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Following ischaemia (unilateral ligation, common iliac artery) rat hindlimb muscles were examined without other intervention or following treatment with an xanthine oxidase inhibitor (allopurinol), a Na<jats:sup>+<\/jats:sup>\/H<jats:sup>+<\/jats:sup> exchange blocker (amiloride), or an oxygen free radical scavenger (vitamin E). No significant leukocyte adhesion or rolling, nor changes in capillary fine structure were observed 3 days postsurgery, when limb use was limited. However, leukocyte rolling and adhesion almost trebled by 7 days (<jats:italic>P<\/jats:italic> &lt; 0.001), when normal gait was largely restored. Capillary fine structure was disturbed over a similar time course, e.g. relative endothelial volume (control 46%, 7 days 61%; <jats:italic>P<\/jats:italic> &lt; 0.05), that resolved by 5 weeks. Where activity was increased by mild electrical stimulation 3 days after ligation muscles showed enhanced capillary swelling (endothelial volume 66%<jats:italic>versus<\/jats:italic> 50%, <jats:italic>P<\/jats:italic> &lt; 0.005), but improved fatigue index (52%<jats:italic>versus<\/jats:italic> 16%, <jats:italic>P<\/jats:italic> &lt; 0.001) as a result of greater blood flow. Muscle fatigue after ligation was related to the extent of contraction\u2010induced hyperaemia (<jats:italic>R<\/jats:italic><jats:sup>2<\/jats:sup>= 0.725), but not capillary swelling. Amiloride, and to a lesser extent allopurinol but not vitamin E, significantly decreased leukocyte rolling and adhesion, as well as capillary endothelial swelling. We conclude that increased activity of ischaemic muscles on recovery is likely to accentuate acidosis accompanying changes in microcirculation and contribute to enhanced muscle fatigue, whereas formation of oxygen free radicals may be attenuated by endogenous protective mechanisms.<\/jats:p>","DOI":"10.1113\/jphysiol.2008.158055","type":"journal-article","created":{"date-parts":[[2008,10,14]],"date-time":"2008-10-14T17:29:22Z","timestamp":1224005362000},"page":"4961-4975","source":"Crossref","is-referenced-by-count":9,"title":["Attenuation of changes in capillary fine structure and leukocyte adhesion improves muscle performance following chronic ischaemia in rats"],"prefix":"10.1113","volume":"586","author":[{"given":"O.","family":"Hudlick\u00e1","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Garnham","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R.","family":"Shiner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"Egginton","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2008,10,14]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"crossref","first-page":"1725","DOI":"10.1152\/jappl.1995.78.5.1725","article-title":"Leukocyte adhesion induced by inhibition of nitric oxide production in skeletal muscle","volume":"78","author":"Akimitsu T","year":"1995","journal-title":"J Appl Physiol"},{"key":"e_1_2_5_3_1","doi-asserted-by":"crossref","first-page":"H2757","DOI":"10.1152\/ajpheart.1997.272.6.H2757","article-title":"Capillary red blood cell flow and activation of white blood cells in chronic muscle ischemia","volume":"272","author":"Anderson SI","year":"1997","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mvr.2006.03.003"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1994.267.3.C679"},{"key":"e_1_2_5_6_1","first-page":"15","article-title":"The effect of short\u2010term and long\u2010term femoral artery ligation on rat calf muscle oxygen tension, blood flow, metabolism and function","volume":"7","author":"Angersbach D","year":"1988","journal-title":"J Microcirc Clin Exp"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1098\/rspb.1992.0019"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1971.31.4.598"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9896(200002)190:3<255::AID-PATH526>3.0.CO;2-6"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj2360461"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2362.1994.tb02061.x"},{"key":"e_1_2_5_12_1","first-page":"385","article-title":"Skeletal muscle microcirculation: the effects of limited blood flow and torbafylline","volume":"9","author":"Dawson JM","year":"1990","journal-title":"Int J Microcirc Clin Exper"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.1999.265ad.x"},{"key":"e_1_2_5_14_1","first-page":"33","article-title":"Fine structure of capillaries in ischaemic and non\u2010ischaemic rat striated muscle. 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