title: Altered endothelin-1 levels in acute lower limb ischemia and reperfusion.
abstract: Tourniquet-induced ischemia is often used in orthopedic and reconstructive procedures. This is associated with muscle damage and dysfunction, which limits tourniquet application time. Endothelin-1 (ET-1) is a potent vasoconstrictor, which has been implicated in ischemic conditions and ischemia-reperfusion injury. This study aimed to investigate the role of ET-1 in human skeletal muscle subjected to tourniquet-induced acute ischemia and reperfusion. Thirteen patients undergoing total knee replacement were studied. Plasma and muscle ET-1 concentrations were measured at the start of surgery, after an hour of acute ischemia, and 15 minutes following reperfusion. ET-1 receptor binding was also studied by use of autoradiography, and ET-1 mRNA expression investigated by use of real-time polymerase chain reaction (RT-PCR). Tissue ET-1 increased following the period of acute ischemia and persisted during reperfusion. ET-1 was associated with microvessels and macrophages in the muscle. No changes in circulating ET-1 levels, ET-1 mRNA expression, or ET-1 receptor binding were found. It is concluded that the ET-1 pathway is involved in acute ischemia and reperfusion and it may contribute to the muscle injury that occurs during surgical procedures.
authors.affiliation: Department of Surgery, Royal Free and University College Medical School, Royal Free Campus, London, UK. jcstsui@hotmail.com
authors.forename: J C S
authors.initials: JC
authors.lastname: Tsui
authors.forename: D M
authors.initials: DM
authors.lastname: Baker
authors.forename: E
authors.initials: E
authors.lastname: Biecker
authors.forename: S
authors.initials: S
authors.lastname: Shaw
authors.forename: M R
authors.initials: MR
authors.lastname: Dashwood
mesh_terms: D000208:Acute Disease; D000368:Aged; D000369:Aged, 80 and over; D019645:Arthroplasty, Replacement, Knee; D001345:Autoradiography; D003627:Data Interpretation, Statistical; D019332:Endothelin-1 / Q000032:analysis / Q000037:antagonists & inhibitors / Q000097:blood / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007511:Ischemia / Q000378:metabolism / Q000503:physiopathology*; D007866:Leg / Q000098:blood supply*; D008264:Macrophages / Q000502:physiology; D008297:Male; D008833:Microcirculation; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000737:chemistry / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D017466:Receptors, Endothelin / Q000378:metabolism; D015424:Reperfusion; D013997:Time Factors; D014111:Tourniquets
chemical_list: D019332:Endothelin-1; D012333:RNA, Messenger; D017466:Receptors, Endothelin