Intensive Care Medicine

, 37:1525 | Cite as

Comparison of carbamylated erythropoietin-FC fusion protein and recombinant human erythropoietin during porcine aortic balloon occlusion-induced spinal cord ischemia/reperfusion injury

  • Florian Simon
  • Angelika Scheuerle
  • Michael Gröger
  • Brigitta Vcelar
  • Oscar McCook
  • Peter Möller
  • Michael Georgieff
  • Enrico Calzia
  • Peter Radermacher
  • Hubert Schelzig
Experimental
First Online:
Received:
Accepted:

Abstract

Purpose

Recombinant human erythropoietin (rhEPO) attenuated ischemia/reperfusion (I/R) injury-induced spinal cord damage. Since carbamylated EPO derivatives are stated to be devoid of rhEPO side effects, we tested the hypothesis that a newly developed carbamylated EPO-FC fusion protein (cEPO-FC) would compare favorably with rhEPO.

Methods

Anesthetized and mechanically ventilated pigs randomly received cEPO-FC (50 μg kg−1), rhEPO (5,000 IU kg−1) or vehicle (n = 9 per group) 30 min prior to 30 min of aortic occlusion and over the 4 h of reperfusion. During aortic occlusion, mean arterial pressure (MAP) was maintained at 80–120% of baseline values by esmolol, nitroglycerin, and adenosine-5′-triphosphate (ATP). During reperfusion, noradrenaline was titrated to keep MAP at pre-ischemic levels. Spinal cord function was assessed by motor evoked potentials (MEP) and lower limb reflexes. Tissue damage was evaluated using hematoxylin and eosin, Nissl, and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) staining. Plasma levels of interleukin-6, tumor necrosis factor-α, and 8-isoprostanes were measured as markers of systemic inflammation and oxidative stress.

Results

While only cEPO-FC restored MEP amplitude to values close to pre-occlusion levels, both cEPO-FC and rhEPO comparably restored lower limb reflexes and reduced the percentage of damaged neurons. Infiltration of mononuclear inflammatory cells was moderate without intergroup difference; positive TUNEL staining was barely detectable in any group. I/R injury increased blood cytokine levels without intergroup difference, whereas both cEPO-FC and rhEPO significantly lowered 8-isoprostane levels.

Conclusions

In a porcine model of aortic balloon occlusion-induced spinal cord I/R injury, cEPO-FC and rhEPO comparably protected against ischemic spinal cord dysfunction and neuronal damage. This effect coincided with attenuated oxidative stress.

Keywords

Motor evoked potentials Lower limb reflexes Nissl staining TUNEL staining Cytokines 8-Isoprostanes 
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Notes

Acknowledgment

This study was supported by the Deutsche Forschungsgemeinschaft (DFG Sche 899/2-3). Carbamylated erythropoietin fusion protein (cEPO-FC) was kindly provided by Polymun Scientific GmbH, Vienna, Austria. The authors are indebted to Andrea Söll and Tanja Schulz for skillful assistance.

Conflicts of interest

B. Vcelar is an employee responsible for preclinical research at Polymun Scientific GmbH (Vienna, Austria), a company involved in the commercial development of cEPO-FC, but holds no equity in that company nor related to the molecules investigated. The other authors declare that they have no competing interests at all.

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Copyright information

© Copyright jointly held by Springer and ESICM 2011

Authors and Affiliations

  • Florian Simon
    • 1
    • 2
  • Angelika Scheuerle
    • 3
  • Michael Gröger
    • 2
  • Brigitta Vcelar
    • 4
  • Oscar McCook
    • 2
  • Peter Möller
    • 3
  • Michael Georgieff
    • 2
  • Enrico Calzia
    • 2
  • Peter Radermacher
    • 2
  • Hubert Schelzig
    • 1
  1. 1.Abteilung für Thorax- und GefässchirurgieUniversitätsklinikumUlmGermany
  2. 2.Sektion Anästhesiologische Pathophysiologie und Verfahrensentwicklung, Klinik für AnästhesiologieUniversitätsklinikumUlmGermany
  3. 3.Abteilung PathologieUniversitätsklinikumUlmGermany
  4. 4.Polymun Scientific GmbHViennaAustria

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