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Effect of pre-treatment with catecholamines on cold preservation and ischemia/reperfusion-injury in rats.

Abstract
Treatment of organ donors with catecholamines reduces acute rejection episodes and improves long-term graft survival after renal transplantation. The aim of this study was to investigate the effect of catecholamine pre-treatment on ischemia/reperfusion (I/R)- and cold preservation injury in rat kidneys. I/R-injury was induced by clamping the left kidney vessels for 60 min along with a contralateral nephrectomy. Cold preservation injury was induced by storage of the kidneys for 24 h at +4 degrees Celsius in University of Wisconsin solution, followed by syngeneic transplantation. Rats were pre-treated with either dopamine (DA), dobutamine (DB), or norepinephrine (2, 5, and 10 microg/kg/min, each group) intravenously via an osmotic minipump for 24 h before I/R- and cold preservation injury. Pre-treatment with DA (2 or 5 microg/kg/min) and DB (5 microg/kg/min) improved recovery of renal function after I/R-injury and dose dependently reduced mononuclear and major histocompatibility complex class II-positive cells infiltrating the kidney after I/R-injury. One day after I/R-injury, upregulation of transforming growth factor (TGF)-beta 1 and 2 and phosphorylation of p42/p44 mitogen-activated protein kinases was observed in kidneys of animals treated with DA or DB. DA (5 microg/kg/min) and DB (5 microg/kg/min) pre-treatment reduced endothelial cell damage after 24 h of cold preservation. Only DA pre-treatment improved renal function and reduced renal inflammation after 24 h of cold preservation and syngeneic transplantation. Our results demonstrate a protective effect of pre-treatment with catecholamines on renal inflammation and function after I/R- or cold preservation injury. This could help to explain the potent organoprotective effects of catecholamine pre-treatment observed in human kidney transplantation.
AuthorsU Gottmann, P T Brinkkoetter, M Bechtler, S Hoeger, C Karle, M Schaub, P Schnuelle, B Yard, F J van der Woude, C Braun
JournalKidney international (Kidney Int) Vol. 70 Issue 2 Pg. 321-8 (Jul 2006) ISSN: 0085-2538 [Print] United States
PMID16760913 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Catecholamines
  • Dopamine Agents
  • Sympathomimetics
  • Dobutamine
  • Dopamine
  • Norepinephrine
Topics
  • Animals
  • Catecholamines (pharmacology)
  • Cold Temperature
  • Cryopreservation (methods)
  • Dobutamine (pharmacology)
  • Dopamine (pharmacology)
  • Dopamine Agents (pharmacology)
  • Graft Survival
  • Ischemic Preconditioning (methods)
  • Kidney (drug effects, physiology, surgery)
  • Kidney Transplantation
  • Male
  • Nephrectomy (methods)
  • Norepinephrine (pharmacology)
  • Rats
  • Rats, Inbred Lew
  • Reperfusion Injury (drug therapy, prevention & control)
  • Sympathomimetics (pharmacology)

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