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Optimization of a Rhabdomyolysis Model in Mice With Exertional Heat Stroke Mouse Model of EHS-Rhabdomyolysis.

ABSTRACT: Exertional heat stroke (EHS) is a life-threatening disease characterized by high mortality and incidence of rhabdomyolysis (RM). It would therefore be valuable to establish a stable EHS-induced RM model that accurately reflects the clinical characteristics of EHS patients and provides an objective animal model for further study of the pathogenesis of RM. In the current study, 8?9-week-old, male, wild-type C57BL/6J mice, at the stage of sexual maturity, were randomly divided into four groups: the EHS group, the classical heat stroke (CHS) group, the sham heat exercise group, and sham heat rest group. The survival rate of mice was determined under relatively high levels of temperature and humidity (37.5°C, 65% relative humidity (RH); 37.5°C, 70% RH; 39.5°C, 65% RH; and 39.5°C, 70% RH) as well as a high core temperature (Tc; 42, 42.5, and 43°C). Results showed that the environmental condition of 39.5°C and 65% RH was most suitable for EHS modeling. The end point of EHS evaluation was exhaustion or an individual's core temperature reaching 43°C. The survival rate of mice in the EHS group within 24 h under these conditions was 37.34%, which is consistent with the high mortality characteristics noted in EHS patients. Severe RM was observed in the EHS group by H&E staining and transmission electron microscopy. Creatine kinase levels in the EHS group mostly exceeded 10,000 U/L, which was approximately 10 times higher than that in the sham heat rest group. Renal tubules of the EHS group exhibited severe necrosis, and calcium overload in the skeletal muscles of this group was also observed using intravital 2-photon microscopy. In conclusion, we made improvements to a stable EHS-induced RM animal model to truly reflect the clinical characteristics of EHS patients. This new model should be helpful in the further study of RM pathogenesis.

SUBMITTER: He SX

PROVIDER: S-EPMC7325941 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Optimization of a Rhabdomyolysis Model in Mice With Exertional Heat Stroke Mouse Model of EHS-Rhabdomyolysis.

He Si-Xiao SX Li Ru R Yang Huo-Hong HH Wang Zi-Qing ZQ Peng Yan-Mei YM Huang Jun-Hao JH Ma Qiang Q

Frontiers in physiology 20200616

Exertional heat stroke (EHS) is a life-threatening disease characterized by high mortality and incidence of rhabdomyolysis (RM). It would therefore be valuable to establish a stable EHS-induced RM model that accurately reflects the clinical characteristics of EHS patients and provides an objective animal model for further study of the pathogenesis of RM. In the current study, 8∼9-week-old, male, wild-type C57BL/6J mice, at the stage of sexual maturity, were randomly divided into four groups: the ...[more]

PMID: 32655408

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Project description:Reasons for performing studyAlthough exertional rhabdomyolysis (ER) is common in Arabian horses, there are no dedicated studies describing histopathological characteristics of muscle from Arabian horses with ER.ObjectivesTo prospectively identify distinctive histopathological features of muscle from Arabian endurance horses with a history of ER (pro-ER) and to retrospectively determine their prevalence in archived samples from Arabian horses with exertional myopathies (retro-ER).Study designProspective and retrospective histopathological description.MethodsMiddle gluteal muscle biopsies obtained from Arabian controls (n = 14), pro-ER (n = 13) as well as archived retro-ER (n = 25) muscle samples previously classified with type 2 polysaccharide storage myopathy (15/25), recurrent exertional rhabdomyolysis (7/25) and no pathology (3/25) were scored for histopathology and immunohistochemical staining of cytoskeletal proteins. Glutaraldehyde-fixed samples (2 pro-ER, one control) were processed for electron microscopy. Pro-ER and retro-ER groups were compared with controls using Mann-Whitney U and Fisher's exact tests.ResultsCentrally located myonuclei in mature myofibres were found in significantly more (P<0.05) pro-ER (12/13) and retro-ER (21/25) horses than controls (4/14). Degenerating myofibres were not evident in any biopsies. Retro-ER horses had amylase-resistant polysaccharide (6/25, P<0.05) and higher scores for cytoplasmic glycogen, rimmed vacuoles and rod-like bodies. A few control horses (3/14) and significantly (P<0.05) more pro-ER (12/13) and retro-ER (18/25) horses had disrupted myofibrillar alignment and large desmin and αβ-crystallin positive cytoplasmic aggregates. Prominent Z-disc degeneration and focal myofibrillar disruption with regional accumulation of β-glycogen particles were identified on electron microscopy of the 2 pro-ER samples.ConclusionsIn a subset of Arabian horses with intermittent episodes of exertional rhabdomyolysis, ectopic accumulation of cytoskeletal proteins and Z-disc degeneration bear a strong resemblance to a myofibrillar myopathy. While many of these horses were previously diagnosed with type 2 polysaccharide storage myopathy, pools of glycogen forming within disrupted myofibrils appeared to give the false appearance of a glycogen storage disorder.

Dataset Information

Optimization of a Rhabdomyolysis Model in Mice With Exertional Heat Stroke Mouse Model of EHS-Rhabdomyolysis.

Publications

Optimization of a Rhabdomyolysis Model in Mice With Exertional Heat Stroke Mouse Model of EHS-Rhabdomyolysis.

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