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°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 × 105 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.
Footnotes
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Send reprint requests to: J. M. Grinyo, Nephrology Service, Hospital of Bellvitge, Ciutat Sanitària i Universitària de Bellvitge, Feixa Llarga s/n, 08097 L’Hospitalet de Llobregat, Barcelona, Spain.
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↵1 This work was supported in part by a grant from FISS (number 94/1296) and by a grant from LASA Laboratories. Part of this papper was orally presented at 7th Congress of European Society for Organ Transplantation, Vienna, October 1995.
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↵2 Marta Riera Oliva is a fellow from “FundacióAugust Pi i Sunyer,” Ciutat Sanitaria i Universitaria de Bellvitge.
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↵3 Immaculada Herrero Fresneda is a fellow from LASA Laboratories.
- Abbreviations:
- EC
- Euro-Collins solution
- EDTA
- ethylenediaminetetraacetic acid
- FF
- filtration fraction
- FRNa
- fractional sodium reabsorption
- GFR
- glomerular filtration rate
- PAF
- platelet-activating factor
- PMN
- polymorphonuclear cells
- PFR
- plasma flow rate
- QO2
- oxygen consumption
- RVR
- renal vascular resistance
- TNa
- net sodium reabsortion
- RIA
- radioimmunoassay
- Received May 6, 1996.
- Accepted October 24, 1996.
- The American Society for Pharmacology and Experimental Therapeutics
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