PROTECTIVE EFFECT OF A PLATELET-ACTIVATING-FACTOR ANTAGONIST (WEB-2086) IN POSTISCHEMIC RENAL-FAILURE

The purpose of this study was to evaluate the renoprotective effect of a specific platelet-activating factor antagonist (WEB-2086) in an exp erimental model of normothermic renal ischemia. Twenty New Zealand whi te rabbits were studied for 2 days before and 24 hours after a 60-minu te period of renal ischemia induced by bilateral clamping of the renal arteries. The animals were divided into two groups: a control group ( group A; n = 10) and a treated group (group B; n = 10). In group A the urinary flow rate decreased significantly (from 0.098 +/- 0.008 ml/mi n to 0.029 +/- 0.005 ml/min) (p < 0.001) and there was a significant r eduction in creatinine clearance (from 11.4 +/- 1.2 ml/min to 3.4 +/- 1.1 ml/min) (p <0.001). In group B no significant changes were observe d, although the urinary flow rate increased even in the postischemic p eriod (from 0.09 +/- 0.008 ml/min to 0.11 +/- 0.02 ml/min). Microcircu latory cortical flow showed a postischemic reduction in both groups, a lthough it was most significant in the control group (group A = 43.7%, group B = 71.5%; p <0.001). Histologic study showed mild damage with patchy tubular necrosis in both groups, although this injury was less severe in the treated group. The results suggest that the preoperative administration of WEB-2086 produces a potent diuretic effect with sig nificant attenuation of postischemic acute renal failure.