title: Lower limb ischemia-reperfusion injury triggers a systemic inflammatory response and multiple organ dysfunction.
abstract: Restoration of blood flow to an acutely ischemic lower limb may, paradoxically, result in systemic complications and unexpected mortality. We investigated the effect of acute ischemia-perfusion of the lower limb on cytokine production and end organ function. Plasma concentrations of tumor necrosis factor-alpha (TNF-a) and interleukin-6 (IL-6) were determined in five groups of male Wistar rats: control, 3 hours of bilateral hind limb ischemia alone, and 3 hours of bilateral hind limb ischemia followed by 1 hour, 2 hours, or 3 hours of reperfusion, respectively. In a second experiment, the effect of lower limb ischemia-reperfusion on remote organs (lung, liver, and kidney) was assessed biochemically and histologically. There was a significant increase in plasma concentrations of TNF-a in plasma of animals subjected to 3 hours of bilateral hind limb ischemia followed by 1 hour of reperfusion, 40.1 +/- 4.4 pg/ml, when compared with controls, 22.6 +/- 4.4 pg/ml, or animals in the ischemia-alone group, 16.3 +/- 5.2 (p <0.05). Plasma concentration of IL-6 increased progressively and significantly in animals subjected to bilateral hind limb ischemia followed by 1 hour of reperfusion, 720 +/- 107 pg/ml; 2 hours of reperfusion, 1987 +/- 489 pg/ml; or 3 hours of reperfusion, 6284 +/- 1244 (p <0.0001), compared with controls, 104 +/- 43 pg/ml; or animals in the ischemia-alone group, 140 +/- 55 pg/ml. In the study comparing portal and systemic concentrations of IL-6, systemic concentrations of IL-6, 967 +/- 184 pg/ml were significantly higher than those in the portal circulation 577 +/- 127 pg/ml (p <0.05). There was a significant increase in plasma concentrations of urea, creatinine, aspartate transaminase, alanine transaminase, and lactic dehydrogenase in reperfused animals compared with controls (p <0.001). Morbidity and mortality following reperfusion of the acutely ischemic limb may be a manifestation of multiple organ dysfunction caused by a systemic inflammatory response triggered by reperfusion of the ischemic extremities.
authors.affiliation: Department of Surgery, The Queen's University of Belfast, Institute of Clinical Sciences, Grosvenor Road, Belfast BT12 6BJ, Northern Ireland, UK.
authors.forename: Magdi M I
authors.initials: MM
authors.lastname: Yassin
authors.forename: Denis W
authors.initials: DW
authors.lastname: Harkin
authors.forename: Aires A B
authors.initials: AA
authors.lastname: Barros D'Sa
authors.forename: M Isla
authors.initials: MI
authors.lastname: Halliday
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Rowlands
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D006614:Hindlimb / Q000098:blood supply* / Q000276:immunology*; D015850:Interleukin-6 / Q000097:blood; D007668:Kidney / Q000276:immunology / Q000473:pathology; D008099:Liver / Q000276:immunology / Q000473:pathology; D008168:Lung / Q000276:immunology / Q000473:pathology; D008297:Male; D009102:Multiple Organ Failure / Q000097:blood / Q000209:etiology* / Q000276:immunology*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000097:blood / Q000150:complications* / Q000276:immunology*; D018746:Systemic Inflammatory Response Syndrome / Q000097:blood / Q000209:etiology* / Q000276:immunology*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha