title: Heme arginate improves reperfusion patterns after ischemia: a randomized, placebo-controlled trial in healthy male subjects.
abstract: BACKGROUND
  Heme arginate can induce heme oxygenase-1 to protect tissue against ischemia-reperfusion injury. Blood oxygen level dependent (BOLD) functional magnetic resonance imaging measures changes in tissue oxygenation with a high spatial and temporal resolution. BOLD imaging was applied to test the effect of heme arginate on experimental ischemia reperfusion injury in the calf muscles.
  
  
  METHODS
  A two period, controlled, observer blinded, crossover trial was performed in 12 healthy male subjects. Heme arginate (1 mg/kg body weight) or placebo were infused 24 h prior to a 20 min leg ischemia induced by a thigh cuff. 3 Tesla BOLD-imaging of the calf was performed and signal time courses from soleus, gastrocnemius and tibialis anterior muscle were available from 11 participants for technical reasons.
  
  
  RESULTS
  Peak reactive hyperemia signal of the musculature was significantly increased and occurred earlier after heme arginate compared to placebo (106.2 ± 0.6% at 175 ± 16s vs. 104.5 ± 0.6% at 221 ± 19s; p = 0.025 for peak reperfusion and p = 0.012 for time to peak).
  
  
  CONCLUSIONS
  A single high dose of heme arginate improves reperfusion patterns during ischemia reperfusion injury in humans. BOLD sensitive, functional MRI is applicable for the assessment of experimental ischemia reperfusion injury in skeletal muscle.
authors.affiliation: Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria.
authors.forename: Martin
authors.initials: M
authors.lastname: Andreas
authors.forename: Albrecht Ingo
authors.initials: AI
authors.lastname: Schmid
authors.forename: Daniel
authors.initials: D
authors.lastname: Doberer
authors.forename: Kiril
authors.initials: K
authors.lastname: Schewzow
authors.forename: Stefan
authors.initials: S
authors.lastname: Weisshaar
authors.forename: Georg
authors.initials: G
authors.lastname: Heinze
authors.forename: Martin
authors.initials: M
authors.lastname: Bilban
authors.forename: Ewald
authors.initials: E
authors.lastname: Moser
authors.forename: Michael
authors.initials: M
authors.lastname: Wolzt
mesh_terms: D000293:Adolescent; D000328:Adult; D001120:Arginine / Q000008:administration & dosage*; D018592:Cross-Over Studies; D005500:Follow-Up Studies; D006418:Heme / Q000008:administration & dosage*; D006419:Heme Oxygenase (Decyclizing); D006801:Humans; D007262:Infusions, Intravenous; D007511:Ischemia / Q000175:diagnosis* / Q000188:drug therapy / Q000378:metabolism; D007866:Leg / Q000098:blood supply*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism; D010101:Oxygen Consumption; D011446:Prospective Studies; D012016:Reference Values; D015427:Reperfusion Injury / Q000175:diagnosis / Q000378:metabolism / Q000517:prevention & control*; D016037:Single-Blind Method; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D006418:Heme; D001120:Arginine; D006419:Heme Oxygenase (Decyclizing); C048849:heme arginate