NEUTROPHILS ACCENTUATE RENAL COLD ISCHEMIA-REPERFUSION INJURY - DOSE-DEPENDENT PROTECTIVE EFFECT OF A PLATELET-ACTIVATING-FACTOR RECEPTOR ANTAGONIST

This study was undertaken to evaluate whether the renal damage induced by cold ischemia-reperfusion was worsened by neutrophils (PMN), and i f blockade of platelet-activating factor (PAF) could effectively decre ase this injury. After flushing with EuroCollins, 85 kidneys from Spra gue-Dawley rats underwent either no cold ischemia or a 4-h cold ischem ia, 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 Kre bs-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 rece ptor antagonist (BN 52021). Hemodynamic and functional parameters were continuously assessed during reperfusion. At end of the study, PAF pr oduction was evaluated. Presence of PMN during reperfusion of nonische mic kidneys produced no alteration of functional parameters or PAF pro duction. After 4-h cold ischemia, the presence of PMN during reperfusi on produced a significant worsening of plasma flow rate, glomerular fi ltration rate and sodium reabsorption in comparison with kidneys reper fused 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, glom erular filtration rate and sodium reabsorption in comparison with kidn eys reperfused without this PAF antagonist. This effect was dose depen dent. After 4-h cold ischemia, addition of BN 52021 during reperfusion in the absence of PMN produced no significant effect on functional pa rameters in comparison with kidneys reperfused without this PAF antago nist. These results indicate that PMN contribute to renal cold ischemi a-reperfusion injury evaluated in the isolated perfused kidney. Treatm ent with a PAF receptor antagonist attenuated this injury in a dose-de pendent manner, which suggests that it is mediated by PAF.