title: Early assessment of skeletal muscle damage after ischaemia-reperfusion injury using Tc-99m-glucarate.
abstract: OBJECTIVE
  After acute arterial obstruction of the lower extremity, muscle damage is the critical determinant for clinical outcome. The extent of muscle damage and limb viability are currently assessed by clinical examination, which is inaccurate. Tc-99m-pyrophosphate (PYP) has been applied for imaging ischaemia-reperfusion damage. More recently, a new imaging agent, Tc-99m-glucarate (GLUC), was introduced for delineating early myocardial infarction after ischaemia-reperfusion. The aim of this study was to determine if GLUC could delineate early skeletal muscle damage after ischaemia-reperfusion. Both tracers were used in a novel murine model of hindlimb ischaemia-reperfusion.
  
  
  METHODS
  In anaesthetised mice, ischaemia of one hindlimb was maintained for 2, 3 and 4h using a tourniquet, followed by a reperfusion period of 1h. Additionally, reperfusion periods of 3, 24 and 96h were studied after 3h of ischaemia. PYP or GLUC was injected 45min before end of reperfusion. Concentrations of both agents were determined in blood, reperfused and contralateral muscle. Reperfused-to-contralateral muscle ratios were calculated. In separate experiments, muscle biopsies were obtained for histologic examination.
  
  
  RESULTS
  Ischaemia and reperfusion damage was demonstrated histologically. Using scintigraphy GLUC depicted reperfusion significantly better than PYP. After 2, 3 and 4h of ischaemia, the reperfused-to-contralateral ratios for GLUC were 10.7+/-0.9, 8.9+/-0.9 and 8.6+/-1.1, as compared to 4.5+/-0.7, 4.9+/-0.4 and 4.5+/-0.4 for PYP (P<0.05 at all points). For longer periods of reperfusion, the ratios for GLUC decreased to similar levels as observed for PYP.
  
  
  CONCLUSIONS
  The present study indicates that GLUC is a specific early marker of myocyte necrosis after ischaemia-reperfusion. GLUC may become an useful agent for clinical, early, non-invasive monitoring of skeletal muscle damage after ischaemia-reperfusion.
authors.affiliation: Department of Surgery, St Radboud University Hospital, Nijmegen, The Netherlands.
authors.forename: A M
authors.initials: AM
authors.lastname: Wiersema
authors.forename: W J
authors.initials: WJ
authors.lastname: Oyen
authors.forename: R
authors.initials: R
authors.lastname: Dirksen
authors.forename: A A
authors.initials: AA
authors.lastname: Verhofstad
authors.forename: F H
authors.initials: FH
authors.lastname: Corstens
authors.forename: J A
authors.initials: JA
authors.lastname: van der Vliet
mesh_terms: D000818:Animals; D005937:Glucaric Acid / Q000031:analogs & derivatives*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000000981:diagnostic imaging* / Q000473:pathology*; D009336:Necrosis; D015609:Organotechnetium Compounds; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals; D015427:Reperfusion Injury / Q000000981:diagnostic imaging* / Q000473:pathology*
chemical_list: D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; C067171:technetium Tc 99m glucarate; D005937:Glucaric Acid