Changes in the cytogenetic indices in the bone marrow cells of white rats undergoing mechanical trauma of various degrees of severity

The influence of traumatic shock on some cytogenetic indices in bone marrow cells was investigated in white mongrel rats. The traumatic shock was caused by the Noble-Collip method. Comparative analyses of cytogenetic indices during trauma of different intensity show that the most acute changes involve the percentage of aberrant metaphases, and of average number of chromosome breaks per cell. Dynamics of changes of cytogenetic indices after a heavy trauma show that the traumatic shock may exert a cytogenetic effect maintaining for 18 hours. The results obtained and the analysis of literary data enables us to suggest that the speed of development of changes, and restoration of cytogenetic indices under various forms of trauma is quite different and may serve another confirmation of the hypothesis above the possibility of increasing the process of mutagenesis at the expense of the violation of homeostasis.     

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.     

Systemic circulatory reaction in the initial period of Cannon's traumatic shock

In experiments on dogs it was shown that on the basis of the dynamics of circulatory parameters it is possible to divide the erectile phase of traumatic shock into two periods. The first period, similar to "defence reactions" in dangerous situations and under the action of potent non-specific stimuli, is characterized by an increased blood inflow to the myocardium, rise in the cardiac output and reduction of the tonus in peripheral vessels. The second period is characterized by the beginning of decompensation of the cardiovascular system. It is completed by the development of the torpid phase of shock.     

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.     

沙漠干热环境创伤失血性休克猪模型的氧代谢特点

目的:探讨沙漠干热环境创伤失血性休克猪的氧代谢特点。方法:选择长白仔猪40头,随机分为四组:常温假手术组(NS)、常温创伤失血性休克组(NTHS)、干热假手术组(DS)、干热创伤失血性休克组(DTHS),分别置于相应的环境暴露3小时后,进行麻醉,动静脉置管,NTHS组和DTHS组分别自剖腹术后,行左下叶1/4肝脏切除及脾切除术后,再快速放血至平均动脉压(MAP)降至45±5mmHg;NS组和DS组仅行腹中线剖腹术。持续检测计算动脉、混合静脉氧饱和度、氧含量及氧输送(DO_2)、氧耗(VO_2)、氧摄取率(O_2ER)和动脉血乳酸(Lac)。结果:整个病程中,各组动脉氧饱和度均无显著变化。DTHS组混合静脉氧饱和度和氧含量均较相同时间点的其他各组低,DO_2、VO_2、O_2ER均显著高于常温环境组(P0.05)。模型成功后,NTHS组和DTHS组DO_2均经历"下降-代偿-稳定"的过程,但DTHS组短暂稳定后立即呈进行性快速下降至到动物死亡。在实验过程中,DTHS组各时间点氧摄取率(O_2ER)均高于相同时间点的其他组,差异具有统计学意义(P0.05)。NTHS组和DTHS组氧O_2ER均在休克后0 h出现明显变化,而动脉血乳酸(Lac)在休克后1.5 h才出现明显变化,但DTHS组动脉Lac增高较NTHS组升高更加明显(P0.05),且进展迅速。结论:(1)沙漠干热环境创伤失血性休克较高的氧代谢,是机体代偿能力弱、病程变化快的重要原因之一;(2)VO_2、O_2ER等直接氧代谢指标可作为早期评估监测机体氧代谢的敏感指标;(3)血Lac浓度可能是反映干热环境创伤失血性休克严重程度的重要指标。     

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.     

Inhibitors of lipoxygenase products improve survival in traumatic shock

We have used three selective inhibitors of arachidonic acid metabolism in order to investigate the role of lipoxygenase metabolites in the pathogenesis of traumatic shock (LD₉₀). The following inhibitors were used: CGS-5391B (2.5 mg/kg), a cyclooxygenase and lipoxygenase inhibitor, CGS-5677 (2.0 mg/kg), a selective lipoxygenase inhibitor, and U-60, 257 (0.3 mg/kg), a putative inhibitor of glutathione-s-transferase. These inhibitors did not alter arterial blood pressure or heart rate when given to sham shock rats. The traumatic shock model was characterized by a 4.5-fold increase in plasma cathepsin D activity, a 4-fold increase in plasma myocardial depressant factor (MDF) activity, and a mean survival time of 1.5 ± 0.2 h. Only the dual inhibitor significantly blunted the accumulation of cathepsin D in the plasma (7.5 ± 0.8 vs 11.3 ± 0.8 U/ml, p<0.01). However, all three inhibitors significantly suppressed plasma MDF accumulation by 50–60%: CGS-5391B, CGS-5677, and U-60,2257 (p<0.01). Moreover, these three agents significantly improved survival time in traumatic shock. The increased survival time and reduced MDF activity afforded by these inhibitors suggest a significant role for lipoxygenase metabolites, particularly LTC₄ and LTD₄, in the pathogenesis of traumatic shock.     

Effect of Staphylococcal Enterotoxin B on the Electroencephalogram of Monkeys

A highly purified preparation of staphylococcal enterotoxin B was administered intravenously, 1 mg/kg, to rhesus monkeys. Electroencephalograms (EEG) were recorded from electrodes attached to the skin or implanted on the dura. The dose of toxin employed consistently produced a sequence of vascular collapse followed by death; in control studies, animals were bled periodically to produce a similar pattern of shock. Regardless of the time to death following administration of the enterotoxin, there were essentially no changes from base line EEG patterns until shortly before death. With the development of preterminal severe shock, there was a marked decrease in EEG wave frequency and an initial increase in amplitude. The latter diminished progressively to produce an isoelectric tracing immediately prior to death. This could be reversed for a brief period by epinephrine. An identical sequence of EEG changes was observed during the terminal period of hemorrhagic shock. It is postulated that cerebral anoxia, caused by inadequate blood flow, is the primary cause of the altered EEG patterns that accompany enterotoxin toxicity. In this respect, staphylococcal enterotoxin B produces changes apparently similar to bacterial endotoxin but distinctly different from the EEG effects reported after botulinum toxin, anthrax toxin, or rattlesnake and cobra venom.     

Pathomorphology of stellate ganglia in thermal injuries of the body

Structural changes of stellate-ganglia in 80 patients aged from 20 to 80 dead in different stages of burn disease (shock, toxemia, septico-toxemia and burn exhaustion) were studied with neurohistological and neurohistochemical methods. It was determined that the increasing of neuron's reactivity was the sign of its changes at the early stages of burn disease. Later hypertrophy, atrophy and neuron's body destruction took place. At the period of burn shock excessively bright luminescence sympathetic neurons prevailed, at the period of toxemia its number decreased. At the period of toxemia and septico-toxemia for the first time it was determined the increase of lipofuscin insertion in adrenergic neurons as well as the increase of the activity not only at the shock period but also at the next periods of burn disease.     

Urinary metabolic network analysis in trauma, hemorrhagic shock, and resuscitation

Hemorrhagic shock, often a result of traumatic injury, is a condition of reduced perfusion that results in diminished delivery of oxygen to tissues. The disruption in oxygen delivery induced by both ischemia (diminished oxygen delivery) and reperfusion (restoration of oxygen delivery) has profound consequences for cellular metabolism and the maintenance of homeostasis. The pathophysiologic state associated with traumatic injury and hemorrhagic shock was studied with a scale-invariant metabolic network. Urinary metabolic profiles were constructed from NMR spectra of urine samples collected at set timepoints in a porcine model of hemorrhagic shock that included a pulmonary contusion, a liver crush injury, and a 35 % controlled bleed. The network was constructed from these metabolic profiles. A partial least squares discriminant analysis (PLS-DA) model that discriminates by experimental timepoint was also constructed. Comparisons of the network (functional relationships among metabolites) and PLS-DA model (observable relationships to experimental time course) revealed complementary information. First, ischemia/reperfusion injury and evidence of cell death due to hemorrhage was associated with early resuscitation timepoints. Second, evidence of increased protein catabolism and traumatic injury was associated with late resuscitation timepoints. These results are concordant with generally accepted views of the metabolic progression of shock.     

Functional state of the endogenous opioid peptide system in traumatic shock in rats]

The experiments have been performed on 120 Wistar rats and 546 CBWH mice. Met-enkephalin (ME) and beta-endorphin (BE) levels were determined to increase in blood and mid-brain 3 hours later after soft tissue compression of pelvic extremities. 48 hours later after six-hour compression BE and ME level in blood was increased, BE concentration in blood was also increased, and enkephalins' content in brain and blood was decreased as against the control. Opioid peptides influence on the host compression period has been studied. D-agonists were established to decrease, but mu-agonists were established to increase mice survival in shock. Opioid peptides' significance in traumatic shock pathogenesis is being discussed.     

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.     

Microcirculatory disorders in the connective tissue structures of certain organs in traumatic shock with acute hemorrhage]

The present work is a fragment of the author's complex study of replantation of an extremity in experiment. Experiments on reproduction of the model of traumatic shock with acute loss of blood under conditions of muscle relaxation proposed by Yu. V. Kiprenski were performed in 15 dogs and 10 cats. It was established that in animals dead as a result of shock there appeared severe disorders of microcirculation in tissues and organs. They were characterized by a pronounced spasm of the vessels of the arteriolar link and dilatation of the venular and lymph collectors of the microcirculation bed. Simultaneously a great number of arterio-venular anastomoses were opened through which the arterial blood was shunted partly to avoid constricted capillaries. In the vessels of the venular link of the microcirculatory bed there appeared aggregations of formed elements of blood and microemboles. In absence of specific complex therapy, as it was in our experiments, the animals die of shock within the period from 17 min to 5 hour 20 min.     

Effect of enkephalins on the energy potential of the rat liver and cerebral cortex during an early period of traumatic shock

The experiments were performed on 86 white male rats, weighing 180-220 g. The animals with traumatic shock revealed a decrease in ATP concentration and a rise in ADP and AMP levels in the brain cortex and hepatic tissue, resulting in the energy charge reduction. The injection of synthetic leu-enkephalin analog D-ala2-arg6-leu-enkephalin to animals with traumatic shock led to energy charge normalization in the brain cortex and increase in hepatic tissue. The mechanisms of enkephalin effect on the energy metabolism during shock are discussed.     

Expression of hsp90 mediates cytoprotective effects in the gastrodermis of planarians

Heat shock proteins (HSPs) play a crucial role in the protection of cells. In the present study, we have identified an hsp90-related gene (Djhsp90) encoding a cytosolic form of HSP90 that is primarily expressed in gastrodermis of the planarian Dugesia japonica. Djhsp90 becomes significantly induced after traumatic amputation or other stress stimuli, such as exposure to X-ray or ultraviolet radiations, heat shock, or prolonged starvation. When Djhsp90 is silenced by ribonucleic acid interference (RNAi), planarians dramatically decrease in size, becoming unable to eat, and die in a few weeks. Our results indicate that this gene plays an essential cytoprotective role in the gastrodermis of planarians and suggest that this chaperone can be involved in autophagic processes that are activated by this tissue.     

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.     

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.     

A microarray analysis of the effects of moderate hypothermia and rewarming on gene expression by human hepatocytes (HepG2)

The gene expression changes produced by moderate hypothermia are not fully known, but appear to differ in important ways from those produced by heat shock. We examined the gene expression changes produced by moderate hypothermia and tested the hypothesis that rewarming after hypothermia approximates a heat-shock response. Six sets of human HepG2 hepatocytes were subjected to moderate hypothermia (31°C for 16 h), a conventional in vitro heat shock (43°C for 30 min) or control conditions (37°C), then harvested immediately or allowed to recover for 3 h at 37°C. Expression analysis was performed with Affymetrix U133A gene chips, using analysis of variance-based techniques. Moderate hypothermia led to distinct time-dependent expression changes, as did heat shock. Hypothermia initially caused statistically significant, greater than or equal to twofold changes in expression (relative to controls) of 409 sequences (143 increased and 266 decreased), whereas heat shock affected 71 (35 increased and 36 decreased). After 3 h of recovery, 192 sequences (83 increased, 109 decreased) were affected by hypothermia and 231 (146 increased, 85 decreased) by heat shock. Expression of many heat shock proteins was decreased by hypothermia but significantly increased after rewarming. A comparison of sequences affected by thermal stress without regard to the magnitude of change revealed that the overlap between heat and cold stress was greater after 3 h of recovery than immediately following thermal stress. Thus, while some overlap occurs (particularly after rewarming), moderate hypothermia produces extensive, time-dependent gene expression changes in HepG2 cells that differ in important ways from those induced by heat 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.     

限制性液体复苏对多发性骨折合并创伤失血性休克患者凝血功能、心肌损害指标及预后的影响

目的:探讨限制性液体复苏对多发性骨折合并创伤失血性休克患者凝血功能、心肌损害指标及预后的影响。方法:选取我院收治的多发性骨折合并创伤失血性休克患者77例,分为研究组(n=39)、对照组(n=38),对照组给予常规液体复苏,研究组给予限制性液体复苏,比较两组患者凝血功能、心肌损害指标、输液量、失血量、输血量、并发症发生率及病死率。结果:研究组的输液量、失血量、输血量均少于对照组(P0.05)。与复苏前相比,两组患者复苏1 h后凝血酶原时间(PT)、凝血活酶时间(APTT)、凝血酶时间(TT)均延长,且研究组长于对照组(P0.05);两组患者复苏1 h后肌酸激酶(CK)、肌酸激酶-同工酶(CK-MB)、肌钙蛋白T(CTnT)水平均下降,且研究组低于对照组(P0.05)。研究组复苏期间并发症发生率、病死率均低于对照组(P0.05)。结论:限制性液体复苏治疗多发性骨折合并创伤失血性休克患者,可改善患者凝血功能和预后,降低并发症发生率,同时还可减轻心肌损害。