Characterization of Systemic and Histologic Injury After Crush Syndrome and Intervals of Reperfusion in a Small Animal Model

Murata, Ikuo; Ooi, Kazuya; Sasaki, Hiromi; Kimura, Soichiro; Ohtake, Kazuo; Ueda, Hideo; Uchida, Hajime; Yasui, Norikiyo; Tsutsui, Yasuhiro; Yoshizawa, Naoya; Hirotsu, Ichiro; Morimoto, Yasunori; Kobayashi, Jun

doi:10.1097/ta.0b013e31820ca00a

Cited by 36 publications

(72 citation statements)

References 24 publications

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“…15) In brief, a rubber tourniquet 2.4 cm in width and 1 mm in thickness was wrapped five times around a metal cylinder (22 mm outer diameter, 20 mm internal diameter, 70 mm in length) under a 2 kg load, and the end of the band was glued.…”

Section: Animal Modelmentioning

confidence: 99%

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

Murata

Goto

Komiya

et al. 2016

Biological & Pharmaceutical Bulletin

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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. Key words crush syndrome; dexamethasone; intramuscular injection; disaster medical careCrush syndrome (CS) is often reported as a traumatic disorder with high mortality and occurs after sudden catastrophes, such as the Hanshin-Awaji, Marmara, and Wenchan earthquakes.1-3) CS is defined as the systemic manifestation of muscle cell damage resulting from pressure and crushing. 4)The typical clinical and pathological features of CS result predominantly from traumatic rhabdomyolysis and subsequent release of muscle cell contents upon rescue.5-7) Systemic manifestations may include bleeding, hypovolemic shock, cardiac failure, arrhythmia, electrolyte disturbance, psychological trauma, acute kidney injury (AKI), sepsis, systemic inflammatory response syndrome (SIRS), acute respiratory distress syndrome (ARDS), multiple organ dysfunction syndrome (MODS), and disseminated intravascular coagulation (DIC). 8)After major earthquakes, up to 20% of deaths occur shortly after extrication. 9) Some of these deaths include victims who were relatively stable before extrication, but deteriorated suddenly thereafter, and this phenomenon is called rescue death. Consequently, for affected victims and patients, it is necessary to identify who should receive an intensive care strategy. Most victims survive upon volume replacement or massive fluid resuscitation at the disaster site. However, this treatment improves symptoms of the acute phase (e.g., hyperkalemia, hypovolemic shock...

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Section: Animal Modelmentioning

confidence: 99%

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

Murata

Goto

Komiya

et al. 2016

Biological & Pharmaceutical Bulletin

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“…A simple rubber tourniquet on the hind limb can create crush injury, 20 but the pressure is difficult to be controlled accurately. Hind limb can be pressed by heavy blocks to create crush injury, 21 but the injury is not homogeneous.…”

Section: Discussionmentioning

confidence: 99%

Application of contrast-enhanced ultrasonography in the diagnosis of skeletal muscle crush injury in rabbits

Fq²,

Qy³

et al. 2014

BJR

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Objective: To explore the diagnostic value of quantitative contrast-enhanced (CE) ultrasonography for crush injury in the hind limb muscles of rabbits. Methods: A total of 120 New Zealand white rabbits were randomized to receive compression on the left hind limb for either 2 h (n 5 56) or 4 h (n 5 56) to induce muscle crush injury. Another eight animals were not injured and served as normal controls. CE ultrasonography parameters such as peak intensity (PI), ascending slop, descending slop and area under curve (AUC) were measured at 0.5, 2, 6 and 24 h and 3, 7 and 14 days after decompression. Results: Compared with the uninjured muscles, reperfusion of the injured muscles showed early and high enhancement in CE ultrasonography images. The time-intensity curve showed a trend of rapid lift and gradual drop. The PI and AUC values differed significantly among the three groups and were positively correlated with serum and tissue biomarkers. Rabbits of the 4-h compression group showed significantly higher PI and AUC values, and serum and tissue parameters than the 2-h compression group at each time points. Conclusion: CE ultrasonography can effectively detect muscle crush injury and monitor dynamic changes of the injured muscles in rabbits. PI and AUC are promising diagnostic parameters for this disease. Advances in knowledge: CE ultrasonography might play an important role in the pre-hospital and bedside settings for the diagnosis of muscle crush injury.

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“…In addition, infection and multiple system organ dysfunction (MOD) were the significant risk factors associated with earthquake-related inpatient death. Vascular endothelial injury is involved in MOD after crush injury and amplifies the inflammatory response in vivo [3].…”

Section: Introductionmentioning

confidence: 99%

Comparison of two fluid solutions for resuscitation in a rabbit model of crush syndrome

et al. 2015

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Characterization of Systemic and Histologic Injury After Crush Syndrome and Intervals of Reperfusion in a Small Animal Model

Cited by 36 publications

References 24 publications

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

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

Application of contrast-enhanced ultrasonography in the diagnosis of skeletal muscle crush injury in rabbits

Comparison of two fluid solutions for resuscitation in a rabbit model of crush syndrome

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