Atorvastatin does not Affect Ischaemia-Induced Phosphatidylserine Exposition in Humans in-vivo

Constantijn W. Wouters; Patrick Meijer; Carola I.F. Janssen; Geert W.J. Frederix; Wim J. Oyen; Otto C. Boerman; Paul Smits; Gerard A. Rongen

doi:10.5551/jat.10983

Original Article

Atorvastatin does not Affect Ischaemia-Induced Phosphatidylserine Exposition in Humans in-vivo

Constantijn W. Wouters, Patrick Meijer, Carola I.F. Janssen, Geert W.J. Frederix, Wim J. Oyen, Otto C. Boerman, Paul Smits, Gerard A. Rongen

Author information

Constantijn W. Wouters
Department of Pharmacology-Toxicology, Radboud University Nijmegen Medical Centre.
Department of Cardiology, Radboud University Nijmegen Medical Centre.
Patrick Meijer
Department of Pharmacology-Toxicology, Radboud University Nijmegen Medical Centre.
Department of Anaesthesiology, Radboud University Nijmegen Medical Centre.
Carola I.F. Janssen
Department of Pharmacology-Toxicology, Radboud University Nijmegen Medical Centre.
Geert W.J. Frederix
Department of Pharmacology-Toxicology, Radboud University Nijmegen Medical Centre.
Wim J. Oyen
Department of Nuclear Medicine, Radboud University Nijmegen Medical Centre.
Otto C. Boerman
Department of Nuclear Medicine, Radboud University Nijmegen Medical Centre.
Paul Smits
Department of Pharmacology-Toxicology, Radboud University Nijmegen Medical Centre.
Department of General Internal Medicine, Radboud University Nijmegen Medical Centre.
Gerard A. Rongen
Department of Pharmacology-Toxicology, Radboud University Nijmegen Medical Centre.
Department of General Internal Medicine, Radboud University Nijmegen Medical Centre.

Keywords: Atorvastatin, Ischaemia-reperfusion injury, Phosphatidylserines, Annexin A5 scintigraphy, Pharmacologic preconditioning

JOURNAL OPEN ACCESS

2012 Volume 19 Issue 3 Pages 285-291

DOI https://doi.org/10.5551/jat.10983

View "Advance Publication" version (December 7, 2011).

Details

Abstract

Aim: 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.

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