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The effects of erythropoietin (EPO) and carbon monoxide (CO) on renal ischaemia/reperfusion (I/R) injury in an isolated porcine kidney model

By Atul Bagul


Kidney transplantation remains the best modality for renal replacement therapy, the key problem being lack of suitable organs for transplantation. Thus renewed interest in non-heart-beating-donor (NHBD) organs is on the increase to bridge this gap. NHBD organs are subjected to ischaemia-reperfusion (I/R) injury; the underlying pathophysiology, a complex inter-related sequence leading to short and long term renal allograft dysfunction. The aim of the study was to validate normothermic resuscitation perfusion (NP) as a preservation model followed by investigating the use of erythropoietin (EPO) and carbon-monoxide (CO). \ud Porcine kidneys were perfused with normothermic-autologus blood on an isolated-organ perfusion system (IOPS), design based on cardio-pulmonary bypass technology. Renal haemodynamics and functions were then measured during 3hr reperfusion. \ud NP restored renal blood flow and improved renal function, as assessed by % serum creatinine fall, area under curve (AUC) of serum creatinine. EPO when added to NP did not seem to add any major benefit other than marginally improve oxygen consumption. Carbon monoxide delivered as carbon monoxide-releasing molecule-3 (CORM-3) was able to improve urine output, renal blood flow, reduce intrarenal resistance as well as improve renal function reflected by significant improvement in AUC of creatinine clearance. \ud Normothermic resuscitation preservation not only reversed some of the deleterious effects of I/R injury, it also plays an important role as a versatile delivery system to assess various manipulatory agents that have potential in ameliorating I/R injury. This study provides further evidence that CO may be protective in renal perfusion injury and supports the use of low-dose CO releasing molecules as a method of CO delivery. Thus CORM-3 has the potential application in the field of NHBD kidney transplantation, which continues to be an expanding source of transplant kidneys. While EPO did not add any major benefits when used as a manipulating agent, may have its shortfall when applied to a NHBD kidney programme

Publisher: University of Leicester
Year: 2009
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  1. (2004). A comparison of renal preservation by cold storage and machine perfusion using a porcine autotransplant model. Transplantation
  2. (2002). A model of isolated autologously hemoperfused porcine slaughterhouse kidneys. Nephron.
  3. (1994). A new method for safe liver transplantation from non heart beating donors. In: Insitu liver oxygenation by cardiopulmonary bypass.[abstract]
  4. (1994). A novel site of erythropoietin production: oxygen-dependent production in cultured rat astrocytes.
  5. (1990). A prospective controlled trial of cold storage versus machine-perfusion preservation in cadaveric renal transplantation. Transplantation
  6. (2004). A report on the activity and clinical outcomes of renal non-heart beating donor transplantation in the United Kingdom. Clin Transplant.
  7. (2000). Acute renal failure II. Experimental models of acute renal failure: imperfect but indispensable.
  8. (2004). Acute renal hemodynamic effects of dimanganese decacarbonyl and cobalt protoporphyrin. Kidney Int.
  9. (1998). Adenovirus-mediated gene transfer into cold-preserved liver allografts: survival pattern and unresponsiveness following transduction with CTLA4Ig. Nat Med
  10. (2004). Administration of a CO releasing molecule at the time of reperfusion reduces infarct size in vivo. Am J Physiol Heart Circ Physiol.
  11. (2005). Administration of a CO-releasing molecule induces late preconditioning against myocardial infarction. J Mol Cell Cardiol.
  12. (1982). Advantage of cold storage over machine perfusion for preservation of cadaver kidneys. Transplantation
  13. (2001). Amelioration of post-ischaemic renal injury by contralateral uninephrectomy: A role of endothelin –1. Neprol Dial Transplant.
  14. (1983). An analysis of the optimal conditions for perfusing an isolated rabbit kidney with homologus blood. Renal Physiol.
  15. (1997). and long-term results with kidneys from non-heart-beating donors. Transplant Proc.
  16. (1996). Anti-erythropoietin receptor monoclonal antibody: epitope mapping, quantification of the soluble receptor, and detection of solubilized transmembrane receptor and the receptor expressing cells. Blood
  17. (2003). Antiapoptotic action of carbon monoxide on cultured vascular smooth muscle cells. Exp Biol Med.
  18. (1994). Antioxidant effectiveness in ischaemia-reperfusion tissue injury. Methods Enzymol.
  19. (2000). Apoptosis and caspase-3 in experimental anti-glomerular basement membrane nephritis. J Am Soc Nephrol.
  20. (2002). Apoptosis and inflammation in renal reperfusion injury. Transplantation
  21. (1996). Apoptosis in glomerular sclerosis. Kidney Int.
  22. (1998). Apoptosis in Ischaemia/reperfusion injury in human renal allografts. Transplantation
  23. (1996). Apoptosis in progressive cresentic glomerularnephritis. Lab Invest.
  24. (2001). Apoptosis versus necrosis during cold storage and rewarming of human renal proximal tubular cells. Transplantation,
  25. (2000). Auto oxidation of Glutathione in organ preservation solutions. Transplant Proc.
  26. (1997). Barbieux A Nifidipine improves recovery function of kidneys preserved in high sodium, low potassium cold storage solution: study with isolated perfused rat kidney technique. Nephrol Dial Transplant.
  27. (2002). Biliverdin reductase: a major physiological cytoprotectant. Proc Natl Acad Sci.
  28. (2003). Bioactivity and pharmacological actions of carbon monoxide releasing molecules. Curr Pharm Des.
  29. (2002). Bioengineering of recombinant human erythropoietin. In: Erythropoietin: Molecular Biology and Clinical Use,
  30. (2003). Bioflavoniods attenuate renal proximal tubular cell injury during cold preservation in Euro-collins and university of Wisconsin solutions. Kidney Int.
  31. (2002). Biological chemistry of carbon monoxide. Antioxid Redox Signal.
  32. (1998). Biology of erythropoietin. Haematologica
  33. (1998). Biology of erythropoietin. Haematologica.
  34. (2002). Cadaveric renal transplantation from non-heart-beating donors with graft survival for more than 10 years. Transplant Proc.
  35. (2001). Campbell m Recombinant human erythropoietin for chronic renal failure anaemia in pre-dialysis patients. Cochrane Database Syt Rev.
  36. (1999). Can we transplant a liver form an agonal non heart beating donor? (Evaluation of effectiveness of graft conditioning by an artificial heart and lung machine and drugs on graft injury). Organs and Tissue.
  37. (2004). Carbon monoxide activites K-Ca channels in newborn arteriole smooth muscle cells by increasing appernt Ca+ sensitivity of alpha subunits. Am J Physiol Heart Circ Physiol.
  38. (2002). Carbon monoxide and bile pigments: surprising mediators of vascular function. Vasc Med.
  39. (1997). Carbon monoxide controls the proliferation of hypoxic vascular smooth muscle cells.
  40. (1997). Carbon monoxide formation in ductus arteriosus in the lamb: implications for the regulation of muscle tone.
  41. (2000). Carbon monoxide generated by haeme oxygenas 1 supresses endothelial cell apoptosis. J Exp Med.
  42. (2001). Carbon monoxide generated by heme oxygenase-1 suppresses the rejection of mouse-to-rat cardiac transplants. J Immunol.
  43. (2004). Carbon monoxide headquarters.
  44. (1997). Carbon monoxide induced vasorelaxation and the underlying mechanisms.
  45. (2003). Carbon monoxide induces cytoprotection in rat orthotopic lung transplantion via anti-inflammatory and anti-apoptotic effects.
  46. (2003). Carbon monoxide inhalation protects rat intestinal grafts from ischaemi/reperfusion injury.
  47. Carbon monoxide inhibition of apoptosis during ischaemia-reperfusion lung injury is dependent on the p38 mitogen-
  48. Carbon monoxide inhibition of apoptosis during ischemia-reperfusion lung injury is dependent on the p38 mitogen-activated protein kinase pathway and involves caspase 3. The Journal of biological chemistry 2003; vol 278, no 2:
  49. (2004). Carbon monoxide inhibits endothelin-1 release by human pulmonary artery smooth muscle cells.
  50. (2002). Carbon monoxide inhibits human airway smooth muscle cell proliferation via mitogen activated protein kinase pathway. Am J Respir Cell Mol Biol.
  51. Carbon monoxide is a major contributor to the regulation of vascular tone in aortas expressing high levels of hemeoxygenase-
  52. (2002). Carbon monoxide modulates endotoxin-induced production of granulocyte macrophage colony stimulating factor in macrophages.
  53. (2003). Carbon monoxide modulates Fas/Fas ligand, caspases and Bcl-2 family proteins via the p38α mitogen-activated protein kinase pathway during ischaemic reperfusion lung injury.
  54. (2001). Carbon monoxide of vascular origin attenuates the sensitivity of renal arterial vessels to vasoconstrictors. J Clin Invest.
  55. (1999). Carbon monoxide poisoning. BMJ
  56. (2001). Carbon monoxide produced by isolated arterioles attenuates pressure-induced vasoconstriction. Am J Physiol heart Circ Physiol.
  57. (2008). Carbon monoxide protects against ischaemic-reperfusion injury in an experimental model of controlled nonheart-beating donor (NHBD) kidneys. Transplantation
  58. (2003). Carbon monoxide protects against liver failure through nitric oxide-induced heme oxygenase1. J Exp Med.
  59. (1999). Carbon monoxide provides protection against hyperoxic lung injury.
  60. (2002). Carbon monoxide releasing molecules: characterization of bio chemical and vascular activites. Circ Res.
  61. (2005). Carbon monoxide signaling in promoting angiogenesis in human microvessels endothelial cells. Antioxide Redox Signal.
  62. (1999). Carbon monoxide stimulates the apical -pS K+ channel of the rat ascending limb. J Clin Invest.
  63. (2003). Carbon monoxide suppresses arteriosclerotic lesion associated with chronic graft rejection and with ballon injury. Nat Med.
  64. (2005). Carbon monoxide-releasing molecules (CO-RM) attenuate the inflammatory response elicited by lipopolysaccharide in RAW264.7 murine macrophages.
  65. (1993). Carbon monoxide: a putative neural messenger. Science
  66. (2002). Carbon monoxide: innovative anti-inflammatory properties of an age-old gas molecule. Antioxid Redox Signal.
  67. (2004). Carbon monoxide: to boldly go where NO has gone before. Sci STKE.
  68. (2004). Carbonmonoxide in bilogy and medicine. Bioassays
  69. (2003). Carbonmonoxide- a new gaseous modulator of gene expression. ActaBiochim Pol.
  70. (2001). Cardiac-specific expression of heme oxygenase-1 protects against ischaemia and reperfusion in transgenic mice. Circ Res.
  71. (2003). Cardioprotective actions by a water soluble carbon monoxide releasing molecule. Circ Res.
  72. (1999). Caspase inhibitors in prevention of apoptosis.
  73. (2000). Caspase-12 mediates endoplasmicreticulum-specific apoptosis and cytotoxicity by amyloid-beta. Nature
  74. (1998). Caspases: Enemies within. Science
  75. (1996). Catalytic metal ions and the loss of reduced glutathione from University of Wisconsin preservation solution. Transplantation
  76. (1996). Cell apoptosis and proliferation in experimental chronic obstructive uropathy. Kidney Int.
  77. (1993). Cellular mechanism of acute ischaemia injury in the kidney. Annu Rev Med
  78. (1997). Changes in adenine nucleotides and lipid hydroperoxides during normothermic cardiopulmonarybypass in a porcine model of type II non heart beating donors. Transpl Proc.
  79. (2000). Chronic allograft nephropathy-a model of impaired repair from injury? Nephrol Dial Transplant.
  80. (2001). Chronic rejection. Immunity
  81. (1985). Cloning and expression of the human erythropoietin gene. Proc Natl Acad Sci.
  82. (2002). Coffee creamer, the bionic man and organ transplantation. Surgery
  83. (2004). Cold ischaemic injury of transplanted kidney: new insights from experienced studies.
  84. (2006). Comparison of cold storage versus hypothermic machine perfusion in a preclinical model of liver transplantation. Transplantation 2006; 82(1): 112 (Abstract presented WTC
  85. (2005). Comparison of renal allograft fibrosis after transplantation from heart-beating and non-heart-beating donors.
  86. CORM-A1: a new pharmacologically active carbon monoxide –releasing molecule.
  87. (2004). Cytoprotection by darbepoetin/epoetin alfa in pig tubular and mouse mesangial cells. Kidney Int.
  88. (2002). De Campos SB Mycophenolate mofetil attenuates renal ischaemic/reperfusion injury.
  89. (1998). Decreasing the cold ischaemia time. Transpl Proc.
  90. (2006). Delayed administration of darbepoetin or erythropoietin protects against ischaemic acute renal injury and failure. Kidney Int.
  91. (2003). Delayed graft function after renal transplantation from a non-heart- beating donors. Transplant
  92. Delayed graft function in kidney transplantation. Lancet 2004; vol 364, no 9447:
  93. (1993). Delayed graft function is associated with an increased incidence of occult rejection and results in poorer graft survival. Transplant Proc.
  94. (1995). Delayed graft function, acute rejection and outcome after renal transplantation. Transplantation
  95. (1998). Deleterious effects of delayed graft function in cadaveric renal transplant recipients independent of acute rejections. Transplantation
  96. (2001). Deleterious effects of prolonged cold ischaemia on renal function. Transplant Int.
  97. (2004). Derivatives of erythropoietin that are tissue protective but not erythropoietic. Science
  98. (1969). Development of an isolated perfused dog kidney with improved function.
  99. (2002). Different patterns of renal cell killing after warm and cold ischaemia. Renal Fail.
  100. (2004). Dipyridamole protects the liver against warm ischemia and reperfusion injury. J Am Coll Surg.
  101. (2000). Dynamics of haemoxygenase-1 expression and bilirubin production in cellular protection against oxidative stress.
  102. (1999). Early kidney TNF-alpha expression mediates neutrophil infiltration and injury after renal ischemia-reperfusion. Am J physiol.
  103. Effect of a 21-aminosteroid, U74006F, on lipid peroxidation and glomerulotubular function following experimental renal ischemia.
  104. (2006). Effects of arterial pressure in an experimental isolated haemoperfused porcine kidney preservation System. Br
  105. (2005). Effects of carbon monoxide releasing molecules on porcine endothelial cells and primate PBMC.
  106. (2003). Effects of caspase inhibition on the progression of experimental glomerulonephritis. Kidney Int.
  107. (2008). Effects of erythropoietin on ischaemia/reperfusion injury in a controlled non-heart beating donor kidney model. Transpl Int.
  108. (2001). Effects of hypothermic machine perfusion on rat liver function depending upon the route of perfusion. Transplantation
  109. (1951). Endogenous formation of carbon monoxide: the CO concentration in the inspired and expired air of hospital patients. Acta Physiol Scand.
  110. (2005). Erythroietin protects the myocardium against reperfusion injury in vitro and in vivo. Basic Res Cardiol.
  111. (2006). Erythropietin administered protects against functional impairment and cell death after ischaemic renal injury in pigs. BJU Int.
  112. (2006). Erythropietin attenuates renal injury in experimental acute renal failure ischaemic/reperfusion model. Nephrol Dial Transplant.
  113. (2001). Erythropoietin acts as a trophic factor in neonatal rat intestine. Gut
  114. (2002). Erythropoietin administration protects retinal neurons from acute ischemia-reperfusion injury. Proc Natl Acad Sci.
  115. (2005). Erythropoietin and myocardial protection: What's new? Fundam Clin Pharmacol.
  116. (2004). Erythropoietin attenuates the tissue injury associated with hemorrhagic shock and myocardial ischemia. Shock
  117. (2001). Erythropoietin expression in primary rat Sertoli and peritubular myoid cells. Blood
  118. (2002). Erythropoietin in human milk: physiology and role in infant health. J Hum Lact.
  119. (2004). Erythropoietin on a tightrope: Balancing neuronal and vascular protection between intrinsic and extrinsic pathways. Neurosignals
  120. (2004). Erythropoietin protects against ischaemic acute renal injury.
  121. (2004). Erythropoietin protects against ischaemic acute renal injury. Nephrol Dial Transplant.
  122. (2004). Erythropoietin protects the kidney against injury and dysfunction caused by ischaemia-reperfusion.
  123. (1999). Erythropoietin reduces the development of experimental, inflammatory bowel disease. J Pharmacol.
  124. (2001). Erythropoietin regulates the in vitro and in vivo production of neuronal progenitors by mammalian forebrain neural stem cells.
  125. (1990). Erythropoietin retards DNA breakdown and prevents programmed death in erythroid progenitor cells. Science
  126. (2000). Erythropoietin stimulates proliferation of human renal carcinoma cells. Kidney Int.
  127. (1994). Erythropoietin stimulates testosterone production in man.
  128. (2002). Erythropoietin therapy for acute stroke is both safe and beneficial. Mol Med.
  129. (2001). Erythropoietin-mediated neuroprotection involves cross-talk between Jak2 and NF-kappaB signalling cascades. Nature
  130. (2004). Erythropoietin: Is it more than correcting anaemia? Nephrol Dial Transplant.
  131. (1992). Erythropoietin: Structure, control of production, and function. Physiol Rev.
  132. (1994). Erythropoietin: the promise and the facts. Kidney Int.
  133. (1997). Erytropoietin receptor is expressed in rat hippocampal and cerebral cortical neurons and erythropoietin prevents in vitro glutamate-induced neuronal death. NeuroScience
  134. (1998). Estrogendependent production of erythropoietin in uterus and its implication in uterine angiogenesis.
  135. (1991). Does Carbon monoxide have a physiological function? Trends Phrmacol Sci.
  136. (1992). Evidence for specific binding and stimulatory effects of recombinant human erythropoietin on isolated adult rat Leydig cells. Acta Endocrinol. (Copenh)
  137. (1998). Ex vivo gene therapy prevents chronic graft vascular disease in cardiac allografts. J Thorac Cardiovasc Surg.
  138. (2002). ex-vivo exposure to carbon monoxide prevents hepatic ischaemic/reperfusion injury through p38MAP Kinase Pathway. Hepatology
  139. (1994). Experimental evaluation of celsior, a new heart preservation solution. Eur J Cardiothorac Surg.
  140. (2008). Experimental renal preservation by normothermic resuscitation perfusion with autologous blood.
  141. (2000). Expression and action of heme oxygenase in the renal medulla of rats. Hypertension
  142. (2002). Extended preservation of non-heart-beating donor livers with normothermic machine perfusion.
  143. (1988). Factors influencing early renal function in cadaver kidney transplants. A case-control study. Transplantation
  144. (1998). Fas ligand gene transfer to renal allografts in rats: effects on allograft survival. Transplantation
  145. (1992). Feedback modulation of renal and hepatic erythropoietin mRNA in response to graded anemia and hypoxia.
  146. (1996). Fernández-Luna JL: Erythropoietin can promote erythroid progenitor survival by repressing apoptosis through bcl-XL and bcl-2. Blood
  147. Ferritin: acytoprotective antioxidant stratagem of endothelium.
  148. (2002). Functional recovery of preserved livers following warm ischaemia: Improvement by machine perfusion preservation. Transplantation
  149. (2003). Gene therapy expressing amino-terminal truncated monocyte chemoattractant protein-1 prevents renal ischemia-reperfusion injury. J Am Soc Nephro.
  150. (2005). Gene transfer of heat-shock protein 20 protects against ischemia /reperfusion injury in rat hearts. Acta pharmacologica Sinica
  151. (2002). Gene transfer of heme oxygenase-1 and carbon monoxide delivery inhibit chronic rejection.
  152. (1997). Gracia Valdecasas JC, Lopez Boado MA Adenine nucleotide liver tissue concentrations fromnon heart beating donor pigs and organs viability after liver transplantation. Transpl Proc.
  153. (2003). GW274150, a potent and highly selective inhibitor of iNOS, reduces experimental renal ischaemia reperfusion injury. Kidney Int.
  154. (1906). Haemopoietic activity of the serum in blood regeneration.
  155. (1998). Haemoxygenase1-derived carbon monoxide contributes to the suppression of acute hypertensive responses in vivo. Circ Res.
  156. (2003). Hematopoietic stem cells contribute to regeneration of renal tubules after renal ischemia-reperfusion injury in mice.
  157. (2003). Heme oxygenase is expressed in human pulmonary artery smooth muscles where carbon monoxide has an antiproliferative role.
  158. (2003). Heme oxygenase-1 : unleashing the protective properties of heme. Trends Immunol.
  159. (2004). Heme oxygenase-1 dervied carbon monoxide protects hearts from transplant associated ischaemia-reperfusion injury.
  160. (2000). Hemeoxygenase-1 derived bilirubin ameliorates post ischaemic myocardial dysfunction. Am J Physiol Heart Cir Phyiology.
  161. (2004). Hemeoxygenase-1 inhibition of Map Kinases, calcineurin/NF AT signalling and hypertrophy in cardiac myocytes. Cardiovasc Res.
  162. (2001). Hemeoxygenase-1 protects against vascular constriction and proliferation. Nat Med.
  163. (2002). Hemeoxygenase-1: the emerging molecule has arrived.
  164. (2000). Hemeoxygenase: colors of defense against cellular stress.
  165. Hemodynamic studies on normothermic perfusion of the isolated pig
  166. (1998). Hepatic blood flow and oxygen extraction ratio during normothermic recirculation and total body cooling as viability predictors in non heart beating donor pigs. Transplantation
  167. (1998). Hepatic preconditioning in rats is defined by a balance of adenosine and xanthine. Hepatology
  168. (2000). Hepatic preconditioning preserves energy metabolism during sustained ischaemia. Am J Pysiol Gastrointes Liver Physiol.
  169. (2005). Heurn LW. Outcome of non-heart-beating donor kidneys with prolonged graft function after transplantation.
  170. (2002). HIF-1-induced erythropoietin in the hypoxic retina protects against light-induced retinal degeneration. Nat Med.
  171. (1999). Human recombinant erythropoietin inhibits interleukin-1beta-stimulated nitric oxide and cyclic guanosine monophosphate production in cultured rat vascular smooth-muscle cells. Nephrol Dial Transplant.
  172. (1995). Hydroxyl radical production in the brain after CO hypoxia in rats. Free Radic Biol Med.
  173. (2004). Hyperosmolar solution effects in guinea pig airways. III studies on identity of epithelium derived relaxing factor in isolated perfused trachea using pharmacological agents. J Pharmcol Exp Ther.
  174. (1998). Hypothermic oscillating liver perfusion stimulates ATP synthesis prior to transplantation. J Surg Res.
  175. (1997). Immunohistochemical analysis of in vivo patterns of expression of CPP32(caspase-3), a cell death protease. Cancer Res.
  176. (1994). Increased incidence of rejection in patients with delayed graft function. Clin Transplant.
  177. (1998). Induction of apoptosis in ischaemic-reperfusion model of mouse kidney: possible involvement of Fas.
  178. (2003). Induction of heme oxygenase-1 expression in murine macrophages is essential for the anti-inflammatory effects of low dose 15 deoxydelta 12, 14-prostaglandin J2. J Bio Chem.
  179. (2003). Induction of heme oxygenase-1 in kidneys during ex vivo warm perfusion. Transplantation,
  180. (2002). Inhibition of inducible nitric oxide synthase reduces renal ischemia /reperfusion injury. Kidney Int.
  181. Inhibition of intercellular adhesion molecule-1 with antisense deoxynucleotides prolongs renal isograft survival in the rat. Kidney international 1998; vol 54, no 6:
  182. (1987). Inhibition of platelate aggregation by carbon monoxide is mediated by activation of guanylate cyclase. Mol Pharmacol.
  183. (2004). injury to the liver in mice. Surgery
  184. (2002). Interleukin-8 release during early reperfusion predicts graft function in human lung transplantation. Am J Respir Crit Care Med.
  185. (1989). Intermediate Normothermic perfusion during cold storage of ischaemically injured kidneys. Transpl Proc.
  186. (2003). Is Ischaemic preconditioning of kidney clinically relevant? Surgery
  187. (1995). Ischemic acute tubular necrosis induces an extensive local cytokine response. Evidence for induction of interferongamma, transforming growth factor-beta 1, granulocyte-macrophage colonystimulating factor, interleukin-2, and interleukin-10. Transplantation
  188. Isolation and characterization of genomic and cDNA clones of human erythropoietin.
  189. Isolation of human erythropoietin with monoclonal antibodies.
  190. (2005). Jurisch A Introduction of carbon monoxide in the donor reduces graft immunogenicity and chronic graft deterioration. Transplant Proc.
  191. (1992). Kidney preservation ex vivo for transplantation. Annu Rev Med.
  192. (1992). Late graft loss in cadaveric renal transplantation. Transplant
  193. (2006). Leucoycte depletion improves renal function during reperfusion using an experimental isolated haemoperfused organ preservation system.
  194. (1990). Leukocyte adhesion to endothelium in inflammation. Cell
  195. (1998). Liver conditioning after cardiac arrest: the use of normothermic reciculation in an experimental animal model. Transpl Int.
  196. (2001). Liver transplantation after organ preversation with normothermic extracorporeal perfusion. Ann Surg.
  197. (1995). Lodish HF: Generation of committed erythroid BFU-E and CFU-E progenitors does not require erythropoietin or the erythropoietin receptor. Cell
  198. (2002). Long-term outcome of tacrolimus in cadaveric kidney transplantation from non-heart-beating donors. Transplant Proc.
  199. (1998). Long-term renal function in on-heartbeating donor kidney transplantation: a single-center experience. Transplantation
  200. (1990). Malondialdehyde determination as index of lipid peroxidation. Methods Enzymol.
  201. (1991). Marzi I rinse solution: a new strategy to increase survival time after orthotopic liver transplantation in the rat. Tranplantation
  202. (1987). McDonagh AF Bilirubin is an antioxidant of possible physiological importance. Science
  203. (1987). Mechanism of action of ex vivo blood rescue in six day preserved kidneys. Transpl Proc.
  204. (2004). Mechanism of internal anal sphincter relaxation by CORM-1, Attentic CO and NANC nerve stimulation.
  205. (2000). Mechanism of reduced GFR in rabbits with ischaemic acute renal failure. Ren Fail.
  206. (2002). Mechanisms of caspase activation and inhibition during apoptosis. Mol Cell.
  207. (1995). Mechanisms of filtration failure during post ischaemic injury of the human kidney. A study of reperfused renal allograft. J Clin Invest.
  208. (1999). Mesangial cell apoptosis: the major mechanism for resolution of glomerular hypercellularity in experimental mesangial proliferative nephritis. J Clin Invest.
  209. (2003). Metal carbonyls: a new class of Pharmaceuticals? Angew Chem Int Ed Engl.
  210. (1969). Microsomal heme oxygenase: characterization of the enzyme.
  211. (1992). Microvascular ischemia-reperfusion injury in striated muscle: significance of no reflow.
  212. (1986). Mitochondrial oxygenation of carbon monoxide.
  213. (2002). Mitochondrial respirotary chain as a new target for anti- ischaemic molecules.
  214. (1988). MJ: Localization of erythropoietin synthetizing cells in murine kidneys by in situ hybridization. Blood
  215. (2004). Molecular biology of erythropietin. Intern med.
  216. (2005). Motterlini r. mitochondrial respiratory chain and NADPH oxidase are targerts for the antiproliferative effects of carbon monoxide in human airway smooth muscle. J Bio Chem.
  217. (1999). neuritrophic and angiogenic functions of erythropoietin and regulation of erythropoietin production.
  218. (2000). Neurons overexpressing heme oxygenase-1 resist oxidative stress – mediated cell death.
  219. (2001). Neutralization of Gro alpha and macrophage inflammatory protein-2 attenuates renal ischemia/reperfusion injury.
  220. (2002). NF-kappaB plays a key role in hypoxiainducible factor-1-regulated erythropoietin gene expression. Exp Hematol.
  221. (1993). Nitric oxide mediates renal vasodilation during erythropoietin-induced polycythemia. Kidney Int.
  222. (2002). Non-heart-beating donors under extracorporeal membrane oxygenation support. Transplant Proc.
  223. (1996). Nonheart-beating donor program contributes 40% of kidneys for transplantation. Transplant Proc.
  224. (1998). Normothermic Blood Perfusion of Isolated Kidneys: I. In Vitro evaluation of renal function.
  225. (2000). Normothermic Blood Perfusion of Isolated Kidneys: II. In Vitro evaluation of renal function followed by orthotopic transplantation. ASAIO
  226. (2002). Normothermic blood perfusion of isolated rabbit Kidneys. Transpl Int.
  227. (2000). Normothermic recirculation reduces primary graft dysfunction of kidneys obtained from non-heart beating donors. Transpl Int.
  228. (2006). Novel renoprotective actions of erythropoietin: New uses for an old harmone. Nephrology
  229. (2004). Ohno m, Ayabe S Carbonmonoxide protects against cardiac ischaemia reperfusion injury in vivo via MAPK and Akt-eNOS pathways. Arterioscler thromb Vasc Bio.l
  230. Outcome of transplantation of non-heart-beating donor kidneys. Lancet 1995; vol 346, no 8966: p 53
  231. (2003). Outcome of transplantation using kidneys from controlled (Maastricht category 3) non-heart-beating donors. Clin Ttransplant.
  232. (1999). Overexpression of heme-oxygenase-1 is neuroprotective in a model of permanent middle cerebral artery occlusion in transgenic mice.
  233. (1985). Oxygen free radical induced damage in kidneys subjected to warm ischemia and reperfusion. Protective effect of superoxide dismutase. Ann Surg.
  234. (1987). Oxygen-derived radicals a link between reperfusion injury and inflammation. Fed Proc.
  235. (2003). oxygenated machine perfusion mitigates surface antigen expression and improves preservation of predamaged donor livers. Cryobiology
  236. (2001). Paradoxical rescue from ischemic lung injury by inhaled carbon monoxide driven by depression of fibrinolysis. Nat Med.
  237. (1996). Physiological and histological characterisation of pig kidney in vitro perfusion model for xenotransplantation studies.
  238. (2001). Pleiotropic functions and tissue-specific expression of erythropoietin. News Physiol Sci.
  239. (2003). Pleiotropic functions of erythropoietin. Intern Med.
  240. Plzak L: Role of the kidney in erythropoiesis.
  241. (2001). Positive effect of the induction of p21WAF1/CIP1 on the course of ischaemic acute renal failure. Kidney Int.
  242. (1989). Postischemic renal injury is mediated by neutrophils and leukotrienes. Am J physio.
  243. (2004). Pre-treatment with EPO reduces the injury and dysfunction caused by ischaemia/reperfusion in the mouse kidney in vivo. Kidney Int.
  244. (1986). Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. Circulation
  245. (1997). Predictors of graft outcome in warm ischemically damaged organs. Transplant Proc.
  246. (1983). Preservation of cadaveric kidneys. Cold storage or machine perfusion? Arch Surg.
  247. (2004). Preservation of porcine Non-Heart beating donor livers by sequential cold storage and warm perfusion. Transplantation
  248. (1999). Prolongation of cardiac allograft survival with intracoronary viral interleukin-10 gene transfer. Transplant Proc.
  249. (2005). Prolonged warm ischaemic times lead to significant impairment of early graft function during perfusion on an isolated haemoperfused porcine kidney model. Abstract published,
  250. (1998). Prolonged warm ischemia affects longterm prognosis of kidney transplant allografts from non-heart-beating donors. Transplant Proc.
  251. (2002). Propionyl-L-carnitine prevents renal function deterioration due to ischemia/reperfusion. Kidney Int.
  252. (2005). Protection against ischaemia/reperfusion injury in cardiac and renal transplantation with CO,
  253. (2004). Protection of transplant- induced renal ischaemia-reperfusion injury with carbon monoxide. Am J physiol renal physiol.
  254. (2005). Protective effect of carbon monoxide-releasing compounds in ischaemic-induced acute renal failure. J Am Soc Nephrol.
  255. (2005). Protective effect of erythropoietin on renal ischemia and reperfusion injury.
  256. (1998). Protective effect of FK409, a spontaneous nitric oxide releaser, on ischemic acute renal failure in rats. J Pharmacol exp Ther.
  257. (2000). Protective effect of heme oxygenase induction in ischaemic acute renal failure. Crit Care Med.
  258. (2003). Protective effect of Nacetylcysteine on renal ischemia/reperfusion injury in the rat.
  259. (2003). Protective effects of carbonmonoxide inhalation for cold preserved small intestinal grafts. Surgery
  260. (1999). Protective effects of celsior in lung transplantation. J Heart Lung Transplant.
  261. (2004). Protective effects of exogenous bilirubin on ischaemia-reperfusion injury in the isolated perfused rat kidney. Am J Physiol Renal Physiol.
  262. (2004). Protective role of hemeoxygenase-1 in renal ischaemia. Antioxid Redox Signal.
  263. (2006). Pulsatile-machine preservation versus cold storage in mate renal allografts. Transplantation 2006; 82(1): 112 (Abstract presented WTC
  264. (1977). Purification of human erythropoietin.
  265. (1999). rat and mouse kidney express functional erythropoietin receptors. Kidney Int.
  266. (2002). Recombinant human erythropoietin counteracts secondary injury and markedly enhances neurological recovery from experimental spinal cord trauma. Proc Natl Acad Sci.
  267. (2006). Recombinant human erytropoietin protects the liver from hepatic ischemiareperfusion injury in the rat. Transpl Int.
  268. (2001). Reduced vasorelaxant effect of carbon monoxide in diabetes and the underlying mechanisms. Diabetes
  269. (2001). Reduction of severe ischemia/reperfusion injury in rat kidney grafts by a soluble P-selectin glycoprotein ligand. Transplantation
  270. (1995). Regional renal blood flow in normal and diseased states. Urol Res.
  271. (1999). Regulation of glomerular cell number by apoptosis. Kidney Int.
  272. (1996). Renal ischaemia-reperfusion Injury. Br
  273. (1980). Renal preservation prior to transplantation. Transplantation
  274. (2005). Renal transplantation from non-heart beating donors: a single center 10 year experience. Transplant Proc.
  275. (2006). Rescue of the cold preserved rat liver by hypothermic oxygenated machine perfusion.
  276. (2000). Retinoic acid stimulates erythropoietin gene transcription in embryonal carcinoma cells through the direct repeat of a steroid/thyroid hormonereceptor response element half-site in the hypoxia-response enhancer. Blood
  277. (1994). Role of calcium in reperfusion injury in kidney.
  278. (1997). Role of carbon monoxide in central regulation of arterial pressure. Hypertension
  279. (2004). Role of cGMP in carbon monoxide induced cerebral vasodilatation in piglets. Am J Physiol Heart Circ Physiol.
  280. (1995). Role of prostaglandins and nitric oxide in mediating renal response to volume expansion.
  281. (1997). Ruthenium complexes as nitric oxide scavengers: a potential therapeutic approach to nitric oxide mediated diseases.
  282. (2004). Sampaio FJ. Pig kidney: anatomical relationships between the intra-renal arteries and kidney collecting system. Applied study for urological research and surgical
  283. (1989). SE: Quantitation of erythropoietin-producing cells in kidneys of mice by in situ hybridization. Correlation with hematocrit, renal erythropoietin mRNA, and serum erythropoietin concentration. Blood
  284. Selectin inhibitor bimosiamose prolongs survival of kidney allografts by reduction in intragraft production of cytokines and chemokines.
  285. (2003). Sfacteria A et al. Asialoerythropoietin is a nonerythropoietic cytokine with broad neuroprotective activity in vivo.
  286. (2004). Small interfering RNA targeting Fas Protects mice against renal ischaemia-reperfusion injury.
  287. (2002). Soares MP Carbon monoxide protects pancreatic beta-cells from apoptosis and improves islet function/survival after transplantation. Diabetes
  288. (1985). Soyabean trypsin inhibitor attenuates ischaemic injury to the feline small intestine. Gastroenterology
  289. (2002). Studies on the development of carbon monoxide releasing molecules: potential applications for the treatment of cardiovascular dysfunction. Wang R,ed. Carbon monoxide and cardiovascular function. Boca Raton, Fla: CRC ;
  290. (1992). Study of the actions of human recombinant erythropoietin on rat renal haemodynamics. Clin Sci. (Lond)
  291. (2003). Survival transplantation of preserved non heart beating donor rat livers: Preservation by hypothermic machine perfusion. Transplantation
  292. (1988). Tambourin P: Peritubular cells are the site of erythropoietin synthesis in the murine hypoxic kidneys. J Clin Invest.
  293. (2001). targeted expression of heme oxygenase-1 prevents pulmonary inflammatory and vascular responses to hypoxia. Proc Natl Acad Sci.
  294. (2001). Taura P Hepatic xanthine levels as viability predictor of Livers procured from non-heart beating donor pigs. Transplantation
  295. (1994). The beneficial effect of human recombinant superoxide dismutase on acute and chronic rejection events in recipients of cadaveric renal transplants. Transplantation
  296. (1997). The caspase Family of Cysteine proteases.
  297. (2003). The clinical toxicology of carbon monoxide. Toxicology.
  298. The cytokineadhesion molecule cascade in ischemia/reperfusion injury of the rat kidney.
  299. (2005). The effect of Normothermic recirculation is mediated by ischaemic preconditioning in NHBD Liver Transplantation. Am
  300. (2002). The effects of endothelin antagonist on renal ischaemia-reperfusion injury and the development of acute renal failure in the rat. Nephrol Dial Transplant.
  301. (2004). The erythropoietin receptor and its expression in tumor cells and other tissues. Oncologist
  302. The ferritins: molecular properties, iron storage function cellular regulation. Biochimica et biophysica acta1996; vol 1275, no 3:
  303. (1997). The haemoxygenase system: a regulator of second messenger gases. Annu Rev Pharmacol Toxicol.
  304. (1991). The high cost of delayed graft function in cadaveric renal transplantation. Transplantation
  305. (1987). The importance of prolonged post transplant dialysis requirement in cyclosporine treated renal allograft recipients. Clin Transplant.
  306. (1998). The molecular and cellular basis of reperfusion injury following organ transplantation. Transplant Rev.
  307. (2004). The permissive role of endothelial NO in CO –induced cerebrovascular dilatation. Am J Physiol Heart Circ Physiol.
  308. (2002). The phosphoinositide 3-kinase pathway. Science
  309. (1993). The possibility of resuscitating livers after warm ischaemic injury. Transplantation
  310. (2003). The role of chemokines and chemokine receptors in alloantigenindependent and alloantigen-dependent transplantation injury. Seminars in Immunology
  311. (2000). The trouble with kidneys derived from the non heartbeating donor: a single center 10-year experience. Transplantation
  312. (2001). Therapeutic administration of an endothelin-A receptor antagonist after acute ischaemic renal failure dose-dependently improves recovery of renal function. J Cardiovasc Pharamcol.
  313. (2005). therapeutic applications of carbon monoxide releasing molecules. Expt Opin Investig Drugs.
  314. (1996). Thirty-two years of renal transplantation in Zurich. Clinical Transplant.
  315. (2000). Tissuespecific regulation of erythropoietin production in the murine kidney, brain, and uterus. Am J Physiol Endocrinol Metab.
  316. (2002). Total body cooling using cardiopulmonary bypass for procurement from non-heart-beating donors. Transplant Proc.
  317. (2002). Transfection and transgene expression in a human kidney during ex vivo warm perfusion. Transplant Proc.
  318. (1998). Transplantation of kidneys from donors whose hearts have stopped beating.
  319. (1996). Transplantation of kidneys harvested from non-heart-beating donors: early and long-term results. Transpl Int.
  320. (2006). Treatment with CO-RMs during cold storage improves renal function at reperfusion. Kidney Int.
  321. (1989). Treatment with tin prevents the development of hypertension in spontaneously hypertensive rats. Science
  322. (1998). Trimetazidine reverses deleterious effects of ischemia-reperfusion in the isolated perfused pig kidney model.
  323. (2005). Tsung A Carbonmonoxide inhalation ameliorates cold ischaemia/reperfusion injury after rat liver transplantation. Surgery
  324. (1987). Ullrich v. Inhibition of platelet aggregation by carbon monoxide is mediated by activation of guanylate cyclase. Mol Pharmacol.
  325. (2005). Ultraviolet A (320-400 nm) modulation of ultraviolet B (290-320) induced immune suppression is mediated by carbon monoxide. J Invest Dermatol.
  326. (1999). Upregulation of hemeoxygenase-1 protects genetically fat zucker rat livers from ischaemia/reperfusion injury. J Clin Invest.
  327. (2005). Use of different immunosuppressive strategies in recipients of kidneys from non-heart-beating donors. Transpl Int.
  328. (1997). Use of erythropoietin outside the setting of uremia. Blood
  329. (2002). Usefulness of continuous hypothermic perfusion preservation in renal transplantation from non-heart-beating donors. Transplant Proc.
  330. (2000). Varbon monoxide has anti-inflammatory effects involving the mitogen –activated protein kinase pathway. Nat Med.
  331. Vasoactive properties of CORM-3, a novel water soluble carbon monoxide releasing molecule.
  332. (2001). Vasoregulatory function of the heme-heme oxygenase-carbon monoxide system.
  333. (1989). Viability assays for preversed cells, tissues and organs. Cryobiology
  334. (1989). Viability assays in organ preservation. Cryobiology
  335. (1991). WD: Erythropoietin is both a mitogen and a survival factor. Blood
  336. (2004). Wooodruff TM The role of the complement system in ischaemia-reperfusion injury. Shock
  337. (2003). Yaruz A Prevention of renal damage by alpha tocopherol in ischemia and reperfusion models of rats. Urol Res.
  338. (1999). Zhang F Contribution of endogenous carbon monoxide to regulation of diameter in resistance vessels.
  339. (1990). Zon LI: Erythropoietin receptor. Subunit structure and activation.

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