title: The role of prostaglandin and antioxidant availability in recovery from forearm ischemia-reperfusion injury in humans.
abstract: BACKGROUND
  Endothelial dysfunction, manifesting as attenuated flow-mediated dilation (FMD), is clinically important. Antioxidants may prevent this dysfunction; however, the acute effects of oral administration in humans are unknown. Low flow-mediated constriction (L-FMC), a further parameter of endothelial health, is largely unstudied and the mechanisms for this response unclear.
  
  
  METHODS
  Twelve healthy participants (five women and seven men) completed three test conditions: control; antioxidant cocktail (α-lipoic acid, vitamins C and E); and prostaglandin inhibitor ingestion (ibuprofen). Ultrasound measurements of brachial artery responses were assessed throughout 5 min of forearm ischemia and 3 min after. Subsequently, an ischemia-reperfusion injury was induced by a 20-min upper arm occlusion. Further, vascular function protocols were completed at 15, 30, and 45 min of recovery.
  
  
  RESULTS
  Endothelial dysfunction was evident in all conditions. FMD was attenuated at 15 min after ischemia-reperfusion injury (Pre: 6.24 ± 0.58%; Post15: 0.24 ± 0.75%; mean ± SD, P < 0.05), but recovered by 45 min. Antioxidant administration did not preserve FMD compared with control (P > 0.05). The magnitude of L-FMC was augmented at 15 min (Pre: 1.44 ± 0.27%; Post15: 3.75 ± 1.73%; P < 0.05) and recovered by 45 min. Ibuprofen administration produced the largest constrictive response (Pre: -1.13 ± 1.71%; Post15: -5.57 ± 3.82%; time × condition interaction: P < 0.05).
  
  
  CONCLUSIONS
  Results demonstrate ischemia-reperfusion injury causes endothelial dysfunction and acute oral antioxidant supplementation fails to reduce its magnitude. Our results also suggest that a lack of shear stress during occlusion combined with suppression of prostaglandin synthesis magnifies L-FMC, possibly due to augmented endothelin-1 expression.
authors.affiliation: aDepartment of Biological Sciences, University of Essex, Colchester bComparative Biomedical Sciences, Royal Veterinary College, London cCentre for Sports Medicine and Human Performance, Brunel University, Uxbridge, UK.
authors.forename: Sophie E
authors.initials: SE
authors.lastname: Carter
authors.forename: Ashton
authors.initials: A
authors.lastname: Faulkner
authors.forename: Mark
authors.initials: M
authors.lastname: Rakobowchuk
mesh_terms: D000328:Adult; D000975:Antioxidants / Q000008:administration & dosage / Q000378:metabolism; D001205:Ascorbic Acid / Q000008:administration & dosage; D001783:Blood Flow Velocity / Q000187:drug effects / Q000502:physiology; D001916:Brachial Artery / Q000000981:diagnostic imaging / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000503:physiopathology; D005260:Female; D005542:Forearm / Q000098:blood supply; D005543:Forearm Injuries / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology*; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007052:Ibuprofen / Q000008:administration & dosage; D008297:Male; D011448:Prostaglandin Antagonists / Q000008:administration & dosage; D011453:Prostaglandins / Q000502:physiology*; D015427:Reperfusion Injury / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000503:physiopathology*; D008063:Thioctic Acid / Q000008:administration & dosage; D014463:Ultrasonography; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology; D014810:Vitamin E / Q000008:administration & dosage; D055815:Young Adult
chemical_list: D000975:Antioxidants; D011448:Prostaglandin Antagonists; D011453:Prostaglandins; D014810:Vitamin E; D008063:Thioctic Acid; D001205:Ascorbic Acid; D007052:Ibuprofen