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The remote ischemic preconditioning algorithm: effect of number of cycles, cycle duration and effector organ mass on efficacy of protection

  • Jacob Johnsen
  • Kasper Pryds
  • Rasha Salman
  • Bo Løfgren
  • Steen Buus Kristiansen
  • Hans Erik Bøtker
Original Contribution

Abstract

Remote ischemic preconditioning (rIPC), induced by cycles of transient limb ischemia and reperfusion (IR), is cardioprotective. The optimal rIPC-algorithm is not established. We investigated the effect of cycle numbers and ischemia duration within each rIPC-cycle and the influence of effector organ mass on the efficacy of cardioprotection. Furthermore, the duration of the early phase of protection by rIPC was investigated. Using a tourniquet tightened at the inguinal level, we subjected C57Bl/6NTac mice to intermittent hind-limb ischemia and reperfusion. The rIPC-protocols consisted of (I) two, four, six or eight cycles, (II) 2, 5 or 10 min of ischemia in each cycle, (III) single or two hind-limb occlusions and (IV) 0.5, 1.5, 2.0 or 2.5 h intervals from rIPC to index cardiac ischemia. All rIPC algorithms were followed by 5 min of reperfusion. The hearts were subsequently exposed to 25 min of global ischemia and 60 min of reperfusion in an ex vivo Langendorff model. Cardioprotection was evaluated by infarct size and post-ischemic hemodynamic recovery. Four to six rIPC cycles yielded significant cardioprotection with no further protection by eight cycles. Ischemic cycles lasting 2 min offered the same protection as cycles of 5 min ischemia, whereas prolonged cycles lasting 10 min abrogated protection. One and two hind-limb preconditioning were equally protective. In our mouse model, the duration of protection by rIPC was 1.5 h. These findings indicate that the number and duration of cycles rather than the tissue mass exposed to rIPC determines the efficacy of rIPC.

Keywords

Cardioprotection Ischemia–reperfusion Remote ischemic conditioning Preconditioning Infarct size 

Notes

Acknowledgments

We thank Casper Carlsen Elkjær and Anja Helveg Larsen for excellent technical assistance. This study was supported financially by the Danish Heart Foundation, The Danish Strategic Research Council (11-1115818), The Beckett Foundation and the Institute of Clinical Medicine, Aarhus University.

Compliance with ethical standards

Conflict of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Jacob Johnsen
    • 1
    • 2
  • Kasper Pryds
    • 1
    • 2
  • Rasha Salman
    • 1
    • 2
  • Bo Løfgren
    • 1
    • 2
  • Steen Buus Kristiansen
    • 1
    • 2
  • Hans Erik Bøtker
    • 1
    • 2
  1. 1.Department of CardiologyAarhus University HospitalAarhus NDenmark
  2. 2.Department of Clinical MedicineAarhus UniversityAarhusDenmark

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