title: Neutrophils accentuate renal cold ischemia-reperfusion injury. Dose-dependent protective effect of a platelet-activating factor receptor antagonist.
abstract: This study was undertaken to evaluate whether the renal damage induced by cold ischemia-reperfusion was worsened by neutrophils (PMN), and if blockade of platelet-activating factor (PAF) could effectively decrease this injury. After flushing with EuroCollins, 85 kidneys from Sprague-Dawley rats underwent either no cold ischemia or a 4-h cold ischemia, and then were reperfused for 75 min at 37 degrees C and 100 mm Hg in an isolated perfusion circuit. Reperfusion was performed with a Krebs-Henseleit solution containing 4.5% albumin, with and without human PMN (7.5 x 10(5) cells/ml) and with and without addition of a PAF receptor antagonist (BN 52021). Hemodynamic and functional parameters were continuously assessed during reperfusion. At end of the study, PAF production was evaluated. Presence of PMN during reperfusion of nonischemic kidneys produced no alteration of functional parameters or PAF production. After 4-h cold ischemia, the presence of PMN during reperfusion produced a significant worsening of plasma flow rate, glomerular filtration rate and sodium reabsorption in comparison with kidneys reperfused without PMN. Also, higher production of PAF was observed in the kidneys reperfused with PMN than in the kidneys reperfused without PMN. After 4-h cold ischemia, addition of BN 52021 during reperfusion in the presence of PMN significantly increased the plasma flow rate, glomerular filtration rate and sodium reabsorption in comparison with kidneys reperfused without this PAF antagonist. This effect was dose dependent. After 4-h cold ischemia, addition of BN 52021 during reperfusion in the absence of PMN produced no significant effect on functional parameters in comparison with kidneys reperfused without this PAF antagonist. These results indicate that PMN contribute to renal cold ischemia-reperfusion injury evaluated in the isolated perfused kidney. Treatment with a PAF receptor antagonist attenuated this injury in a dose-dependent manner, which suggests that it is mediated by PAF.
authors.affiliation: Fundació August Pi i Sunyer, Ciutat Sanitarià i Universitària de Bellvitge, Barcelona, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Riera
authors.forename: J
authors.initials: J
authors.lastname: Torras
authors.forename: I
authors.initials: I
authors.lastname: Herrero
authors.forename: J
authors.initials: J
authors.lastname: Valles
authors.forename: M
authors.initials: M
authors.lastname: Paubert-Braquet
authors.forename: J M
authors.initials: JM
authors.lastname: Cruzado
authors.forename: J
authors.initials: J
authors.lastname: Alsina
authors.forename: J M
authors.initials: JM
authors.lastname: Grinyo
mesh_terms: D000818:Animals; D003080:Cold Temperature; D004224:Diterpenes; D005343:Fibrinolytic Agents / Q000494:pharmacology; D046934:Ginkgolides; D005919:Glomerular Filtration Rate / Q000187:drug effects; D005947:Glucose; D006801:Humans; D006982:Hypertonic Solutions; D066298:In Vitro Techniques; D007668:Kidney / Q000098:blood supply* / Q000187:drug effects / Q000502:physiology; D007783:Lactones / Q000494:pharmacology*; D008297:Male; D009504:Neutrophils / Q000502:physiology*; D009926:Organ Preservation; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects; D015427:Reperfusion Injury / Q000503:physiopathology* / Q000517:prevention & control*; D014325:Tromethamine; D014655:Vascular Resistance / Q000187:drug effects
chemical_list: D004224:Diterpenes; C037096:Euro-Collins' solution; D005343:Fibrinolytic Agents; D046934:Ginkgolides; D006982:Hypertonic Solutions; C074097:Krebs-Henseleit solution; D007783:Lactones; D010972:Platelet Activating Factor; D014325:Tromethamine; C045856:ginkgolide B; D005947:Glucose