Long-term renal preservation and prevention of acute tubular necrosis by inhibition of arachidonate metabolism.
Experimental preservation time for pulsatile perfused dog kidneys was extended from three to five days by phospholipase A2 inhibition suggesting a pathomechanical role of products of phospholipolysis like thromboxane and leukotrienes in the development of acute graft failure after renal transplantation. We therefore investigated the effects of thromboxane- and leukotriene synthase inhibitors on postoperative renal transplant function in a model of pulsatile perfusion preservation as well as a cold storage preservation of dog kidneys. Addition of a thromboxane-synthase-inhibitor to the perfusion medium in pulsatile perfused kidneys and the combined application of a thromboxane-synthase-inhibitor and a leukotriene-synthase-inhibitor to the recipient of a cold storage preserved graft, improved graft function and reduced the incidence of delayed graft function as well as histopathological features of acute tubular necrosis.
Schilling
M
M
Departement für Viszerale- und Transplantationschirurgie, Universität, Bern, Inselspital.
Saunder
A
A
Southard
J H
JH
Belzer
F O
FO
D000241:Adenosine; D000493:Allopurinol; D000818:Animals; D016718:Arachidonic Acid / Q000037:antagonists & inhibitors* / Q000378:metabolism; D001241:Aspirin / Q000494:pharmacology; D001572:Benzofurans / Q000494:pharmacology; D004285:Dogs; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D005978:Glutathione; D007052:Ibuprofen / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D007328:Insulin; D016030:Kidney Transplantation / Q000379:methods*; D007683:Kidney Tubular Necrosis, Acute / Q000473:pathology / Q000517:prevention & control*; D007684:Kidney Tubules / Q000473:pathology; D020024:Leukotriene Antagonists; D015289:Leukotrienes / Q000378:metabolism; D009926:Organ Preservation / Q000379:methods*; D019188:Organ Preservation Solutions; D011725:Pyridines / Q000494:pharmacology; D011887:Raffinose; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism
D001572:Benzofurans; D004791:Enzyme Inhibitors; D007093:Imidazoles; D007328:Insulin; D020024:Leukotriene Antagonists; D015289:Leukotrienes; D019188:Organ Preservation Solutions; D011725:Pyridines; C055206:University of Wisconsin-lactobionate solution; D016718:Arachidonic Acid; D000493:Allopurinol; C049113:3-methyl-2-(3-pyridyl)-1-indoleoctanoic acid; C037787:pirmagrel; D013930:Thromboxane-A Synthase; D005978:Glutathione; D000241:Adenosine; C039936:furegrelate; D011887:Raffinose; D001241:Aspirin; D007052:Ibuprofen