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01.09.2011 | Experimental

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

verfasst von: Florian Simon, Angelika Scheuerle, Michael Gröger, Brigitta Vcelar, Oscar McCook, Peter Möller, Michael Georgieff, Enrico Calzia, Peter Radermacher, Hubert Schelzig

Erschienen in: Intensive Care Medicine | Ausgabe 9/2011

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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.

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Titel: Comparison of carbamylated erythropoietin-FC fusion protein and recombinant human erythropoietin during porcine aortic balloon occlusion-induced spinal cord ischemia/reperfusion injury
verfasst von: Florian Simon
Angelika Scheuerle
Michael Gröger
Brigitta Vcelar
Oscar McCook
Peter Möller
Michael Georgieff
Enrico Calzia
Peter Radermacher
Hubert Schelzig
Publikationsdatum: 01.09.2011
Verlag: Springer-Verlag
Erschienen in: Intensive Care Medicine / Ausgabe 9/2011
Print ISSN: 0342-4642
Elektronische ISSN: 1432-1238
DOI: https://doi.org/10.1007/s00134-011-2303-4

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