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Exercise-induced cardioprotection is mediated by a bloodborne, transferable factor

  • M. M. Michelsen
  • N. B. Støttrup
  • M. R. Schmidt
  • B. Løfgren
  • R. V. Jensen
  • M. Tropak
  • E. Jean St-Michel
  • A. N. Redington
  • H. E. Bøtker
Original Contribution

Abstract

Exercise protects against myocardial ischemia-reperfusion (I-R) injury but the mechanism remains unclear. Protection can be transferred from a remotely preconditioned human donor to an isolated perfused rabbit heart using a dialysate of plasma. We hypothesized that physical exercise preconditioning also confers cardioprotection through a humorally mediated effector dependent on opioid receptor activation. Thirteen male volunteers performed vigorous exercise (four 2-minute bouts of high-intensity exercise) and 1 week later they underwent remote ischemic preconditioning (four cycles of 5 min upper limb ischemia and reperfusion). Dialysates were prepared from blood collected before (control) and after the two interventions. Isolated rabbit hearts were perfused with the dialysates without and with co-administration of naloxone (opioid receptor antagonist) prior to 40 min regional ischemia and 2 h reperfusion. Exercise and remote ischemic preconditioning (rIPC) reduced infarct size from 60 ± 5 to 35 ± 5 % and from 57 ± 7 to 27 ± 3 % of the area at risk, respectively (p < 0.05 and < 0.01). Furthermore, post-ischemic left ventricular developed pressure was improved compared with controls (p = 0.08 for exercise and p = 0.04 for rIPC). Co-perfusion with naloxone abrogated the protective effects of exercise and remote ischemic preconditioned dialysates. In conclusion, high-intensity exercise preconditioning elicits cardioprotection through a humorally mediated dependent on opioid receptor activation, similar to rIPC.

Keywords

Ischemia Reperfusion Cardioprotection Exercise Remote ischemic preconditioning Humoral factor 

Abbreviations

CAD

Coronary artery disease

IPC

Ischemic preconditioning

RIPC

Remote IPC

ExPC

Exercise preconditioning

IS

Infarct size

IPC

Ischemic preconditioning

I-R

Ischemia-reperfusion

KH-buffer

Krebs Henseleit buffer

LV

Left ventricular

LVDP

Left ventricular developed pressure

Notes

Acknowledgments

We thank Eva Sparrewath and Bente Jacobsen for excellent technical assistance. The results of the present study do not constitute endorsement by ACSM. This study was financially supported by Foundation Leducq (CVD 06), The Danish Agency for Science, Technology and Innovation (11-108354 and 11-115818), Canadian Institutes of Health Research, The Lundbeck Foundation

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Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • M. M. Michelsen
    • 1
    • 2
    • 3
  • N. B. Støttrup
    • 1
    • 2
  • M. R. Schmidt
    • 1
    • 2
    • 3
  • B. Løfgren
    • 1
    • 2
  • R. V. Jensen
    • 1
    • 2
  • M. Tropak
    • 3
  • E. Jean St-Michel
    • 3
  • A. N. Redington
    • 3
  • H. E. Bøtker
    • 1
    • 2
  1. 1.Department of CardiologyAarhus University HospitalAarhus NDenmark
  2. 2.Institute of Clinical MedicineAarhus UniversityAarhus NDenmark
  3. 3.Division of CardiologyHospital for Sick ChildrenTorontoCanada

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