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Activated protein C attenuates acute ischaemia reperfusion injury in skeletal muscle
Author(s) -
Dillon J. P.,
Laing A. J.,
Cahill R. A.,
O'Brien G. C.,
Street J. T.,
Wang J. H.,
Mc Guinness A.,
Redmond H. P.
Publication year - 2005
Publication title -
journal of orthopaedic research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.041
H-Index - 155
eISSN - 1554-527X
pISSN - 0736-0266
DOI - 10.1016/j.orthres.2005.04.009.1100230631
Subject(s) - skeletal muscle , reperfusion injury , ischemia , cardiology , medicine , chemistry , pharmacology
An Erratum has been published for this article in Journal of Orthopaedic Research 24: 576–576, 2006 . Activated 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 2 h followed by 12 h reperfusion. Treatment groups received either equal volumes of normal saline or activated protein C prior to tourniquet release. Following 12 h 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‐α 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. © 2005 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved.