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

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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.

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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

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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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Authors and Affiliations

  1. Department of Cardiology, Aarhus University Hospital, Brendstrupgaardvej 100, Skejby, 8200, Aarhus N, Denmark

    M. M. Michelsen, N. B. Støttrup, M. R. Schmidt, B. Løfgren, R. V. Jensen & H. E. Bøtker

  2. Institute of Clinical Medicine, Aarhus University, Brendstrupgaardvej 100, Skejby, 8200, Aarhus N, Denmark

    M. M. Michelsen, N. B. Støttrup, M. R. Schmidt, B. Løfgren, R. V. Jensen & H. E. Bøtker

  3. Division of Cardiology, Hospital for Sick Children, Toronto, ON, M5G 1X8, Canada

    M. M. Michelsen, M. R. Schmidt, M. Tropak, E. Jean St-Michel & A. N. Redington

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  1. M. M. Michelsen
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  2. N. B. Støttrup
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Michelsen, M.M., Støttrup, N.B., Schmidt, M.R. et al. Exercise-induced cardioprotection is mediated by a bloodborne, transferable factor. Basic Res Cardiol 107, 260 (2012). https://doi.org/10.1007/s00395-012-0260-x

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  • DOI: https://doi.org/10.1007/s00395-012-0260-x

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