone (Dxm) on trace elements and serum protein patterns was investigated in male Sprague-Dawley rats subjected to brain trauma. After 6-or 24 h of the traumatic incident, the level of serum copper was significantly higher in the Dxm-treated rats, compared to controls (p<0.05). The corresponding levels of zinc and iron did not show significant differences. The zinc level returned to normal 24 h after trauma. After 6 and 24 h of trauma, the sodium dodecyl sulfate (SDS)-polyacrylamide gel patterns of serum proteins showed that a 41.6-kDa protein was significantly increased in the Dxm-treated animals. Two proteins weighing 26.6 kDa and 55.1 kDa did not show Dxm-induced changes. These results suggest that increases in the copper-zinc ratio and the changes of the 26.6-kDa, 41.6-kDa, and 55.1-kDa proteins might be a useful prognostic indicator for severe traumatic brain injury.     

Salutary actions of nimodipine in traumatic shock

Nimodipine, a new calcium channel blocker, was found to prolong survival in a severely lethal form of traumatic shock in rats. Nimodipine, at infusion rates of 50 μg/kg/h also significantly limited the increase in circulating myocardial depressant factor (MDF) without significantly preventing the accumulation of the lysosomal protease, cathepsin D in the blood. Lower infusion rates were ineffective. Nimodipine did not stabilize lysosomal membranes directly in liver lysosomal suspensions, but was effective in preventing proteolysis in pancreatic homogenates. Nimodipine potentially prevents MDF formation by inhibiting proteases and probably by splanchnic vasodilation. Calcium channel blockers may be useful agents in the therapeutics of traumatic shock if given soon after the onset of the trauma.     

Mechanical traumatic injury without circulatory shock causes cardiomyocyte apoptosis: role of reactive nitrogen and reactive oxygen species

Apoptotic cell death plays a critical role in tissue injury and organ dysfunction under a variety of pathological conditions. The present study was designed to determine whether apoptosis may contribute to posttraumatic cardiac dysfunction, and if so, to investigate the mechanisms involved. Male adult mice were subjected to nonlethal traumatic injury, and cardiomyocyte apoptosis, cardiac function, and cardiac production of reactive oxygen/nitrogen species were determined. Modified Noble-Collip drum trauma did not result in circulatory shock, and the 24-h survival rate was 100%. No direct mechanical traumatic injury was observed in the heart immediately after trauma. However, cardiomyocyte apoptosis gradually increased and reached a maximal level 12 h after trauma. Significantly, cardiac dysfunction was observed 24 h after trauma in the isolated perfused heart. This was completely reversed when apoptosis was blocked by administration of a nonselective caspase inhibitor immediately after trauma. In the traumatized hearts, reactive nitrogen species (e.g., nitric oxide) and reactive oxygen species (e.g., superoxide) were both significantly increased, and maximal nitric oxide production preceded maximal apoptosis. Moreover, a highly cytotoxic reactive species, peroxynitrite, was markedly increased in the traumatic heart, and there was a significant positive correlation between cardiac nitrotyrosine content and caspase 3 activity. Our present study demonstrated for the first time that nonlethal traumatic injury caused delayed cell death and that apoptotic cardiomyocyte death contributes to posttrauma organ dysfunction. Antiapoptotic treatments, such as blockade of reactive nitrogen oxygen species generation, may be novel strategies in reducing posttrauma multiple organ failure.     

快速血型定型及交叉配血对创伤出血性休克患者抢救重要性的探讨

摘要 目的：通过对创伤出血性休克患者快速血型定型及交叉配血结果的分析,探讨其对创伤出血性休克患者抢救的重要性。方法：选择2018年2月至2020年2月于我院接受治疗的156例腹部创伤出血性休克患者为研究对象,对入组患者均实施快速血型鉴定及交叉配血,记录血型定型结果与交叉配血结果,对血型定型正反不一致,交叉配血结果不相合的数据进行分析。结果：156例入组患者实施快速血型定型显示有40例存在正反定型不一致,占比为25.64 %（40/156）,其中男性21例,占比52.50 %（21/40）,女性19例,占比47.50 %（19/40）,年龄分布10岁以下占比15.00 %,10~30岁占比37.50 %,31~60岁占比35.00 %,61岁及以上占比12.50 %,不同性别和年龄患者分布不具有统计学意义（P>0.05）;不规则抗体筛查阳性8例,检出率为5.13 %,其中男性2例占比25.00 %,女性6例占比75.00 %,有输血史7例占比87.50 %,无输血史1例占比12.50 %,比较显示女性明显高于男性,有输血史高于无输血史（P<0.05）;进行卡式交叉配血87例,其中有主侧相合而次侧不合2例,主侧不合次侧相合2例,在抢救用血过程中均采用配合性输血原则。156例患者经过快速血型定型及交叉配血,救治成功的有137例,成功率为87.82 %。结论：及时准确的血型定型及交叉配血对创伤出血性休克患者的救治具有重要意义,为创伤患者的输血救治提供有力保障,在临床上值得推广。     

Protective effects of CG-4203, a novel stable prostacyclin analog, in traumatic shock

We studied the effects of CG-4203, a novel stable prostacyclin analog, in a severe model of traumatic shock in rats. Traumatic shock was produced by Noble Collip drum trauma and was characterized by marked hypotension, a 4- to 5-fold increase in plasma cathepsin D and myocardial depressant factor activities, and survival time of 95 +/- 15 minutes. Treatment with CG-4203 (100 ng/kg/min) significantly prolonged survival time to 194 +/- 20 min (p less than 0.002). Traumatized rats treated with CG-4203 exhibited significantly lower plasma activities of the lysosomal hydrolase cathepsin D (p less than 0.05). Furthermore, the plasma accumulation of myocardial depressant factor (MDF) activity was also significantly blunted in traumatized CG-4203 treated rats when compared with traumatized rats receiving only the vehicle (p less than 0.01). Our results suggest that a combination of membrane stabilizing and anti-proteolytic effects and inhibition of platelet aggregation may mediate the protective effects of CG-4203 in traumatic shock.     

Acute and Prolonged Alterations in Brain Free Magnesium Following Fluid Percussion-Induced Brain Trauma in Rats

Abstract: Several studies have reported declines in brain total and free magnesium concentration after a traumatic insult to the CNS. Although the evidence suggests that this magnesium decline is associated with eventual neurologic outcome after trauma, the duration of free magnesium decline and its impact on related bioenergetic variables are relatively unknown. The present study has therefore used phosphorus magnetic resonance spectroscopy to determine the length of time that free magnesium remains suppressed after traumatic brain injury in rats. Immediately after the traumatic event, brain intracellular free magnesium declined to <60% of preinjury values and remained significantly depressed (50 ± 8%; p < 0.001) for 5 days before recovering to preinjury levels by day 8. Cytosolic phosphorylation ratio and mitochondrial oxidative capacity also significantly decreased ( p = 0.008) and increased ( p = 0.002), respectively, after trauma. However, unlike the time of maximum magnesium change, the maximum changes in these bioenergetic variables occurred at 16–24 h after trauma and thereafter remained stable until after the magnesium had recovered. We conclude that free magnesium decline after trauma precedes changes in bioenergetic variables. Furthermore, therapies targeted at reestablishing magnesium homeostasis after trauma may require administration over a 1-week period.     

DHEA: a novel adjunct for the treatment of male trauma patients

Despite significant advances in the management of trauma victims, traumatic injury with the ensuing sepsis and multiple organ failure remains the leading cause of death between the ages of 18 and 44 in the USA. Recently, interest in the clinically and experimentally observed gender dimorphic response to traumatic injury has led to the possibility of modulating cell and organ functions following trauma and hemorrhagic shock by the administration of sex steroids. Here, we review the effects of the adrenal steroid dehydroepiandrosterone (DHEA), a precursor of sex steroid synthesis, on organ and immune functions following trauma-hemorrhage, and its potential as a novel therapy for improving the depressed cell and organ functions in trauma patients.     

Traumatic shock causes elevation of the serotonin 5-HT2B receptor mRNA level in rat aorta

Previously we have shown that at traumatic shock in rats the force of contraction of isolated aorta in response to angiotensin II, vasopressin, endothelin 1, or norepinephrine is decreased. On the contrary, vasoconstriction caused by serotonin is increased. A possible reason of the alterations of neuroendocrine regulation of vascular tone in shock may be a change in the expression of the receptors of these agonists in blood vessels. In the present study, using real-time PCR, we demonstrated that a day after injury the contents of mRNA encoding receptors V1A for vasopressin, ETA for endothelin 1, and AT1 for angiotensin II are not changed in aorta. There was a slight increase of the serotonin 5-HT2A receptor mRNA (36 ± 16%; p = 0.41). The level of the 5-HT2B receptor mRNA in aorta, initially low (2% of the content of the mRNA of receptors 5-HT2A), after the injury increased 15.8 ± 0.3 times (p < 0.01). However, at traumatic shock there was no contraction of aorta in response to 5-HT2B receptor agonist BW723C86, while vasodilation of the isolated aorta preconstricted with norepinephrine in response to BW723C86 was similar to that of the vessel isolated from control rats. The data obtained suggest that the observed 5-HT2B receptor overexpression is not related to the increased serotonin-induced vasoconstriction and might cause other vascular pathological changes at traumatic shock.     

Decreased Autophagy Contributes to Myocardial Dysfunction in Rats Subjected to Nonlethal Mechanical Trauma

Autophagy is important in cells for removing damaged organelles, such as mitochondria. Insufficient autophagy plays a critical role in tissue injury and organ dysfunction under a variety of pathological conditions. However, the role of autophagy in nonlethal traumatic cardiac damage remains unclear. The aims of the present study were to investigate whether nonlethal mechanical trauma may result in the change of cardiomyocyte autophagy, and if so, to determine whether the changed myocardial autophagy may contribute to delayed cardiac dysfunction. Male adult rats were subjected to nonlethal traumatic injury, and cardiomyocyte autophagy, cardiac mitochondrial function, and cardiac function in isolated perfused hearts were detected. Direct mechanical traumatic injury was not observed in the heart within 24 h after trauma. However, cardiomyocyte autophagy gradually decreased and reached a minimal level 6 h after trauma. Cardiac mitochondrial dysfunction was observed by cardiac radionuclide imaging 6 h after trauma, and cardiac dysfunction was observed 24 h after trauma in the isolated perfused heart. These were reversed when autophagy was induced by administration of the autophagy inducer rapamycin 30 min before trauma. Our present study demonstrated for the first time that nonlethal traumatic injury caused decreased autophagy, and decreased autophagy may contribute to post-traumatic organ dysfunction. Though our study has some limitations, it strongly suggests that cardiac damage induced by nonlethal mechanical trauma can be detected by noninvasive radionuclide imaging, and induction of autophagy may be a novel strategy for reducing posttrauma multiple organ failure.     

Peculiarities of mitosis and nucleolar characteristics of the birch plantlets under antropogenous pollution

A study was made of some cytogenetic characteristics (mitotic activity, the level and spectrum of pathological mitosis, nucleolar features in root tip cells) in birch plantlets. The seeds were collected in four districts of Voronezh and in the ecologically clean territory. The index of mitotic activity has a considerable resistance to anthropogenous pollution. In the experimental areas, the level and spectrum of pathological mitosis increase. In contaminated areas we observed changes of nucleolar characteristics (the increased surface area of nucleoli and their higher number in cells, the increased number of cells with highly active types of nucleoli, the appearance of residual nucleoli). These changes can be considered as possible mechanisms of adaptation to stress due to antropogenous pollution. It is suggested that the use of such indices as single nucleolar surface area or the level of pathological mitosis may be perspective for cytogenetic monitoring of the environment, and for prognostification of environmental conditions suitable or unsuitable for the human health.     

Effect of enkephalins on the function of the calcium-regulating endocrine glands in shock

The experiments on white rats weighing 180-220 g have shown that in traumatic and hemorrhagic shock the initial increase in parathyroid hormone blood concentration is followed by the decrease of functional activity of parathyroid glands. Calcitonin concentration is found to increase during the first hours of shock. The changes in calcium-regulating gland function result in significant disturbances of calcium exchange during shock. The injection of synthetic leu-enkephalin analogs to rats with shock leads to normalization of calcium-regulating endocrine glands function.     

Proteomic profiling of the mesenteric lymph after hemorrhagic shock: Differential gel electrophoresis and mass spectrometry analysis

Experiments show that upon traumatic injury the composition of mesenteric lymph changes such that it initiates an immune response that can ultimately result in multiple organ dysfunction syndrome (MODS). To identify candidate protein mediators of this process we carried out a quantitative proteomic study on mesenteric lymph from a well characterized rat shock model. We analyzed three animals using analytical 2D differential gel electrophoresis. Intra-animal variation for the majority of protein spots was minor. Functional clustering of proteins revealed changes arising from several global classes that give novel insight into fundamental mechanisms of MODS. Mass spectrometry based proteomic analysis of proteins in mesenteric lymph can effectively be used to identify candidate mediators and loss of protective agents in shock models.     

Narrative Length and Speech Rate in Battered Women

Narrative length and speech rate of traumatic recollections have been previously associated with different emotions and adjustment trajectories after trauma. However, the evidence is limited and the results are mixed. The present study aimed to evaluate length (i.e., word count) and speech rate (i.e., words per minute) in narratives of events with different valence (i.e., neutral, positive, and negative/traumatic) by 50 battered women (trauma group) and 50 non-traumatized women (controls). The results showed that traumatic narratives by the trauma group were longer than those by the control group. Moreover, they were inversely related to time since the event and anxiety during disclosure, whereas the speech rate was also inversely associated with anxiety, as well as with peritraumatic dissociation and avoidance. The shorter narratives for positive events and a decelerated speech pattern for traumatic experiences predicted psychological symptoms. Additionally, the individual’s emotional state predicted narrative aspects, with bidirectional effects. Our findings showed that linguistic characteristics of traumatic narratives (but also of narratives of positive events) revealed information about how the victims elaborated autobiographical memories and coped with the trauma.     

Role of limbic structures in the mechanisms of post-traumatic epilepsy]

It was shown in the experiments on rats that intracerebroventricular administration of kainic acid (0.01, 0.05 microgram) after brain trauma, resulted in the occurrence of behavioral and electrographic convulsive disturbances; maximal expression of epileptic activity was obtained in entorhinal cortex and ventral hippocampus. Kainic acid induced epileptic reactions in nontraumatized rats only if injected in dose 0.1 microgram. Brain trauma did not lead to changes in seizures intensity induced by systemic picrotoxin administration. It is concluded that the formation of generator of pathologically enhanced excitation in limbic structures via increase of excitor glutamatergic neurotransmission is the important mechanism of traumatic epilepsy.     

A decreased frequency of sister chromatid exchanges in pregnant women

Sister chromatid exchanges (SCE) and cellular proliferation were studied in lymphocytes from 16 pregnant and 18 non-pregnant women. A lowered SCE frequency was found in lymphocytes obtained from pregnant women (9.41 +/- 0.39 vs. 11.07 +/- 0.42 SCE/metaphase in non-pregnant women). Lower proliferation rates were also common for cultures of pregnant women. Thus, physiological changes occurred in the organism of pregnant women may influence various cytogenetic indices registered in human peripheral blood cultures.     

Lack of effect of thyrotropin releasing hormone (TRH) in circulatory shock

Thyrotropin releasing hormone (TRH) has been reported to reverse hypotension induced by a variety of agents and thus it has been suggested to be of therapeutic value in circulatory shock. We have investigated TRH (2 mg/kg bolus plus 2 mg/kg/hr infusion) in both hemorrhagic (cats) and traumatic shock (rats). TRH induced a pressor effect of 23 +/- 8 mm Hg (p less than 0.05) in cats and 19 +/- 3 mm Hg (p less than 0.01) in rats during hypotension. However, this transient (10-15 min) response did not result in any sustained improvement in the cardiovascular status of the animals in either shock model when compared to the vehicle. In addition, TRH did not attenuate any of the biochemical indices of the severity of the shock state (i.e., plasma amino-nitrogen concentrations, or plasma cathepsin D and MDF activities) nor did it improve survival time in traumatic shock (2.8 +/- 0.4 vs. 2.0 +/- 0.2 hours). Furthermore, TRH resulted in a significant blunting of the maximum post-reinfusion superior mesenteric artery flow and enhanced beta-glucuronidase release from liver lysosomal preparations in vitro. These potentially detrimental effects in conjunction with the lack of any overt protective effect under the conditions existing in these two shock models, do not provide evidence that TRH is beneficial as a therapeutic agent in circulatory shock.