Removal of platelet-activating factor in experimental continuous arteriovenous hemofiltration.
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 < 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.


METHODS
Prospective laboratory study.


METHODS
Normal human subjects.


METHODS
Radioactive [3H] 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.


METHODS
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.


RESULTS
[3H]-platelet-activating factor added to recirculated whole blood was ultrafiltered (percent of ultrafiltered platelet-activating factor/min: 0.48 +/- 0.02 [SD]; total platelet-activating factor removed in 120 mins: 15.52%; condition A) at significantly (p < .001) higher amounts 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 [3H]-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 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.
Ronco
C
C
Department of Nephrology and Dialysis, S. Bortolo Hospital, Vicenza, Italy.
Tetta
C
C
Lupi
A
A
Galloni
E
E
Bettini
M C
MC
Sereni
L
L
Mariano
F
F
DeMartino
A
A
Montrucchio
G
G
Camussi
G
G
D000327:Adsorption; D006440:Hemofiltration; D006801:Humans; D066298:In Vitro Techniques; D008567:Membranes, Artificial; D010972:Platelet Activating Factor / Q000032:analysis*; D011108:Polymers; D011446:Prospective Studies; D012709:Serum Albumin / Q000032:analysis; D013450:Sulfones; D014462:Ultrafiltration
D008567:Membranes, Artificial; D010972:Platelet Activating Factor; D011108:Polymers; D012709:Serum Albumin; D013450:Sulfones; C017662:polysulfone P 1700