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.
PURPOSE: Recombinant humanerythropoietin (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.
Authors: Jeroen Lips; Peter de Haan; Gert Joan Bouma; Rebecca Holman; Eric van Dongen; Cor J Kalkman Journal: Anesthesiology Date: 2005-02 Impact factor: 7.892
Authors: Michael Brines; Giovanni Grasso; Fabio Fiordaliso; Alessandra Sfacteria; Pietro Ghezzi; Maddalena Fratelli; Roberto Latini; Qiao-Wen Xie; John Smart; Chiao-Ju Su-Rick; Eileen Pobre; Deborah Diaz; Daniel Gomez; Carla Hand; Thomas Coleman; Anthony Cerami Journal: Proc Natl Acad Sci U S A Date: 2004-09-29 Impact factor: 11.205
Authors: Marek Nalos; Pierre Asfar; Carole Ichai; Peter Radermacher; Xavier Maurice Leverve; Gebhard Fröba Journal: Intensive Care Med Date: 2002-11-02 Impact factor: 17.440
Authors: Šárka Matějková; Angelika Scheuerle; Florian Wagner; Oscar McCook; José Matallo; Michael Gröger; Andrea Seifritz; Bettina Stahl; Brigitta Vcelar; Enrico Calzia; Michael Georgieff; Peter Möller; Hubert Schelzig; Peter Radermacher; Florian Simon Journal: Intensive Care Med Date: 2013-01-05 Impact factor: 17.440
Authors: Oscar McCook; Michael Georgieff; Angelika Scheuerle; Peter Möller; Christoph Thiemermann; Peter Radermacher Journal: Crit Care Date: 2012-09-26 Impact factor: 9.097
Authors: Massimo Antonelli; Marc Bonten; Jean Chastre; Giuseppe Citerio; Giorgio Conti; J Randall Curtis; Daniel De Backer; Goran Hedenstierna; Michael Joannidis; Duncan Macrae; Jordi Mancebo; Salvatore M Maggiore; Alexandre Mebazaa; Jean-Charles Preiser; Patricia Rocco; Jean-François Timsit; Jan Wernerman; Haibo Zhang Journal: Intensive Care Med Date: 2012-01-04 Impact factor: 17.440