{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,26]],"date-time":"2025-10-26T20:52:42Z","timestamp":1761511962262},"reference-count":52,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2006,1,1]],"date-time":"2006-01-01T00:00:00Z","timestamp":1136073600000},"content-version":"vor","delay-in-days":365,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Orthopaedic Research"],"published-print":{"date-parts":[[2005,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Trauma\u2010induced microcirculatory dysfunction, formation of free radicals and decreased endothelial release of nitric oxide (NO) contribute to evolving tissue damage following skeletal muscle injury. Administration of <jats:italic>N<\/jats:italic>\u2010acetylcysteine (NAC) known to scavenge free radicals and generate NO is considered a valuable therapeutic approach. Thus, the objective of this study was to quantitatively analyze the acute effects of NAC on skeletal muscle microcirculation and leukocyte\u2013endothelial cell interaction following severe standardized closed soft tissue injury (CSTI). Severe CSTI was induced in the hindlimbs of 14 male anesthetized Sprague\u2013Dawley rats using the controlled impact injury technique. Rats were randomly assigned (<jats:italic>n<\/jats:italic> = 7) to high\u2010dose intravenous infusion of NAC (400 mg\/kg body weight) or isovolemic normal saline (NS). Non\u2010injured, sham\u2010operated animals (<jats:italic>n<\/jats:italic> = 1) were subjected to the same surgical procedures but did not receive any additional fluid. Creatin kinase (CK) activity was assessed at baseline, 1 h before and 2 h following posttraumatic NAC or NS infusion. Microcirculation of the extensor digitorum longus (EDL) muscle was analyzed using intravital microscopy and Laser\u2010Doppler flowmetry (LDF). Edema index (EI) was calculated by measuring the EDL wet\u2010to\u2010dry weight ratio (EI = injured\/contralateral limb). EDL\u2010muscles were analyzed for desmin immunoreactivity and granulocyte infiltration. Microvascular deteriorations observed following NS\u2010infusion were effectively reversed by NAC: Functional capillary density was restored to levels found in sham\u2010operated animals and leukocyte adherence was significantly (<jats:italic>p<\/jats:italic> &lt; 0.05) reduced compared to the NS group. NAC significantly (<jats:italic>p<\/jats:italic> &lt; 0.05) increased erythrocyte flux determined by Laser\u2010Doppler flowmetry. Posttraumatic serum CK levels and EI were significantly (<jats:italic>p<\/jats:italic> &lt; 0.05) decreased by NAC. During the posttraumatic acute phase, single infusion of NAC markedly reduced posttraumatic microvascular dysfunction, attenuated both leukocyte adherence and tissue infiltration. NAC also decreased CSTI\u2010induced edema formation and myonecrosis as reflected by attenuated serum CK levels and attenuated loss of desmin immunoreactivity. NAC may serve as an effective therapeutic strategy by supporting microvascular blood supply and tissue viability in the early posttraumatic period. Additional studies aimed at long\u2010term analysis and investigation of injury severity\u2014or dosage dependency are needed. \u00a9 2004 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved.<\/jats:p>","DOI":"10.1016\/j.orthres.2004.05.009","type":"journal-article","created":{"date-parts":[[2004,7,8]],"date-time":"2004-07-08T03:50:17Z","timestamp":1089258617000},"page":"231-241","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Acute effects of <i>N<\/i>\u2010acetylcysteine on skeletal muscle microcirculation following closed soft tissue trauma in rats"],"prefix":"10.1002","volume":"23","author":[{"given":"Klaus\u2010D.","family":"Schaser","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Herman J.","family":"Bail","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lioba","family":"Schewior","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John F.","family":"Stover","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ingo","family":"Melcher","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Norbert P.","family":"Haas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Mittlmeier","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2006,1]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4615-5865-1_63"},{"key":"e_1_2_1_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/0891-5849(89)90066-X"},{"key":"e_1_2_1_4_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1972.sp009808"},{"key":"e_1_2_1_5_2","first-page":"H1504","article-title":"Molecular determinants of shear rate\u2010dependent leukocyte adhesion in postcapillary venules","volume":"33","author":"Bienvenu K","year":"1993","journal-title":"Am J Physiol"},{"key":"e_1_2_1_6_2","doi-asserted-by":"publisher","DOI":"10.1364\/AO.20.002097"},{"key":"e_1_2_1_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(82)90301-X"},{"key":"e_1_2_1_8_2","doi-asserted-by":"publisher","DOI":"10.1001\/archsurg.136.10.1201"},{"key":"e_1_2_1_9_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.1998.274.3.R822"},{"key":"e_1_2_1_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(199807)41:7<1141::AID-ART2>3.0.CO;2-S"},{"key":"e_1_2_1_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(00)00018-3"},{"key":"e_1_2_1_12_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.00-0526hyp"},{"key":"e_1_2_1_13_2","doi-asserted-by":"publisher","DOI":"10.1097\/00007890-199404270-00004"},{"key":"e_1_2_1_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/0891-5849(88)90115-3"},{"key":"e_1_2_1_15_2","doi-asserted-by":"publisher","DOI":"10.1097\/00007890-199501150-00002"},{"key":"e_1_2_1_16_2","unstructured":"HansenST.Soft\u2010tissue injuries in the lower extremity. 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