title: Long-term renal preservation and prevention of acute tubular necrosis by inhibition of arachidonate metabolism.
abstract: 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.
authors.affiliation: Departement für Viszerale- und Transplantationschirurgie, Universität, Bern, Inselspital.
authors.forename: M
authors.initials: M
authors.lastname: Schilling
authors.forename: A
authors.initials: A
authors.lastname: Saunder
authors.forename: J H
authors.initials: JH
authors.lastname: Southard
authors.forename: F O
authors.initials: FO
authors.lastname: Belzer
mesh_terms: 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
chemical_list: 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