{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T20:36:21Z","timestamp":1789504581935,"version":"build-2803163510"},"reference-count":44,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","license":[{"start":{"date-parts":[[2018,12,1]],"date-time":"2018-12-01T00:00:00Z","timestamp":1543622400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Objectives:<\/jats:title>\n            <jats:p>Compartment syndrome (CS) is one of the most devastating consequences of musculoskeletal trauma. The pathophysiology of CS includes elevation of intracompartmental pressure (ICP), causing damage to the microcirculation, decreased oxygen delivery, tissue anoxia, and cell death. CS is a combined ischemic and inflammatory condition that induces the systemic inflammatory cascade. In complete ischemia, within the first hour of reperfusion, a peak in the pro-inflammatory cytokine, tumor necrosis factor alpha (TNF-\u03b1) has been previously reported. The purpose of this study was to examine the suspected systemic inflammatory cytokine\/chemokine release in response to CS, and to evaluate the microvascular dysfunction, tissue injury, and inflammatory response following the neutralization of pro-inflammatory cytokines TNF-\u03b1 and\/or interleukin-1 beta (IL-1\u03b2).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods:<\/jats:title>\n            <jats:p>Twenty-eight male Wistar rats were randomly assigned into 5 groups: Sham (no CS), CS (with isotype control), CS+TNF-\u03b1 neutralizing antibody (NA), CS+IL-1\u03b2 NA, CS+Combo (both TNF-\u03b1 and IL-1\u03b2 NA). CS was induced by elevation of ICP above 30\u200amm Hg through an infusion of isotonic saline into the anterior compartment of the hind limb for 2 hours; NA were administered just prior to fasciotomy. Microvascular perfusion, cellular tissue injury, and inflammatory response within the extensor digitorum longus muscle were assessed using intravital video microscopy for 45 minutes after fasciotomy. Systemic levels of 24 different cytokines\/chemokines were also measured, using the xMAP Luminex technology.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results:<\/jats:title>\n            <jats:p>Of the 24\u200acytokines\/chemokines sampled, 6 were significantly elevated from their baseline levels, and included the pro-inflammatory cytokines TNF-\u03b1, IL-1\u03b2, growth-related oncogene\/keratinocyte chemoattractant (GRO\/KC), monocyte chemoattractant protein 1 (MCP-1), macrophage inflammatory protein 1 alpha (MIP-1\u03b1), and the anti-inflammatory cytokine IL-10. CS resulted in a significant decrease in microvascular perfusion, from 75\u200a\u00b1\u200a2% continuously perfused capillaries in the sham to 31\u200a\u00b1\u200a4% in CS (<jats:italic toggle=\"yes\">P\u200a&lt;\u200a<\/jats:italic>.001), a significant increase in tissue injury (0.33\u200a\u00b1\u200a0.4 versus 0.04\u200a\u00b1\u200a0.01 in sham) and leukocyte activation (14\u200a\u00b1\u200a2 adherent leukocytes\/1000\u200a\u03bcm<jats:sup>2<\/jats:sup> versus 2\u200a\u00b1\u200a1 adherent leukocytes\/100\u200a\u03bcm<jats:sup>2<\/jats:sup> in sham, <jats:italic toggle=\"yes\">P\u200a&lt;\u200a<\/jats:italic>.001). CS-associated tissue injury was significantly decreased with TNF-\u03b1 neutralization (<jats:italic toggle=\"yes\">P\u200a&lt;\u200a<\/jats:italic>.05), both when administered alone or in combination with IL-1\u03b2 (<jats:italic toggle=\"yes\">P\u200a&lt;\u200a<\/jats:italic>.05). Additionally, TNF-\u03b1 neutralization blocked CS-associated leukocyte activation (<jats:italic toggle=\"yes\">P\u200a&lt;\u200a<\/jats:italic>.05); IL-1\u03b2 neutralization also diminished leukocyte adhesion (<jats:italic toggle=\"yes\">P\u200a&lt;\u200a<\/jats:italic>.05). Perfusion remained virtually unchanged in CS animals treated with NA (36\u200a\u00b1\u200a4%, 32\u200a\u00b1\u200a3% and 30\u200a\u00b1\u200a2% in CS+TNF-\u03b1, CS+IL-1\u03b2 and CS+Combo groups, respectively).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion:<\/jats:title>\n            <jats:p>The results of this study indicate that CS induces a systemic inflammation, as evidenced by upregulation of inflammatory cytokines\/chemokines in circulation. Neutralization of TNF-\u03b1 led to a significant reduction in tissue injury; however, it had no effect on the CS-induced microvascular dysfunction. This suggests a distinct role of TNF-\u03b1 in the pathophysiology of muscle injury in CS.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1097\/oi9.0000000000000011","type":"journal-article","created":{"date-parts":[[2021,1,16]],"date-time":"2021-01-16T07:05:43Z","timestamp":1610780743000},"page":"e011","source":"Crossref","is-referenced-by-count":2,"title":["Compartment syndrome-induced muscle injury is diminished by the neutralization of pro-inflammatory cytokines"],"prefix":"10.1097","volume":"1","author":[{"given":"Erin","family":"Donohoe","sequence":"first","affiliation":[{"name":"Division of Orthopaedic Surgery, University of Western Ontario"},{"name":"Centre for Critical Illness Research, Lawson Health Research Institute, London, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aurelia","family":"Bihari","sequence":"additional","affiliation":[{"name":"Division of Orthopaedic Surgery, University of Western Ontario"},{"name":"Centre for Critical Illness Research, Lawson Health Research Institute, London, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emil","family":"Schemitsch","sequence":"additional","affiliation":[{"name":"Division of Orthopaedic Surgery, University of Western Ontario"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Sanders","sequence":"additional","affiliation":[{"name":"Division of Orthopaedic Surgery, University of Western Ontario"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdel-Rahman","family":"Lawendy","sequence":"additional","affiliation":[{"name":"Division of Orthopaedic Surgery, University of Western Ontario"},{"name":"Centre for Critical Illness Research, Lawson Health Research Institute, London, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"R1-20230823","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1097\/00003086-197511000-00003","article-title":"Compartmental syndrome. 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