title: Atorvastatin does not affect ischaemia-induced phosphatidylserine exposition in humans in-vivo.
abstract: OBJECTIVE
  Statins can induce pharmacologic preconditioning and thereby reduce infarct size. Cellular phosphatidylserine (PS) exposition occurs in the course of ischaemia and reperfusion and has been associated with injury. In this experiment we studied the effect of atorvastatin on PS exposition after a standardised ischaemia and reperfusion challenge.
  
  
  METHODS
  In a double-blind randomised cross-over trial 30 healthy volunteers were allocated to 3 day treatment with atorvastatin (80 mg/day) and placebo (n = 24), or placebo treatment twice (n = 6). At the end of each treatment period, volunteers underwent 10 minutes of forearm ischaemic exercise. At reperfusion radiolabeled annexin A5 was administered intravenously and Gamma camera imaging of both hands was performed 1 and 4 hours after reperfusion.
  
  
  RESULTS
  Annexin A5 targeting was not different between atorvastatin treatment (26.1 ± 9.8% and 24.0 ± 9.5% respectively at 1 and 4 hours after reperfusion) and placebo treatment (25.6 ± 11.0% and 24.5 ± 10.7%) (p = 0.99). Our time control experiment did not reveal a carry-over effect.
  
  
  CONCLUSIONS
  Our results show that treatment with atorvastatin 80 mg does not reduce forearm PS exposition after ischaemic exercise. This suggests that the role of PS exposure in the prevention of ischemia and reperfusion injury by short term treatment with atorvastatin is limited.
authors.affiliation: Department of Pharmacology-Toxicology, Radboud University Nijmegen Medical Centre, The Netherlands.
authors.forename: Constantijn W
authors.initials: CW
authors.lastname: Wouters
authors.forename: Patrick
authors.initials: P
authors.lastname: Meijer
authors.forename: Carola I F
authors.initials: CI
authors.lastname: Janssen
authors.forename: Geert W J
authors.initials: GW
authors.lastname: Frederix
authors.forename: Wim J
authors.initials: WJ
authors.lastname: Oyen
authors.forename: Otto C
authors.initials: OC
authors.lastname: Boerman
authors.forename: Paul
authors.initials: P
authors.lastname: Smits
authors.forename: Gerard A
authors.initials: GA
authors.lastname: Rongen
mesh_terms: D000293:Adolescent; D000328:Adult; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D000069059:Atorvastatin; D018592:Cross-Over Studies; D004311:Double-Blind Method; D015444:Exercise; D005542:Forearm; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D007511:Ischemia / Q000517:prevention & control*; D019194:Ischemic Preconditioning; D008297:Male; D008875:Middle Aged; D010718:Phosphatidylserines / Q000378:metabolism*; D011758:Pyrroles / Q000627:therapeutic use*; D015427:Reperfusion Injury / Q000517:prevention & control*; D055815:Young Adult
chemical_list: D000924:Anticholesteremic Agents; D006538:Heptanoic Acids; D010718:Phosphatidylserines; D011758:Pyrroles; D000069059:Atorvastatin