The impact of hindlimb disuse on sepsis‐induced myopathy in mice
Abstract Sepsis induces a myopathy characterized by loss of muscle mass and weakness. Septic patients undergo prolonged periods of limb muscle disuse due to bed rest. The contribution of limb muscle disuse to the myopathy phenotype remains poorly described. To characterize sepsis‐induced myopathy wi...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2021-07-01
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| Series: | Physiological Reports |
| Subjects: | |
| Online Access: | https://doi.org/10.14814/phy2.14979 |
| _version_ | 1818644983265099776 |
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| author | Orlando Laitano Jose Pindado Isela Valera Ray A. Spradlin Kevin O. Murray Katelyn R. Villani Jamal M. Alzahrani Terence E. Ryan Philip A. Efron Leonardo F. Ferreira Elisabeth R. Barton Thomas L. Clanton |
| author_facet | Orlando Laitano Jose Pindado Isela Valera Ray A. Spradlin Kevin O. Murray Katelyn R. Villani Jamal M. Alzahrani Terence E. Ryan Philip A. Efron Leonardo F. Ferreira Elisabeth R. Barton Thomas L. Clanton |
| author_sort | Orlando Laitano |
| collection | DOAJ |
| description | Abstract Sepsis induces a myopathy characterized by loss of muscle mass and weakness. Septic patients undergo prolonged periods of limb muscle disuse due to bed rest. The contribution of limb muscle disuse to the myopathy phenotype remains poorly described. To characterize sepsis‐induced myopathy with hindlimb disuse, we combined the classic sepsis model via cecal ligation and puncture (CLP) with the disuse model of hindlimb suspension (HLS) in mice. Male C57bl/6j mice underwent CLP or SHAM surgeries. Four days after surgeries, mice underwent HLS or normal ambulation (NA) for 7 days. Soleus (SOL) and extensor digitorum longus (EDL) were dissected for in vitro muscle mechanics, morphological, and histological assessments. In SOL muscles, both CLP+NA and SHAM+HLS conditions elicited ~20% reduction in specific force (p < 0.05). When combined, CLP+HLS elicited ~35% decrease in specific force (p < 0.05). Loss of maximal specific force (~8%) was evident in EDL muscles only in CLP+HLS mice (p < 0.05). CLP+HLS reduced muscle fiber cross‐sectional area (CSA) and mass in SOL (p < 0.05). In EDL muscles, CLP+HLS decreased absolute mass to a smaller extent (p < 0.05) with no changes in CSA. Immunohistochemistry revealed substantial myeloid cell infiltration (CD68+) in SOL, but not in EDL muscles, of CLP+HLS mice (p < 0.05). Combining CLP with HLS is a feasible model to study sepsis‐induced myopathy in mice. Hindlimb disuse combined with sepsis induced muscle dysfunction and immune cell infiltration in a muscle dependent manner. These findings highlight the importance of rehabilitative interventions in septic hosts to prevent muscle disuse and help attenuate the myopathy. |
| first_indexed | 2024-12-17T00:23:31Z |
| format | Article |
| id | doaj.art-358f8f58bff24df79d0a3e6ac1268257 |
| institution | Directory Open Access Journal |
| issn | 2051-817X |
| language | English |
| last_indexed | 2024-12-17T00:23:31Z |
| publishDate | 2021-07-01 |
| publisher | Wiley |
| record_format | Article |
| series | Physiological Reports |
| spelling | doaj.art-358f8f58bff24df79d0a3e6ac12682572022-12-21T22:10:31ZengWileyPhysiological Reports2051-817X2021-07-01914n/an/a10.14814/phy2.14979The impact of hindlimb disuse on sepsis‐induced myopathy in miceOrlando Laitano0Jose Pindado1Isela Valera2Ray A. Spradlin3Kevin O. Murray4Katelyn R. Villani5Jamal M. Alzahrani6Terence E. Ryan7Philip A. Efron8Leonardo F. Ferreira9Elisabeth R. Barton10Thomas L. Clanton11Department of Nutrition and Integrative Physiology College of Health and Human SciencesFlorida State University Tallahassee FL USADepartment of Nutrition and Integrative Physiology College of Health and Human SciencesFlorida State University Tallahassee FL USADepartment of Nutrition and Integrative Physiology College of Health and Human SciencesFlorida State University Tallahassee FL USADepartment of Applied Physiology and Kinesiology College of Health and Human PerformanceUniversity of Florida Gainesville FL USADepartment of Applied Physiology and Kinesiology College of Health and Human PerformanceUniversity of Florida Gainesville FL USADepartment of Applied Physiology and Kinesiology College of Health and Human PerformanceUniversity of Florida Gainesville FL USADepartment of Applied Physiology and Kinesiology College of Health and Human PerformanceUniversity of Florida Gainesville FL USADepartment of Applied Physiology and Kinesiology College of Health and Human PerformanceUniversity of Florida Gainesville FL USADepartment of Surgery College of MedicineUniversity of Florida Gainesville FL USADepartment of Applied Physiology and Kinesiology College of Health and Human PerformanceUniversity of Florida Gainesville FL USADepartment of Applied Physiology and Kinesiology College of Health and Human PerformanceUniversity of Florida Gainesville FL USADepartment of Applied Physiology and Kinesiology College of Health and Human PerformanceUniversity of Florida Gainesville FL USAAbstract Sepsis induces a myopathy characterized by loss of muscle mass and weakness. Septic patients undergo prolonged periods of limb muscle disuse due to bed rest. The contribution of limb muscle disuse to the myopathy phenotype remains poorly described. To characterize sepsis‐induced myopathy with hindlimb disuse, we combined the classic sepsis model via cecal ligation and puncture (CLP) with the disuse model of hindlimb suspension (HLS) in mice. Male C57bl/6j mice underwent CLP or SHAM surgeries. Four days after surgeries, mice underwent HLS or normal ambulation (NA) for 7 days. Soleus (SOL) and extensor digitorum longus (EDL) were dissected for in vitro muscle mechanics, morphological, and histological assessments. In SOL muscles, both CLP+NA and SHAM+HLS conditions elicited ~20% reduction in specific force (p < 0.05). When combined, CLP+HLS elicited ~35% decrease in specific force (p < 0.05). Loss of maximal specific force (~8%) was evident in EDL muscles only in CLP+HLS mice (p < 0.05). CLP+HLS reduced muscle fiber cross‐sectional area (CSA) and mass in SOL (p < 0.05). In EDL muscles, CLP+HLS decreased absolute mass to a smaller extent (p < 0.05) with no changes in CSA. Immunohistochemistry revealed substantial myeloid cell infiltration (CD68+) in SOL, but not in EDL muscles, of CLP+HLS mice (p < 0.05). Combining CLP with HLS is a feasible model to study sepsis‐induced myopathy in mice. Hindlimb disuse combined with sepsis induced muscle dysfunction and immune cell infiltration in a muscle dependent manner. These findings highlight the importance of rehabilitative interventions in septic hosts to prevent muscle disuse and help attenuate the myopathy.https://doi.org/10.14814/phy2.14979atrophyinfectioninflammationmuscleseptic shockweakness |
| spellingShingle | Orlando Laitano Jose Pindado Isela Valera Ray A. Spradlin Kevin O. Murray Katelyn R. Villani Jamal M. Alzahrani Terence E. Ryan Philip A. Efron Leonardo F. Ferreira Elisabeth R. Barton Thomas L. Clanton The impact of hindlimb disuse on sepsis‐induced myopathy in mice Physiological Reports atrophy infection inflammation muscle septic shock weakness |
| title | The impact of hindlimb disuse on sepsis‐induced myopathy in mice |
| title_full | The impact of hindlimb disuse on sepsis‐induced myopathy in mice |
| title_fullStr | The impact of hindlimb disuse on sepsis‐induced myopathy in mice |
| title_full_unstemmed | The impact of hindlimb disuse on sepsis‐induced myopathy in mice |
| title_short | The impact of hindlimb disuse on sepsis‐induced myopathy in mice |
| title_sort | impact of hindlimb disuse on sepsis induced myopathy in mice |
| topic | atrophy infection inflammation muscle septic shock weakness |
| url | https://doi.org/10.14814/phy2.14979 |
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