RIG-I, a novel DAMPs sensor for myoglobin activates NF-κB/caspase-3 signaling in CS-AKI model.

BACKGROUND: Acute kidney injury (AKI) is the main life-threatening complication of crush syndrome (CS), and myoglobin is accepted as the main pathogenic factor. The pattern recognition receptor retinoicacid-inducible gene I (RIG-I) has been reported to exert anti-viral effects function in the innate immune response. However, it is not clear whether RIG-I plays a role in CS-AKI. The present research was carried out to explore the role of RIG-I in CS-AKI. METHODS: Sprague-Dawley rats were randomly divided into two groups: the sham and CS groups (n = 12). After administration of anesthesia, the double hind limbs of rats in the CS group were put under a pressure of 3 kg for 16 h to mimic crush conditions. The rats in both groups were denied access to food and water. Rats were sacrificed at 12 h or 36 h after pressure was relieved. The successful establishment of the CS-AKI model was confirmed by serum biochemical analysis and renal histological examination. In addition, RNA sequencing was performed on rat kidney tissue to identify molecular pathways involved in CS-AKI. Furthermore, NRK-52E cells were treated with 200 µmol/L ferrous myoglobin to mimic CS-AKI at the cellular level. The cells and cell supernatant samples were collected at 6 h or 24 h. Small interfering RNAs (siRNA) was used to knock down RIG-I expression. The relative expression levels of molecules involved in the RIG-I pathway in rat kidney or cells samples were measured by quantitative Real-time PCR (qPCR), Western blotting analysis, and immunohistochemistry (IHC) staining. Tumor necrosis factor-α (TNF-α) was detected by ELISA. Co-Immunoprecipitation (Co-IP) assays were used to detect the interaction between RIG-I and myoglobin. RESULTS: RNA sequencing of CS-AKI rat kidney tissue revealed that the different expression of RIG-I signaling pathway. qPCR, Western blotting, and IHC assays showed that RIG-I, nuclear factor kappa-B (NF-κB) P65, p-P65, and the apoptotic marker caspase-3 and cleaved caspase-3 were up-regulated in the CS group (P < 0.05). However, the levels of interferon regulatory factor 3 (IRF3), p-IRF3 and the antiviral factor interferon-beta (IFN-ß) showed no significant changes between the sham and CS groups. Co-IP assays showed the interaction between RIG-I and myoglobin in the kidneys of the CS group. Depletion of RIG-I could alleviate the myoglobin induced expression of apoptosis-associated molecules via the NF-κB/caspase-3 axis. CONCLUSION: RIG-I is a novel damage-associated molecular patterns (DAMPs) sensor for myoglobin and participates in the NF-κB/caspase-3 signaling pathway in CS-AKI. In the development of CS-AKI, specific intervention in the RIG-I pathway might be a potential therapeutic strategy for CS-AKI.

Venous bicarbonate and creatine kinase as diagnostic and prognostic tools in the setting of acute traumatic rhabdomyolysis.

BACKGROUND: Myorenal or crush syndrome often develops following soft-tissue traumatic injury. It is a spectrum of disease that may result in severe renal dysfunction and kidney injury requiring renal replacement therapy. OBJECTIVES: To review a large cohort of patients with so-called myorenal or crush syndrome and assess the biochemical markers of venous bicarbonate and creatine kinase as predictors for the development of acute kidney injury (AKI). METHODS: All patients with myorenal syndrome who presented to Khayelitsha District Hospital, Cape Town, South Africa (SA), and Ngwelezana Hospital, Empangeni, KwaZulu-Natal, SA, between January and December 2017 were identified and reviewed. RESULTS: A total of 212 patients were included in the study. At both hospitals, 94% of the patients were male. Using the Pearson correlation coefficient, we compared creatinine kinase (CK) against serum creatinine. The mean CK level was 5 311.8 U/L and the mean creatinine level 133.457 µmol/L. The r-value was 0.2533. Although this is a technically positive correlation, the relationship between the variables is weak. Using the Pearson R Calculator, we inserted the r-value to calculate the p-value. The p-value was 0.000208. When comparing venous bicarbonate (HCO3) against creatinine, the mean HCO3 level was 22.296 mmol/L and the mean creatinine level 162.053 µmol/L. The r-value was -0.3468. Although this is a technically negative correlation, the relationship between the variables is weak. Using the Pearson R Calculator, we inserted the r-value to calculate the p-value. The p-value was 0.000013. The inverse ratio shown with HCO3 v. creatinine, although still a weak correlation, is significantly better in predicting an increase in creatinine compared with the weak positive correlation of CK v. creatinine. CONCLUSIONS: Although both venous HCO3 and CK showed a weak correlation with creatinine, the former performed significantly better in predicting AKI. In a resource-constrained system, we recommend that HCO3 be measured to assess patients with crush injury and that CK be regarded as a complementary modality.

Combined administration of anisodamine and neostigmine rescued acute lethal crush syndrome through α7nAChR-dependent JAK2-STAT3 signaling.

Previously we showed that Ani (anisodamine)/Neo (neostigmine) combination produced anti-shock effect via activating α7 nicotinic acetylcholine receptor (α7nAChR). In this study, we aim to investigate the therapeutic effect and underlying mechanisms of Ani/Neo combination in acute lethal crush syndrome (CS). In rat and rabbit CS models, Ani/Neo combination increased the 24 h survival rates, improved hemodynamics and decreased the levels of creatine kinase, MB isoenzyme of creatine kinase, blood urea nitrogen, creatinine, K+ in serum. It also decreased the levels of H2O2, myeloperoxidase (MPO) and nitric oxide (NO) in serum and compressed muscle in rat CS model. In wild-type (WT) mice with CS, Ani/Neo combination increased 24 h survival rate and decreased the levels of H2O2, MPO, NO, TNFα, IL-6 and IL-10 in compressed muscle. These effects were attenuated by α7nAChR knockout (KO). Moreover, Ani/Neo combination prevented the decrease of phosphorylation of Janus kinase 2 (JAK2) and phosphorylation of signal transducer and activator of transcription 3 (STAT3) induced by CS. These effects of Ani/Neo in CS mice were cancelled by methyllycaconitine (α7nAChR antagonist) and α7nAChR KO. Collectively, our results demonstrate that Ani/Neo combination could produce therapeutic effects in CS. The underlying mechanism involves the activation of α7nAChR-dependent JAK2-STAT3 signaling pathway.

CHANGES OF ENDOTHELIN-1 CONTENT AND BLOOD RHEOLOGICAL PROPERTIES IN CRUSH SYNDROME.

This study describes hematocrit values and quantitative changes in plasma endothelin-1 (ET-1) levels according to the severity of crush syndrome (CS) compression and decompression periods. The experiments were carried out on 50 randomly selected 200-250 gr mass Wistar rats with the use of the standard crush syndrome modeling method. The plasma level of ET-1 was determined by the immuneenzyme method with the use of ELISA REDEAR URIT 660. Hematocrit was determined using the standard method and measured according to tube column divisions. Our data show that ET-1 and hematocrit values rise commensurate with an increased duration of compression, and especially decompression periods. In CS, elevation of ET-1 concentrations and hematocrit values leads to significant microcirculation disturbances in parallel with longer and more severe compression and decompression periods. Specifically, the ET-1 concentration was significantly elevated, possibly in response to activation of surface endothelial В (ET-B) receptors located in the vessel endothelium. These receptors, in turn, have a vasodilative effect due to nitrogen oxide synthesis induction and vascular smooth muscle relaxation. The rise in hematocrit values during crush syndrome is associated with plasmorrhagia induced by trauma and toxic (rhabdomyolysis) shock.

Effects of acetaminophen and mannitol on crush injuries in rats: An experimental study.

BACKGROUND: The present objective was to evaluate effects of acetaminophen and mannitol on renal function and histopathology in crush injuries. METHODS: Thirty-six rats weighing 370-400 g each were used. No surgery was performed on the first (control) group. The gastrocnemius muscle regions of each rat in the remaining 5 groups were compressed for 2 or 24 hours. In the 4th group, 100 mg/kg acetaminophen was intraperitoneally administered. In the 5th group, 1 g/kg mannitol was administered. In the 6th group, 100 mg/kg acetaminophen and 1 g/kg mannitol were administered. RESULTS: No statistically significant differences were observed among the treatment groups in terms of sodium, potassium, alanine aminotransferase (ALT), and average creatinine clearance values. Hydropic degeneration, tubular necrosis, presence of immunoperoxidase and myoglobin, tubulus epithelial cell degeneration, and presence of PAS-dyed material in tubular lumen was more prominently decreased in the acetaminophen group than the mannitol group. Improvement was observed in the group that was administered both drugs, compared to the mannitol-only group, though findings were still worse than those of the group administered acetaminophen only. CONCLUSION: In crush injuries, acetaminophen improves histopathological renal damage better than mannitol. When used in conjunction with mannitol, the toxic effect of acetaminophen on the liver is decreased.

Early Therapeutic Intervention for Crush Syndrome: Characterization of Intramuscular Administration of Dexamethasone by Pharmacokinetic and Biochemical Parameters in Rats.

Crush syndrome (CS) is the systemic manifestation of muscle cell damage resulting from pressure and crushing. It is associated with a high mortality rate, even when patients are treated with conventional therapy. We demonstrated the utility of intramuscular administration of dexamethasone (DEX) in disaster medical care by using a model of CS to characterize the pharmacokinetics and biochemical parameters. We compared intravenous (IV) and intramuscular (IM) injection. The IM sites were the right anterior limb (AL), bilateral hind limbs (bHL), and unilateral hind limb (uHL). DEX (5.0 mg/kg) was administered in sham-operated (sham, S-IV, S-AL, S-bHL, S-uHL groups) and CS rats (control, C-IV, C-AL, C-bHL, C-uHL groups). The survival rate in the IM groups was lower than that in the C-IV group. Survival was highest in the C-AL group, followed by the C-uHL and C-bHL groups. The blood DEX concentration of the C-AL group was similar to that in the C-IV group. The C-bHL and C-uHL groups had decreased blood DEX concentrations. Moreover, inhibition of inflammation was related to these changes. Administration of DEX to non-injured muscle, as well as IV administration, increased the survival rate by modulating shock and inflammatory mediators, consequently suppressing myeloperoxidase activity and subsequent systemic inflammation, resulting in a complete recovery of rats from lethal CS. These results demonstrate that injection DEX into the non-injured muscle is a potentially effective early therapeutic intervention for CS that could easily be used in transport to the hospital.

The Beneficial Effects of ETS-GS, a Novel Vitamin E Derivative, on a Rat Model of Crush Injury.

Crush syndrome is a devastating condition leading to multiple organ failure. The mechanisms by which local traumatic injuries affect distant organs remain unknown. ETS-GS is a novel water-soluble, stable anti-oxidative agent composed of vitamin E derivative. Given that one of the main pathophysiological effects in crush syndrome is massive ischemia-reperfusion, reactive oxygen species (ROS) generated from the injured extremities would be systemically involved in distant organ damage. We investigated whether ETS-GS could suppress inflammatory response and improve mortality in a rat model of crush injury. Crush injury was induced by compression of bilateral hindlimbs for 6 h followed by release of compression. Seven-day survival was significantly improved by ETS-GS treatment. To estimate anti-oxidative and anti-inflammatory effects of ETS-GS, serum was collected 6 and 20 h after the injury. ETS-GS treatment significantly dampened the up-regulation of malondialdehyde and reduction of superoxide dismutase in the serum, which were induced by crush injury. Serum levels of interleukin 6 and high mobility group box 1 were significantly decreased in the ETS-GS group compared with those in the control group. Lung damage shown by hematoxylin-eosin staining at 20 h after the injury was ameliorated by the treatment. Ex vivo imaging confirmed that ETS-GS treatment reduced ROS generation in both the lung and the muscle following crush injury. The administration of ETS-GS could suppress ROS generation, systemic inflammation, and the subsequent organ damage, thus improving survival in a rat model of crush injury. These findings suggest that ETS-GS can become a novel therapeutic agent against crush injury.

Canine model of crush syndrome established by a digital crush injury device platform.

OBJECTIVE: To establish a canine model of crush syndrome (CS). METHODS: A total of 16 healthy adult female Beagle dogs were randomly divided into the control group (n=8) and the experimental group (n=8). The crush injury was created in the left hind leg of each dog in the experimental group. RESULTS: The biochemical indexes in the experimental group changed significantly compared to the values before extrusion. And they were also significantly different from the values of the control group. The glomerular capillary dilation, renal tubular epithelial cell degeneration, and renal interstitial lymphocytic infiltration were found in the kidneys. CONCLUSION: The canine CS model established by the digital crush injury device platform was successful according with the diagnosis of CS. It is good for the investigation of the CS mechanism and treatment using this model.

Improved survival rate by temperature control at compression sites in rat model of crush syndrome.

BACKGROUND: Crush syndrome (CS) has been reported in disasters, terrorist incidents, and accidents, and the clinical and pathologic picture has gradually been clarified. Few lethal and reproducible animal models of CS with use of a quantitative load are available. A new model is needed to investigate pathologic and therapeutic aspects of this injury. MATERIALS AND METHODS: Using a device built from commercially available components, both hindlimbs of anesthetized rats were respectively compressed for 6 h using 3.6-kg blocks. The effects of trunk warming alone without compressed hindlimbs (Group A), non-warming at room temperature (Group B), whole-body warming including compressed hindlimbs (Group C), or warming of compressed hindlimbs alone (Group D) during compression were examined. Survival rates were compared and hematological and histologic analyses were performed at specific time points after compression release. RESULTS: Limb or whole-body warming significantly worsened the survival of rats. We found a much lower survival rate of 0%-10% in animals, in which the hindlimbs were warmed during compression (Groups C and D) at 12 h after compression release, compared with 90%-100% in animals without warming of the hindlimbs (Groups A and B). Groups C and D showed significantly enhanced hyperkalemia at ≥4 h after compression release and all blood samples from dead cases showed hyperkalemia (>10 mEq/L). CONCLUSIONS: We developed a new lethal and reproducible rat CS model with a quantitative load. This study found that warming of compressed limbs worsened the survival rate and significantly enhanced hyperkalemia, apparently leading to cardiac arrest.

[Coagulation and fibrinolytic activity of lymph in various pathological conditions (review of own and literature data)].

The review presents information by the author and his collaborators, as well as literature data on the coagulation of lymph in blood loss, convulsive syndrome, trauma, crush syndrome, bums, injections of thrombin and heparin, an experimental thrombosis and other pathological conditions. It is shown that the coagulation of lymph in the development of pathological conditions in tissues may outpace changes observed in the blood. We present evidence that dissolution of fibrin clots in the lymph tissue if damaged, is many times faster than in the blood.

[Experimental study on establishment of a simple model of rats crush injury-crush syndrome].

OBJECTIVE: To establish a repeatable, simple, and effective model of rat crush injury and crush syndrome. METHODS: A total of 42 female Sprague Dawley rats (2-month-old, (CS) so as to lay a foundation for further study on CS. weighing 160-180 g) were divided randomly into the control group (n=6) and experimental group (n=36). The rats of the experimental group were used to establish the crush injury and CS model in both lower limbs by self-made crush injury mould. The survival rate and hematuria rate were observed after decompression. The biochemical indexes of blood were measured at 2, 4, 8, 12, 24, and 48 hours after decompression. The samples of muscle, kidney, and heart were harvested for morphological observation. There was no treatment in the control group, and the same tests were performed. RESULTS: Seven rats died and 15 rats had hematuria during compression in the experimental group. Swelling of the lower limb and muscle tissue was observed in the survival rats after reperfusion. The liver function test results showed that the levels of alanine transaminase and aspartate aminotransferase in the experimental group were significantly higher than those in the control group (P < 0.05). The renal function test results showed that blood urea nitrogen level increased significantly after 2 hours of decompression in the experimental group, showing significant difference when compared with that in the control group at 12, 24, and 48 hours after decompression (P < 0.05); the creatinine level of the experimental group was higher than that of the control group at 4, 8, 12, and 24 hours, showing significant difference at 8, 12, and 24 hours (P < 0.05). The serum K+ concentration of the experimental group was higher than that of the control group at all time, showing significant difference at the other time (P < 0.05) except at 2 hours. The creatine kinase level showed an increasing tendency in the experimental group, showing significant difference when compared with the level of the control group at 4, 8, 12, and 24 hours (P < 0.05). The histological examination of the experimental group showed that obvious edema and necrosis of the muscle were observed at different time points; glomeruli congestion and swelling, renal tubular epithelial cell degeneration, edema, necrosis, and myoglobin tube type were found in the kidneys; and myocardial structure had no obvious changes. CONCLUSION: The method of the crush injury and CS model by self-made crush injury mould is a simple and effective procedure and the experimental result is stable. It is a simple method to establish an effective model of rats crush injury and CS.

Hyponatraemia in patients with crush syndrome during the Wenchuan earthquake.

BACKGROUND: Although sodium disturbances are common in hospitalised patients, no study has specifically investigated the epidemiology of hyponatraemia in patients with crush syndrome. OBJECTIVES: To describe the incidence of hyponatraemia and assess its effect on outcome in patients with crush syndrome during the Wenchuan earthquake. METHODS: A retrospective study was conducted in 17 reference hospitals during the Wenchuan earthquake. We excluded patients younger than 15 years and those with missing sodium values within 3 days after being rescued from the ruins. RESULTS: Hyponatraemia (serum sodium concentration <135 mmol/l) was seen in 91/180 (50.6%) patients on admission. Compared with patients with normonatraemia, those with hyponatraemia were younger, had more severe traumatic injury and renal failure, underwent more fasciotomies, received more blood transfusion and renal replacement therapy. In the multivariable-adjusted model, the number of extremity injuries (OR=1.59, 95% CI 1.08 to 2.33) and serum creatinine (OR=1.30, 95% CI 1.07 to 1.59) were independently associated with the occurrence of hyponatraemia. Covariate adjusted multiple logistic regression analysis showed an independent mortality risk rising with hyponatraemia (OR=5.74, 95% CI 1.18 to 28.00). CONCLUSIONS: Hyponatraemia was common in the patients with crush syndrome during the Wenchuan earthquake and associated with poor prognosis. Water, commercial drinks and hypotonic intravenous fluids should be supplied carefully to patients with crush syndrome.

Impact of traumatic muscle crush injury as a cause of cardiomyocyte-specific injury: an experimental study.

BACKGROUND: Muscle crush injury commonly occurs after earthquakes, collapse of buildings and sjambok beatings, and it often induces crush syndrome if not treated promptly. The general manifestation of crush syndrome is the presence of myoglobinuria with acute renal failure. However, whether cardiomyocyte injury is induced after muscle crush injury has not been investigated. The aim of this study was to observe the effects of muscle crush injury on cardiomyocyte injury and its relationship to the changes of ANP and ET-1 levels after muscle crush injury in rats. METHODS: Muscle crush injury was produced in Male Sprague-Dawley rats. Forty-eight rats were divided into six groups. The changes of electrocardiogram (ECG) were recorded. The serum levels of K(+), Ca(2+), urea, creatinine (CR), creatine kinase (CK), creatine kinase-myocardial band (CK-MB) and cardiac troponin I (cTnI) were detected by automated biochemical analysis and automated chemiluminescence assay, respectively. The myocardial and plasma levels of ANP and ET-1 were investigated by radioimmunoassay. Myocardial apoptosis and caspase-3 protein expression were quantitatively analysed by TUNEL-staining and Western blotting, respectively. RESULTS: After six hours of decompression, the serum levels of K(+) and urea increased and ST-segment elevated and heart rates decreased pronouncedly over 48h, CR increased and Ca(2+) decreased considerably over 24h. The serum levels of CK-MB and cTnI increased significantly from 6h to 24h and CK increased markedly from 0h to 24h after decompression and then decreased slowly. However, after 48h of decompression, the serum levels of cTnI were still higher than those of the control group. Plasma levels of ANP and ET-1 increased and myocardial ANP and ET-1 decreased progressively over 48h, and changed significantly from 6h to 48h after decompression. The number of TUNEL-positive myocytes and caspase-3 protein expression were higher from 6h to 48h after decompression. Moreover, the levels of K(+), urea, CR, CK, CK-MB, cTnI and caspase-3 reached their highest values after 12h of decompression. There were significant correlations between the plasma ANP elevation and the myocardial ANP decline, between the plasma ANP elevation and the plasma ET-1 increase, and between the plasma ET-1 increase and the myocardial ET-1 decline. CONCLUSIONS: Cardiomyocyte injury was induced by muscle crush injury at the early stage of decompression but not at compression. The most dangerous period of cardiomyocyte injury was at the 12th hour of decompression. Cardiomyocyte injury may partly relate to the changes of ANP and ET-1.

Malnutrition and inflammation in acute kidney injury due to earthquake-related crush syndrome.

BACKGROUND: Malnutrition and inflammation are common and serious complications in patients with acute kidney injury (AKI). However, the profile of these complications in patients with AKI caused by crush syndrome (CS) remains unclear. This study describes the clinical characteristics of malnutrition and inflammation in patients with AKI and CS due to the Wenchuan earthquake. METHODS: One thousand and twelve victims and eighteen healthy adults were recruited to the study. They were divided into five groups: Group A was composed of victims without CS and AKI (904 cases); Group B was composed of patients with CS and AKI who haven't received renal replacement therapy (RRT) (57 cases); and Group C was composed of patients with CS and AKI receiving RRT (25 cases); Group D was composed of earthquake victims with AKI but without CS (26 cases); and Group E was composed of 18 healthy adult controls. The C-reactive protein (CRP), prealbumin, transferrin, interleukin-6 and TNF-alpha were measured and compared between Group E and 18 patients from Group C. RESULTS: The results indicate that participants in Group C had the highest level of serum creatinine, blood urea nitrogen and uric acid. Approximately 92% of patients with CS who had RRT were suffering from hypoalbuminemia. The interleukin-6 and CRP levels were significantly higher in patients with CS AKI receiving RRT than in the control group. Patients in Group C received the highest dosages of albumin, plasma or red blood cell transfusions. One patient in Group C died during treatment. CONCLUSIONS: Malnutrition and inflammation was common in patients with earthquake-related CS and had a negative impact on the prognosis of these subjects. The results of this study indicate that the use of RRT, intensive nutritional supplementation and transfusion alleviated the degree of malnutrition and inflammation in hemodialysis patients with crush syndrome.

Management of severe crush injury in a front-line tent ICU after 2008 Wenchuan earthquake in China: an experience with 32 cases.

INTRODUCTION: The experience on management of crush injury after a devastating earthquake is lacking, and there are even less reports on the front-line critical care of these patients. A front-line intensive care unit (ICU) was set up in a tent after the disastrous Wenchuan earthquake (May, 12, 2008, China), where 32 patients suffering from crush injury were treated from May 12 to May 26. This study summarized our experience on management of 32 crush injury patients in a front-line tent ICU. METHODS: We retrospectively analyzed the clinical data of 32 crush injury patients treated in our frontline tent ICU. Using limited equipment, we observed the arterial blood gas parameters, blood routine, alanine aminotransferase, lactate dehydrogenase, creatine kinase, creatinine, blood urea nitrogen, and urine protein of patients. We also closely watched for changes in crush injury symptoms, urine output, and the dangerous complications of crush injury. RESULTS: Eighteen of the 32 patients developed traumatic shock, 9 had acute renal failure, 6 had acute heart failure, 2 had stress ulcers and 4 had multiple organ dysfunction syndrome (MODS). The symptoms of 17 patients met the criteria of crush syndrome; hemodialysis and prompt surgical intervention were given to them when necessary. Prompt treatment in our tent ICU improved the symptoms of patients to different degrees. The limb distension and sensory dysfunction were improved and the urine output was increased or even restored to the normal level in some patients. Serological parameters were improved in most patients after admission. Five (15.63%) patients underwent amputation due to severe infection in our group. Six (18.75%) patients died, 4 due to MODS and 2 due to acute renal failure. CONCLUSIONS: Severe crushing injuries and life-threatening complications are major causes of death after major disasters like earthquakes. Prompt treatment and close monitoring of the severe complications are of great importance in saving patients' lives. Establishment of a well-equipped front-line ICU close to the epicentre of the earthquake allows for prompt on the spot rescue of critical patients with crush injury, greatly decreasing the mortality rate and complications and avoiding amputation. There should be sufficient equipment to meet the needs of more patients.

Serum enzyme profile characteristics of victims following the Wenchuan earthquake in China.

BACKGROUND: Earthquakes are major causes of morbidity and mortality. The Wenchuan region of China was devastated by a catastrophic earthquake on May 12, 2008, at 02:28 p.m. (Beijing time), registering magnitude 8.0 on the Richter scale and causing more than 69,181 deaths. As a first-line general hospital in the disaster area, Mianyang Central Hospital admitted a large number of the victims. METHODS: A total of 534 victims (246 males, 288 females) were categorized as non-crush injury patients (n=239), simple crush injury patients (n=136), and crush syndrome patients (n=69) according to their traumatic conditions. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyltransferase (GGT), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), cholinesterase (CHS), and creatine kinase (CK) levels were measured. RESULTS: ALT, AST, LDH, CHS, and CK levels showed significant differences among the three groups by one-way analysis of variance (ANOVA). Pearson correlation analysis showed that correlative changes between any two of the following: ALT, AST, GGT, ALP, LDH, and CHS were similar among three groups, with the following exceptions. The correlation coefficients of ALT-GGT, AST-GGT, and ALP-CHS changed from positive to negative values, and ALP-LDH changed from a negative value to a positive value. Receiver-operating characteristic (ROC) curve analysis showed the highest diagnostic effectiveness of 99.4% for CK, with 100% specificity [positive predictive value (PPV)=100%] and 99.4% sensitivity [negative predictive value (NPV)=99.0%] in distinguishing crush injury (including crush syndrome) from non-crush injury. AST had the best diagnostic effectiveness in distinguishing crush syndrome from crush injury; 53.8%, with 85.5% specificity (PPV=64.4%) and 77.9% sensitivity (NPV=90.7%). Multivariate logistic analysis revealed that CK was best at distinguishing crush injury (including crush syndrome) from non-crush injury (OR 409.636, 95% CI 382.96-438.17), and AST was best for distinguishing crush syndrome from crush injury (OR 50.08, 95% CI 46.84-53.55). CONCLUSIONS: Crush injury and crush syndrome are severe in victims following accidents or natural catastrophes. Serum CK, LDH, AST, ALT, GGT, and ALP activities were all helpful biochemical parameters in estimating the severity of crush injury and/or crush syndrome and preventing the development of further complications.

[Apparatus-free membrane plasmapheresis in the complex therapy of victims with crush syndrome during evacuation under the conditions of an aeromobile hospital of the Russian MChS Ministry].

The paper analyzes the results of treatment in victims with the crush syndrome under the conditions maximally close to those of emergency situations. It is concluded that plasma exchange procedures should be performed within the next few hours after taking the victims from the obstructions, which reduces the risk of acute lung damage and death rates in this group of patients to a considerable extent.

[Crush syndrome in severe trauma]. / Crush-sindrom (CS) u okviru teske traume.

Crush injury or traumatic rhabdomyolysis is caused by crushing of large muscule mass, usually of the femoral and gluteal compartment. Crush syndrome is general manifestation of crush injury with renal failure (ARF). ARF is caused by deposition of myoglobin in distal tubules. The concentration of serum creatin phosphokinase is an indicator of the extent of injured muscule. The serum concentration of myoglobin is an indicator of the extent of injured muscule and the main cause of development of crush syndrome. In a prospective study the concentration of myoglobin and CPK was measured in 81 patients with injuries of lower extremities and pelvis as a part of severe trauma. The increase of CPK concentration above 1000 U/L was measured in all patients. The increase of CPK concentration above 2000 U/L was measured in 78 (96.3%) patients. The increase of myoglobin concentration of >700 mcg/L was measured in 19 (23.5%) patients. In the group of 19 patients with CPK concentration of >2000 U/L and myoglobin concentration of >700 mcg/L crush syndrome developed in 6 (7.4%) patients with oliguria (urin output <50 ml/h) and the increase of serum potassium, phosphate and creatinine concentrations. The decrease of CPK and myoglobin concentrations was achieved in 5 patients during 10-12 days and 1 patient with associated craniocrebral injury died.

[The role of blood rheology and micro hemocirculation in development of generalized hypoxia in crush syndrome].

Crush syndrome (CS) is a type of traumatic pathology accompanied by intoxication of organism with a heavy and specific clinical course and high lethality. Numerous damages, the most significant of which are stress, shock, pain, violation of the neurohumoral system involving the mediators of the sympathic part of vegetative nervous system, and pathological condition in which the body as a whole (generalized hypoxia) or region of the body (tissue hypoxia) is deprived of adequate oxygen supply are common in CS. The aim of the research was to study factors, which determine tissue blood and oxygen supply and to detect the possible pathogenetic mechanisms of generalized hypoxia in decompressed tissues and organs in long CS. Systemic arterial pressure, blood supply of skeletal muscles and liver, mesenteric microcirculation, mechanical and chemical resistance of erythrocytes of rats in crash syndrome has been investigated with the use of electrotensometry, H+-clearance, telebiomicroscopy, ultrasound cytolysogram and photoelectrocolorimetry. The model of crush was created by compression of experimental animals' hip during 6 hours. The morphological study of brain tissue during different types of decompression has revealed a contraction of the vessels of the cerebral shell, hypoxia, and perivascular edema. It was stated that interrelated changes play significant role in development of generalized hypoxia of tissues; degree of disorders depend on duration of compression and decompression, reactivity of micro blood vessels; the fall of local hemocirculation in intact tissues and reduced resistance and deformability of erythrocytes takes place.

New experimental model of crush injury of the hindlimbs in rats.

BACKGROUND: Crush injury (CI) remains a life-threatening condition. Because there is a shortage of animal models of CI, we purposed to develop a reproducible model of CI of hindlimbs in rats and to evaluate correlation between the volume of muscles traumatized and the severity of CI. METHODS: The right or both hindlimbs of anesthetized rats were compressed for 6 hours under blocks weighing 3 kg. This was followed by 3 hours of reperfusion. Serum lactate, base excess (BE), and potassium (K) were measured at 10 minutes after cannulaton (baseline), immediately before release (compression), and 3 hours after release (reperfusion). Serum creatine phosphokinase (CK), lactate dehydrogenase (LDH), aspartate transferase (AST) and alanine transferase (ALT) were measured at baseline and reperfusion. Muscles and kidneys were evaluated morphologically. In a separate group of animals treated in the same way, survival rate was monitored for 168 hours. RESULTS: Unilateral CI did not induce serious systemic impairment. Bilateral CI resulted in severe lactic acidosis. Serum K levels increased similarly and significantly in both groups. Serum CK levels correlated strongly with the volume of muscles traumatized. Bilateral CI produced a sharp increase in serum LDH, AST and ALT levels by the end of experiment. Signs of direct cellular damage and ischemia-reperfusion injury were found in histology specimens. In bilaterally crushed rats there were patent signs of acute tubular necrosis at 24 hours after insult. All rats with unilateral CI survived, whereas mortality rate reached 58.3% in rats with bilateral CI. The majority of these animals died within 24 hours after compression. CONCLUSIONS: We developed a valid experimental model of severe CI of the hindlimbs in rats. Systemic responses to CI and the severity of CI appeared to correlate strongly with the volume of muscle traumatized.