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dc.contributor.authorDillon, J P
dc.contributor.authorLaing, A J
dc.contributor.authorCahill, R A
dc.contributor.authorO'Brien, G C
dc.contributor.authorStreet, J T
dc.contributor.authorWang, J H
dc.contributor.authorMc Guinness, A
dc.contributor.authorRedmond, H P
dc.date.accessioned2012-02-03T15:06:55Z
dc.date.available2012-02-03T15:06:55Z
dc.date.issued2012-02-03T15:06:55Z
dc.identifier.citationJ Orthop Res. 2005 Nov;23(6):1454-9. Epub 2005 Jul 1.en_GB
dc.identifier.issn0736-0266 (Print)en_GB
dc.identifier.issn0736-0266 (Linking)en_GB
dc.identifier.pmid15994053en_GB
dc.identifier.doi10.1016/j.orthres.2005.04.009.1100230631en_GB
dc.identifier.urihttp://hdl.handle.net/10147/208902
dc.description.abstractActivated protein C (APC) is an endogenous anti-coagulant with anti-inflammatory properties. The purpose of the present study was to evaluate the effects of activated protein C in the setting of skeletal muscle ischaemia reperfusion injury (IRI). IRI was induced in rats by applying rubber bands above the levels of the greater trochanters bilaterally for a period of 2h followed by 12h reperfusion. Treatment groups received either equal volumes of normal saline or activated protein C prior to tourniquet release. Following 12h reperfusion, muscle function was assessed electrophysiologically by electrical field stimulation. The animals were then sacrificed and skeletal muscle harvested for evaluation. Activated protein C significantly attenuated skeletal muscle reperfusion injury as shown by reduced myeloperoxidase content, wet to dry ratio and electrical properties of skeletal muscle. Further in vitro work was carried out on neutrophils isolated from healthy volunteers to determine the direct effect of APC on neutrophil function. The effects of APC on TNF-alpha stimulated neutrophils were examined by measuring CD18 expression as well as reactive oxygen species generation. The in vitro work demonstrated a reduction in CD18 expression and reactive oxygen species generation. We conclude that activated protein C may have a protective role in the setting of skeletal muscle ischaemia reperfusion injury and that this is in part mediated by a direct inhibitory effect on neutrophil activation.
dc.language.isoengen_GB
dc.subject.meshAcute Diseaseen_GB
dc.subject.meshAnimalsen_GB
dc.subject.meshAntigens, CD18/analysisen_GB
dc.subject.meshHumansen_GB
dc.subject.meshMaleen_GB
dc.subject.meshMuscle, Skeletal/*blood supplyen_GB
dc.subject.meshNeutrophil Infiltration/drug effectsen_GB
dc.subject.meshNeutrophils/drug effects/metabolismen_GB
dc.subject.meshProtein C/*therapeutic useen_GB
dc.subject.meshRatsen_GB
dc.subject.meshRats, Sprague-Dawleyen_GB
dc.subject.meshReactive Oxygen Species/metabolismen_GB
dc.subject.meshReperfusion Injury/*prevention & controlen_GB
dc.subject.meshTumor Necrosis Factor-alpha/pharmacologyen_GB
dc.titleActivated protein C attenuates acute ischaemia reperfusion injury in skeletal muscle.en_GB
dc.contributor.departmentDepartment of Academic Surgery and Orthopaedics, Cork University Hospital and, National University of Ireland, Cork, Ireland. dillionjp@o2.ieen_GB
dc.identifier.journalJournal of orthopaedic research : official publication of the Orthopaedic, Research Societyen_GB
dc.description.provinceMunster
html.description.abstractActivated protein C (APC) is an endogenous anti-coagulant with anti-inflammatory properties. The purpose of the present study was to evaluate the effects of activated protein C in the setting of skeletal muscle ischaemia reperfusion injury (IRI). IRI was induced in rats by applying rubber bands above the levels of the greater trochanters bilaterally for a period of 2h followed by 12h reperfusion. Treatment groups received either equal volumes of normal saline or activated protein C prior to tourniquet release. Following 12h reperfusion, muscle function was assessed electrophysiologically by electrical field stimulation. The animals were then sacrificed and skeletal muscle harvested for evaluation. Activated protein C significantly attenuated skeletal muscle reperfusion injury as shown by reduced myeloperoxidase content, wet to dry ratio and electrical properties of skeletal muscle. Further in vitro work was carried out on neutrophils isolated from healthy volunteers to determine the direct effect of APC on neutrophil function. The effects of APC on TNF-alpha stimulated neutrophils were examined by measuring CD18 expression as well as reactive oxygen species generation. The in vitro work demonstrated a reduction in CD18 expression and reactive oxygen species generation. We conclude that activated protein C may have a protective role in the setting of skeletal muscle ischaemia reperfusion injury and that this is in part mediated by a direct inhibitory effect on neutrophil activation.


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