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Removal of platelet-activating factor in experimental continuous arteriovenous hemofiltration

Ronco, Claudio MD; Tetta, Ciro MD; Lupi, Alessandro MD; Galloni, Elisabetta MA; Bettini, Maria Costanza MD; Sereni, Luisa MA; Mariano, Filippo MD; DeMartino, Antonella BA; Montrucchio, Giuseppe MD; Camussi, Giovanni MD; La Greca, Giuseppe MD

Laboratory Investigation

Objective: There is a positive correlation between the amount of ultrafiltration and the improved survival rate of patients with ischemia or sepsis-induced acute renal failure. Continuous arteriovenous hemofiltration (CAVH) removes vasoactive substances with a molecular weight of less than 1000 daltons. This study evaluated the removal of platelet-activating factor, a lipid mediator of endotoxic shock, by CAVH with respect to kinetics, adsorption, and ultrafiltration.

Design: Prospective laboratory study.

Subjects: Normal human subjects.

Interventions: Radioactive [sup 3 H] or biologically active platelet-activating factor was added to whole blood or washed blood resuspended in Tris-buffered (pH 7.2) physiologic saline with 4% human serum albumin or plasma. Whole or washed blood cells or plasma were recirculated at 100 mL/min through polysulfone hemofilters for 120 mins with ultrafiltration (condition A), without ultrafiltration (condition B), or in a static condition (condition C). Concentrations of albumin, total protein, and radioactive or biologically active platelet-activating factor in samples obtained from the blood and ultrafiltrate compartment were determined.

Measurements: Biologically active platelet-activating factor was quantified on washed rabbit platelets and results were expressed in ng/mL over a calibration curve obtained with synthetic platelet-activating factor.

Main Results: [sup 3 H]-platelet-activating factor added to recirculated whole blood was ultrafiltered (percent of ultrafiltered platelet-activating factor/min: 0.48 plus minus 0.02 [SD]; total platelet-activating factor removed in 120 mins: 15.52%; condition A) at significantly (p less than .001) higher amounts than when added to washed blood cells (percent of ultrafiltered platelet-activating factor removed/min: 0.195 plus minus 0.06; total platelet-activating factor removed in 120 mins: 7.46%). The highest amounts of [sup 3 H]-platelet-activating factor were bound to polysulfone membranes after recirculation with whole blood (44.5 plus minus 12.2%) than with washed blood (1.1 plus minus 0.3%) or plasma (11.9 plus minus 0.7%). Biologically active platelet-activating factor concentrations significantly decreased in both conditions A and B (maximal decrease at 120 mins: 63% and 59%, respectively). No significant reduction could be observed in condition C.

Conclusions: These studies provide experimental evidence for the prompt, 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.

(Crit Care Med 1995; 23:99-107)

From the Department of Nephrology and Dialysis (Drs. Ronco and La Greca), the Department of Nuclear Medicine (Dr. Lupi and Ms. Galloni), and the Department of Immunohematology (Dr. Bettini), S. Bortolo Hospital, Vicenza, Italy; Chair of Nephrology, I Faculty of Medicine and Surgery (Drs. Mariano, Montrucchio, and Camussi and Ms. DeMartino), University of Naples, Napoli, Italy; Bellco Research Laboratories and Clinical Research Department (Dr. Tetta and Ms. Sereni), Bellco S.p.A., Mirandola, Modena, Italy.

This work was supported, in part, by a grant of the National Research Council (CNR). Targeted project: Prevention and control disease factors; subproject: Causes of infection-related diseases (CT 9300607, PF41) to G. Camussi.

Address requests for reprints to: Ciro Tetta, MD, Bellco Research Laboratories, Via Camurana, 1/A Mirandola, Modena, Italy.

© Williams & Wilkins 1995. All Rights Reserved.