title: The effect of aprotinin on ischemia-reperfusion injury in the rabbit kidney.
abstract: Tissue subjected to a period of ischemia undergoes functional and morphological damage that increases during the reperfusion phase. In this study, the protective effect of aprotinin, which is a protease inhibitor, was assessed in a rabbit unilateral renal ischemia-reperfusion (I/R) model. New Zealand rabbits, weighing 1.5-2 kg, were randomized to receive either aprotinin 30.000 KIU x kg(-1) and 10.000 KIU x kg(-1) x h(-1) i.v. infusion (group I, n= 7) or equivalent volumes of 0.09% sodium chloride (SF) (group II, control, n= 7) i.v. 15 minutes before a 45 minutes interruption of left renal artery blood flow and then 45 minutes of reperfusion. Blood samples were obtained before and after the ischemia-reperfusion period for measurement of nitric oxide serum (NO) levels with the nitrite/nitrate colorimetric method. Histological changes were evaluated by quantitative measurements using a numerical score (0-4) and immunohistochemical analysis of inducible nitric oxide synthase (iNOS) expression was determined. A Wilcoxon W -test was used for statistical analysis of biochemical measurements and mean values were expressed as +/-sd. Histological examination revealed the distinctive pattern of ischemic renal tissue injury with obvious signs of epithelial necrosis. The intensity of epithelial necrosis was more extensive in the SF group. Immunohistochemical analysis showed that there was severe immunostaining in the tubular epithelium in both cortical and medullary regions and iNOS expression was more intense in SF-only cases. The staining results for aprotinin cases did not differ much from the non-ischemic kidney. Biochemical analysis revealed an increase in serum NO levels in both groups (P< 0.05), but this was more evident in the SF group (mean NO levels were 38.63 +/- 19.03 micromol x L(-1) in group I, 50.63 +/- 24.28 micromol x L(-1) in group II). No statistically important difference was observed between the two groups. These results suggest that aprotinin may be beneficial in the prevention of systemic inflammation after transient renal ischemia.
authors.affiliation: Department of Anaesthesiology and Reanimation, University of Mersin, Turkey. zozerkocak@hotmail.com
authors.forename: Z
authors.initials: Z
authors.lastname: Ozer
authors.forename: N
authors.initials: N
authors.lastname: Sucu
authors.forename: D
authors.initials: D
authors.lastname: Düşmez
authors.forename: L
authors.initials: L
authors.lastname: Tamer
authors.forename: A A
authors.initials: AA
authors.lastname: Altunkan
authors.forename: M
authors.initials: M
authors.lastname: DIkmengIl
authors.forename: U
authors.initials: U
authors.lastname: Oral
mesh_terms: D000818:Animals; D007611:Aprotinin / Q000378:metabolism / Q000494:pharmacology*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005260:Female; D007150:Immunohistochemistry; D007511:Ischemia / Q000378:metabolism*; D007668:Kidney / Q000098:blood supply* / Q000473:pathology; D009336:Necrosis; D009569:Nitric Oxide / Q000096:biosynthesis / Q000097:blood; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D011817:Rabbits; D015427:Reperfusion Injury / Q000378:metabolism*; D015842:Serine Proteinase Inhibitors / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D016207:Cytokines; D015842:Serine Proteinase Inhibitors; D009569:Nitric Oxide; D007611:Aprotinin; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II