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Plasma from remotely conditioned pigs reduces infarct size when given before or after ischemia to isolated perfused rat hearts

  • Integrative physiology
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Abstract

Short cycles of ischemia/reperfusion in a tissue/organ remote from the heart reduce myocardial ischemia/reperfusion injury. Such remote ischemic conditioning (RIC) can be induced before (pre-), during (per-), or after (post-) the onset of myocardial ischemia. RIC’s protection can be transferred with plasma between different individuals, even across species. Infusion of plasma from pigs with remote ischemic per-conditioning(RPERC) reduces infarct size in isolated perfused rat hearts when given before and after the index ischemia. We here determined whether or not infusion of pig plasma is equally protective when given exclusively before or after the index ischemia in isolated perfused rat hearts. Blood was sampled at 10 min reperfusion from Göttingen mini-pigs with 60/180 min coronary occlusion/reperfusion without (placebo, n = 8) or with RPERC (4 × 5 min/5 min hindlimb ischemia/reperfusion, n = 7) starting at 20 min coronary occlusion. Plasma was separated, diluted (1:6), and infused into isolated perfused rat hearts before (plasmabefore) or after (plasmaafter) 30/120 min global zero-flow ischemia/reperfusion. Infarct size (IS) was demarcated and calculated as percent of ventricular mass (means ± standard deviations). The activation of cardioprotective intracellular signaling cascades was analyzed by Western blot. RPERC-plasma reduced IS (placebo-plasmabefore 36 ± 5% and placebo-plasmaafter 36 ± 7% versus RPERC-plasmabefore 19 ± 3% and RPERC-plasmaafter 21 ± 4%; P < 0.001 versus placebo-plasma) and increased the phosphorylation of signal transducer and activator of transcription 3, no matter whether plasma was given before ischemia or during reperfusion. Obviously, the protection, which the released factors exert, is operative during reperfusion. However, pre-ischemic exposure to such cardioprotective factors is remembered throughout ischemia.

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Data availability

The datasets generated and analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgments

The technical assistance of Julia Husmann, Marion Pesch, Amelie Irmert, and Sandra Krüger is gratefully acknowledged.

Funding

The present study was financially supported by German Research Foundation (DFG; SFB 1116 B08).

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Authors and Affiliations

  1. Institute for Pathophysiology, West German Heart and Vascular Center, University of Essen Medical School, Hufelandstr. 55, 45122, Essen, Germany

    Helmut Raphael Lieder, Andreas Skyschally, Gerd Heusch & Petra Kleinbongard

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  1. Helmut Raphael Lieder
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  2. Andreas Skyschally
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  3. Gerd Heusch
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  4. Petra Kleinbongard
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Contributions

Conceived and designed the study: H.R.L., G.H., P.K.

Performed the experiments: H.R.L., A.S., P.K.

Analyzed data: H.R.L., A.S.

Wrote the paper: H.R.L., P.K.

Critically revised the manuscript: G.H.

Corresponding author

Correspondence to Petra Kleinbongard.

Ethics declarations

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed, and all procedures performed in animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted. The experimental protocols were approved by the Bioethical Committee of the North Rhine Westphalia State Environment Agency (LANUV NRW, Germany: G1407/14, Z1493-15 and G1655/18).

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The authors declare that they have no conflict of interest.

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A commentary to this article is available online at https://doi.org/10.1007/s00424-019-02315-x

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Lieder, H.R., Skyschally, A., Heusch, G. et al. Plasma from remotely conditioned pigs reduces infarct size when given before or after ischemia to isolated perfused rat hearts. Pflugers Arch - Eur J Physiol 471, 1371–1379 (2019). https://doi.org/10.1007/s00424-019-02314-y

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