REMOVAL OF PLATELET-ACTIVATING-FACTOR IN EXPERIMENTAL CONTINUOUS ARTERIOVENOUS HEMOFILTRATION

Objective: There is a positive correlation between the amount of ultra filtration and the improved survival rate of patients with ischemia or sepsis-induced acute renal failure. Continuous arteriovenous hemofilt ration (CAVH) removes vasoactive substances with a molecular weight of <1000 daltons, This study evaluated the removal of platelet-activatin g factor, a lipid mediator of endotoxic shock, by CAVH with respect to kinetics, adsorption, and ultrafiltration. Design: Prospective labora tory study. Subjects: Normal human subjects. Interventions: Radioactiv e [H-3] or biologically active platelet-activating factor was added to whole blood or washed blood resuspended in Tris-buffered (pH 7.2) phy siologic saline with 4% human serum albumin or plasma. Whole or washed blood cells or plasma were recirculated at 100 mL/min through polysul fone hemofilters for 120 mins with ultrafiltration (condition A), with out ultrafiltration (condition B), or in a static condition (condition C). Concentrations of albumin, total protein, and radioactive or biol ogically active platelet-activating factor in samples obtained from th e blood and ultrafiltrate compartment were determined. Measurements: B iologically active platelet-activating factor was quantified on washed rabbit platelets and results were expressed in ng/mL over a calibrati on curve obtained with synthetic platelet-activating factor. Main Resu lts: [H-3]-platelet-activating factor added to recirculated whole bloo d was ultrafiltered (percent of ultrafiltered platelet-activating fact or/min: 0.48 +/- 0.02 [SD]; total platelet-activating factor removed i n 120 mins: 15.52%; condition A) at significantly (p < .001) higher am ounts than when added to washed blood cells (percent of ultrafiltered platelet-activating factor removed/min: 0.195 +/- 0.06; total platelet -activating factor removed in 120 mins: 7.46%). The highest amounts of [H-3]-platelet-activating factor were bound to polysulfone membranes after recirculation with whole blood (44.5 +/- 12.2%) than with washed blood (1.1 +/- 0.3%) or plasma (11.9 +/- 0.7%). Biologically active p latelet-activating factor concentrations significantly decreased in bo th conditions A and B (maximal decrease at 120 mins: 63% and 59%, resp ectively). No significant reduction could be observed in condition C. Conclusions: These studies provide experimental evidence for the promp t, efficient removal of platelet-activating factor in CAVH and provide a possible rationale for the beneficial effect of this therapy in the development of multiple organ failure in sepsis.