Taurine administration ablates sepsis induced diaphragm weakness
•Diaphragm weakness is a major clinical problem in critically ill mechanically ventilated patients.•Sepsis is a major risk factor for the development of diaphragm weakness.•Taurine administration improves sepsis-induced diaphragm dysfunction.•Taurine treatment may improve diaphragm strength and redu...
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| Veröffentlicht in: | Respiratory physiology & neurobiology 2020-01, Vol.271, p.103289-103289, Article 103289 |
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| creator | Supinski, Gerald S. Wang, Lin Schroder, Elizabeth A. Callahan, Leigh Ann P. |
| description | •Diaphragm weakness is a major clinical problem in critically ill mechanically ventilated patients.•Sepsis is a major risk factor for the development of diaphragm weakness.•Taurine administration improves sepsis-induced diaphragm dysfunction.•Taurine treatment may improve diaphragm strength and reduce duration of mechanical ventilation in critically ill patients.
Infection induced diaphragm weakness is a major contributor to death and prolonged mechanical ventilation in critically ill patients. Infection induced muscle dysfunction is associated with activation of muscle proteolytic enzymes, and taurine is known to suppress proteolysis. We therefore postulated that taurine administration may prevent infection induced diaphragm dysfunction. The purpose of this study was to test this hypothesis using a clinically relevant animal model of infection, i.e. cecal ligation puncture induced sepsis (CLP). Studies were performed on (n = 5–7 mice/group): (a) sham operated controls, (b) animals with sepsis induced by CLP, (c) sham operated animals given taurine (75 mg/kg/d, intraperitoneally), and (d) CLP animals given taurine. At intervals after surgery animals were euthanized, diaphragm force generation measured in vitro, and diaphragm calpain, caspase and proteasomal activity determined. CLP elicited a large reduction in diaphragm specific force generation at 24 h (1–150 Hz, p |
| doi_str_mv | 10.1016/j.resp.2019.103289 |
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Infection induced diaphragm weakness is a major contributor to death and prolonged mechanical ventilation in critically ill patients. Infection induced muscle dysfunction is associated with activation of muscle proteolytic enzymes, and taurine is known to suppress proteolysis. We therefore postulated that taurine administration may prevent infection induced diaphragm dysfunction. The purpose of this study was to test this hypothesis using a clinically relevant animal model of infection, i.e. cecal ligation puncture induced sepsis (CLP). Studies were performed on (n = 5–7 mice/group): (a) sham operated controls, (b) animals with sepsis induced by CLP, (c) sham operated animals given taurine (75 mg/kg/d, intraperitoneally), and (d) CLP animals given taurine. At intervals after surgery animals were euthanized, diaphragm force generation measured in vitro, and diaphragm calpain, caspase and proteasomal activity determined. CLP elicited a large reduction in diaphragm specific force generation at 24 h (1–150 Hz, p < 0.001) and taurine significantly attenuated CLP induced diaphragm weakness at all stimulation frequencies (p < 0.001). CLP induced significant increases in diaphragm calpain, caspase and proteasomal activity; taurine administration prevented increases in the activity of all three pathways. In additional time course experiments, diaphragm force generation remained at control levels over 72 h in CLP animals treated with daily taurine administration, while CLP animals demonstrated severe, sustained reductions in diaphragm strength (p < 0.01 for all time points). Our results indicate that taurine administration prevents infection induced diaphragm weakness and reduces activation of three major proteolytic pathways. Because this agent is has been shown to be safe, non-toxic when administered to humans, taurine may have a role in treating infection induced diaphragm weakness. Future clinical studies will be needed to assess this possibility.</description><identifier>ISSN: 1569-9048</identifier><identifier>EISSN: 1878-1519</identifier><identifier>DOI: 10.1016/j.resp.2019.103289</identifier><identifier>PMID: 31505275</identifier><language>eng</language><publisher>AMSTERDAM: Elsevier B.V</publisher><subject>Animals ; Diaphragm - drug effects ; Diaphragm - metabolism ; Diaphragm force generation ; Diaphragm weakness ; Life Sciences & Biomedicine ; Mice ; Muscle Weakness - drug therapy ; Muscle Weakness - etiology ; Muscle Weakness - metabolism ; Oxidative Stress - drug effects ; Oxidative Stress - physiology ; Physiology ; Proteolysis ; Respiratory System ; Science & Technology ; Sepsis ; Sepsis - complications ; Sepsis - drug therapy ; Sepsis - metabolism ; Taurine ; Taurine - pharmacology ; Taurine - therapeutic use</subject><ispartof>Respiratory physiology & neurobiology, 2020-01, Vol.271, p.103289-103289, Article 103289</ispartof><rights>2019 Elsevier B.V.</rights><rights>Copyright © 2019 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>true</woscitedreferencessubscribed><woscitedreferencescount>4</woscitedreferencescount><woscitedreferencesoriginalsourcerecordid>wos000500384200005</woscitedreferencesoriginalsourcerecordid><citedby>FETCH-LOGICAL-c455t-e2bfbd979f6c2e42ead8be0348073a8674778c0aeffa5af1e4aacfc0aa95ef493</citedby><cites>FETCH-LOGICAL-c455t-e2bfbd979f6c2e42ead8be0348073a8674778c0aeffa5af1e4aacfc0aa95ef493</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.resp.2019.103289$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,315,781,785,886,3551,27929,27930,28253,46000</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31505275$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Supinski, Gerald S.</creatorcontrib><creatorcontrib>Wang, Lin</creatorcontrib><creatorcontrib>Schroder, Elizabeth A.</creatorcontrib><creatorcontrib>Callahan, Leigh Ann P.</creatorcontrib><title>Taurine administration ablates sepsis induced diaphragm weakness</title><title>Respiratory physiology & neurobiology</title><addtitle>RESP PHYSIOL NEUROBI</addtitle><addtitle>Respir Physiol Neurobiol</addtitle><description>•Diaphragm weakness is a major clinical problem in critically ill mechanically ventilated patients.•Sepsis is a major risk factor for the development of diaphragm weakness.•Taurine administration improves sepsis-induced diaphragm dysfunction.•Taurine treatment may improve diaphragm strength and reduce duration of mechanical ventilation in critically ill patients.
Infection induced diaphragm weakness is a major contributor to death and prolonged mechanical ventilation in critically ill patients. Infection induced muscle dysfunction is associated with activation of muscle proteolytic enzymes, and taurine is known to suppress proteolysis. We therefore postulated that taurine administration may prevent infection induced diaphragm dysfunction. The purpose of this study was to test this hypothesis using a clinically relevant animal model of infection, i.e. cecal ligation puncture induced sepsis (CLP). Studies were performed on (n = 5–7 mice/group): (a) sham operated controls, (b) animals with sepsis induced by CLP, (c) sham operated animals given taurine (75 mg/kg/d, intraperitoneally), and (d) CLP animals given taurine. At intervals after surgery animals were euthanized, diaphragm force generation measured in vitro, and diaphragm calpain, caspase and proteasomal activity determined. CLP elicited a large reduction in diaphragm specific force generation at 24 h (1–150 Hz, p < 0.001) and taurine significantly attenuated CLP induced diaphragm weakness at all stimulation frequencies (p < 0.001). CLP induced significant increases in diaphragm calpain, caspase and proteasomal activity; taurine administration prevented increases in the activity of all three pathways. In additional time course experiments, diaphragm force generation remained at control levels over 72 h in CLP animals treated with daily taurine administration, while CLP animals demonstrated severe, sustained reductions in diaphragm strength (p < 0.01 for all time points). Our results indicate that taurine administration prevents infection induced diaphragm weakness and reduces activation of three major proteolytic pathways. Because this agent is has been shown to be safe, non-toxic when administered to humans, taurine may have a role in treating infection induced diaphragm weakness. Future clinical studies will be needed to assess this possibility.</description><subject>Animals</subject><subject>Diaphragm - drug effects</subject><subject>Diaphragm - metabolism</subject><subject>Diaphragm force generation</subject><subject>Diaphragm weakness</subject><subject>Life Sciences & Biomedicine</subject><subject>Mice</subject><subject>Muscle Weakness - drug therapy</subject><subject>Muscle Weakness - etiology</subject><subject>Muscle Weakness - metabolism</subject><subject>Oxidative Stress - drug effects</subject><subject>Oxidative Stress - physiology</subject><subject>Physiology</subject><subject>Proteolysis</subject><subject>Respiratory System</subject><subject>Science & Technology</subject><subject>Sepsis</subject><subject>Sepsis - complications</subject><subject>Sepsis - drug therapy</subject><subject>Sepsis - metabolism</subject><subject>Taurine</subject><subject>Taurine - pharmacology</subject><subject>Taurine - therapeutic use</subject><issn>1569-9048</issn><issn>1878-1519</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>AOWDO</sourceid><sourceid>EIF</sourceid><recordid>eNqNkU1v3CAQhlHVKt9_IIfK98pbwMaAFFWNVk0bKVIvyRmNYUjY7GILvIn678vW6aq5VDkxGt5ngAdCzhldMMq6z6tFwjwuOGW6NBqu9DtyxJRUNRNMvy-16HStaasOyXHOK0qZZLI5IIcNE1RwKY7I11vYphCxArcJMeQpwRSGWEG_hglzlXHMIVchuq1FV7kA40OC-031jPAYMedT8sHDOuPZy3pC7q6-3S5_1Dc_v18vL29q2wox1ch73zstte8sx5YjONUjbVpFZQOqk62UylJA70GAZ9gCWF8aoAX6Vjcn5Ms8d9z2G3QWY7nq2owpbCD9MgME83onhgdzPzyZTslGc1UG8HmATUPOCf2eZdTsfJqV2fk0O59m9lmgj_-eukf-CiyBT3PgGfvBZxswWtzHKKWC0ka1nO7KklZvTy_D9OcvlsM2TgW9mFEskp8CJvOCu5DQTsYN4X8P-Q0iLqs4</recordid><startdate>20200101</startdate><enddate>20200101</enddate><creator>Supinski, Gerald S.</creator><creator>Wang, Lin</creator><creator>Schroder, Elizabeth A.</creator><creator>Callahan, Leigh Ann P.</creator><general>Elsevier B.V</general><general>Elsevier</general><scope>AOWDO</scope><scope>BLEPL</scope><scope>DTL</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>5PM</scope></search><sort><creationdate>20200101</creationdate><title>Taurine administration ablates sepsis induced diaphragm weakness</title><author>Supinski, Gerald S. ; Wang, Lin ; Schroder, Elizabeth A. ; Callahan, Leigh Ann P.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c455t-e2bfbd979f6c2e42ead8be0348073a8674778c0aeffa5af1e4aacfc0aa95ef493</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Animals</topic><topic>Diaphragm - drug effects</topic><topic>Diaphragm - metabolism</topic><topic>Diaphragm force generation</topic><topic>Diaphragm weakness</topic><topic>Life Sciences & Biomedicine</topic><topic>Mice</topic><topic>Muscle Weakness - drug therapy</topic><topic>Muscle Weakness - etiology</topic><topic>Muscle Weakness - metabolism</topic><topic>Oxidative Stress - drug effects</topic><topic>Oxidative Stress - physiology</topic><topic>Physiology</topic><topic>Proteolysis</topic><topic>Respiratory System</topic><topic>Science & Technology</topic><topic>Sepsis</topic><topic>Sepsis - complications</topic><topic>Sepsis - drug therapy</topic><topic>Sepsis - metabolism</topic><topic>Taurine</topic><topic>Taurine - pharmacology</topic><topic>Taurine - therapeutic use</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Supinski, Gerald S.</creatorcontrib><creatorcontrib>Wang, Lin</creatorcontrib><creatorcontrib>Schroder, Elizabeth A.</creatorcontrib><creatorcontrib>Callahan, Leigh Ann P.</creatorcontrib><collection>Web of Science - Science Citation Index Expanded - 2020</collection><collection>Web of Science Core Collection</collection><collection>Science Citation Index Expanded</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Respiratory physiology & neurobiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Supinski, Gerald S.</au><au>Wang, Lin</au><au>Schroder, Elizabeth A.</au><au>Callahan, Leigh Ann P.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Taurine administration ablates sepsis induced diaphragm weakness</atitle><jtitle>Respiratory physiology & neurobiology</jtitle><stitle>RESP PHYSIOL NEUROBI</stitle><addtitle>Respir Physiol Neurobiol</addtitle><date>2020-01-01</date><risdate>2020</risdate><volume>271</volume><spage>103289</spage><epage>103289</epage><pages>103289-103289</pages><artnum>103289</artnum><issn>1569-9048</issn><eissn>1878-1519</eissn><abstract>•Diaphragm weakness is a major clinical problem in critically ill mechanically ventilated patients.•Sepsis is a major risk factor for the development of diaphragm weakness.•Taurine administration improves sepsis-induced diaphragm dysfunction.•Taurine treatment may improve diaphragm strength and reduce duration of mechanical ventilation in critically ill patients.
Infection induced diaphragm weakness is a major contributor to death and prolonged mechanical ventilation in critically ill patients. Infection induced muscle dysfunction is associated with activation of muscle proteolytic enzymes, and taurine is known to suppress proteolysis. We therefore postulated that taurine administration may prevent infection induced diaphragm dysfunction. The purpose of this study was to test this hypothesis using a clinically relevant animal model of infection, i.e. cecal ligation puncture induced sepsis (CLP). Studies were performed on (n = 5–7 mice/group): (a) sham operated controls, (b) animals with sepsis induced by CLP, (c) sham operated animals given taurine (75 mg/kg/d, intraperitoneally), and (d) CLP animals given taurine. At intervals after surgery animals were euthanized, diaphragm force generation measured in vitro, and diaphragm calpain, caspase and proteasomal activity determined. CLP elicited a large reduction in diaphragm specific force generation at 24 h (1–150 Hz, p < 0.001) and taurine significantly attenuated CLP induced diaphragm weakness at all stimulation frequencies (p < 0.001). CLP induced significant increases in diaphragm calpain, caspase and proteasomal activity; taurine administration prevented increases in the activity of all three pathways. In additional time course experiments, diaphragm force generation remained at control levels over 72 h in CLP animals treated with daily taurine administration, while CLP animals demonstrated severe, sustained reductions in diaphragm strength (p < 0.01 for all time points). Our results indicate that taurine administration prevents infection induced diaphragm weakness and reduces activation of three major proteolytic pathways. Because this agent is has been shown to be safe, non-toxic when administered to humans, taurine may have a role in treating infection induced diaphragm weakness. Future clinical studies will be needed to assess this possibility.</abstract><cop>AMSTERDAM</cop><pub>Elsevier B.V</pub><pmid>31505275</pmid><doi>10.1016/j.resp.2019.103289</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Diaphragm - drug effects Diaphragm - metabolism Diaphragm force generation Diaphragm weakness Life Sciences & Biomedicine Mice Muscle Weakness - drug therapy Muscle Weakness - etiology Muscle Weakness - metabolism Oxidative Stress - drug effects Oxidative Stress - physiology Physiology Proteolysis Respiratory System Science & Technology Sepsis Sepsis - complications Sepsis - drug therapy Sepsis - metabolism Taurine Taurine - pharmacology Taurine - therapeutic use |
| title | Taurine administration ablates sepsis induced diaphragm weakness |
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