Effect of pre-treatment with catecholamines on cold preservation and ischemia/reperfusion-injury in rats.
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.
Gottmann
U
U
Fifth Department of Medicine (Nephrology/Endocrinology/Rheumatology), University Hospital Mannheim, University of Heidelberg, Mannheim, Germany. uwe.goettmann@med5.ma.uni-heidelberg.de
Brinkkoetter
P T
PT
Bechtler
M
M
Hoeger
S
S
Karle
C
C
Schaub
M
M
Schnuelle
P
P
Yard
B
B
van der Woude
F J
FJ
Braun
C
C
D000818:Animals; D002395:Catecholamines / Q000494:pharmacology*; D003080:Cold Temperature; D015925:Cryopreservation / Q000379:methods*; D004280:Dobutamine / Q000494:pharmacology; D004298:Dopamine / Q000494:pharmacology; D015259:Dopamine Agents / Q000494:pharmacology; D006085:Graft Survival; D019194:Ischemic Preconditioning / Q000379:methods*; D007668:Kidney / Q000187:drug effects / Q000502:physiology / Q000601:surgery; D016030:Kidney Transplantation; D008297:Male; D009392:Nephrectomy / Q000379:methods; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D011917:Rats, Inbred Lew; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000517:prevention & control; D013566:Sympathomimetics / Q000494:pharmacology
D002395:Catecholamines; D015259:Dopamine Agents; D013566:Sympathomimetics; D004280:Dobutamine; D004298:Dopamine; D009638:Norepinephrine