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This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 586/20/4961    most recent jphysiol.2008.158055v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Hudlická, O. Articles by Egginton, S. PubMed PubMed Citation Articles by Hudlická, O. Articles by Egginton, S. Related Collections Cardiovascular

¹ Department of Physiology, The Medical School, University of Birmingham, Birmingham, UK
² Biomedical Sciences and Human Biology Division, School of Health Sciences, University of Wolverhampton, Wolverhampton, UK

Acute ischaemia–reperfusion disrupts capillary fine structure and increases leukocyte adhesion in postcapillary venules. We determined whether chronic muscle ischaemia has similar consequences, and whether it is possible to ameliorate its effect on muscle performance. 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⁺/H⁺ 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 (P < 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%; P < 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% versus 50%, P < 0.005), but improved fatigue index (52% versus 16%, P < 0.001) as a result of greater blood flow. Muscle fatigue after ligation was related to the extent of contraction-induced hyperaemia (R² = 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.

(Received 10 June 2008; accepted after revision 22 August 2008; first published online 28 August 2008)
Corresponding author S. Egginton: Department of Physiology, University of Birmingham Medical School, Birmingham B15 2TT, UK. Email: s.egginton{at}bham.ac.uk