Removal of platelet-activating factor in experimental continuous arteriovenous hemofiltration.
ABSTRACT 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.
Prospective laboratory study.
Normal human subjects.
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.
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.
[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.
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.
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ABSTRACT: One hundred ten critically ill patients with acute renal failure receiving acute continuous hemodiafiltration (ACHD) in our intensive care unit were studied prospectively. Acute continuous hemodiafiltration consisted either of continuous arteriovenous hemodiafiltration or of continuous veno-venous hemodiafiltration, and was used for 17,817 hours (mean duration of patient treatment, 161.9 hours), resulting in a fall from a mean pre-ACHD urea of 35.7 mmol/L to a plateau value of 16.8 mmol/L at 72 hours of treatment. The mean urea clearance achieved was 24.9 mL/min. Eighty of these patients (72.7%) were receiving artificial ventilation at the time of ACHD and 45 (40.9%) had more than four failing organs. The mean APACHE II score was 27.7. Despite the degree of illness severity, 42 patients (32.2%) survived to discharge from hospital. The use of ACHD was associated with hemodynamic stability, rapid normalization of electrolytes, and the ability to freely administer drugs, blood, and/or blood products. It also allowed for maintenance of an aggressive, nitrogen-rich, nutritional regimen. Support of these critically ill patients with acute renal failure using ACHD was achieved safely and without the employment of additional dialysis-trained nursing staff. Our own experience and a review of the available literature strongly suggest that the advantages associated with the use of ACHD therapies are clinically significant and support the view that ACHD is a modality of renal replacement most suited to critically ill patients with acute renal failure.American Journal of Kidney Diseases 06/1993; 21(5):508-18. · 5.29 Impact Factor
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ABSTRACT: Platelet-activating factors (PAF), a phospholipid mediator of anaphylaxis, is also known to be released in vitro from both phagocytic polymorphonuclear neutrophils (PMN) and monocytes in response to a variety of stimuli. The fact that human myeloid cells of the HL-60 line can be made to differentiate in vitro into macrophage-like cells by 12-O-tetradodecanoylphorbol-13-acetate (TPA) prompted us to investigate the generation and release of PAF during this transformation. Both passive release of PAF at pH 9.5, and active release, following phagocytosis of C3b- and C3d-opsonized yeast spores, and stimulation with C5a anaphylatoxin from untreated and TPA-treated HL-60 cells, PMN, and plastic-adherent normal human monocytes were studied. It was found that after 3 days of TPA treatment, HL-60 cells released PAF following phagocytosis of C3b- and C3d-opsonized yeast spores. Inhibition of PAF release by a selective inhibitor of phospholipase A2 and labeling of PAF with sodium 14C-acetate indicated that PAF generation is a two-step process: (1) release of PAF precursor from cell membranes and (2) its acetylation. A model for the in vivo study of mechanisms and metabolic events involved in PAF generation and release could perhaps be built on these findings.UBlood 02/1982; 59(1):16-22. · 9.06 Impact Factor
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ABSTRACT: The biologically active 1-O-alkyl-2-acetyl-sn-glyceryl-3-phosphorylcholine (platelet-activating factor; PAF) is inactivated in plasma mainly by a specific PAF acetylhydrolase (1-alkyl-2-acetyl-sn-glyceryl-3-phosphorylcholine acetylhydrolase; EC 220.127.116.11). In the present study, PAF was released in detectable amounts (5.4 +/- 2.9 ng/ml; mean +/- 1 SD) in the plasma of 8 out of 10 patients with systemic lupus erythematosus (SLE) during the most active phases of the disease. PAF was never detectable in the plasma of patients with inactive SLE or of healthy subjects. PAF acetylhydrolase activity was markedly reduced in sera of 10 patients with active SLE as compared to 7 patients with inactive SLE, 16 patients with rheumatoid arthritis (RA), 5 patients with nephrotic syndrome (NS) and 15 healthy subjects. A kinetic study of the enzyme in patients with active SLE suggested an overall reduced activity rather than an intrinsic defect of the enzyme. PAF acetylhydrolase in sera of patients with active SLE shared with that of healthy subjects the same substrate specificity, sensitivity to enzymatic and chemicophysical treatments and association to low-density lipoprotein (LDL), acting as carrier of PAF acetylhydrolase in plasma. However, the protein concentration of LDL was significantly reduced in patients with active SLE as compared to patients with inactive SLE, RA and NS and to healthy subjects, thereby suggesting that the reduction of PAF acetylhydrolase activity in active SLE might be due at least in part to a carrier defect related to the activity of the disease. In addition, experiments in which serum of patients with active SLE and serum of healthy subjects were mixed in different combinations indicated the absence of factors inhibiting PAF acetylhydrolase activity in SLE patients.International archives of allergy and applied immunology 02/1990; 91(3):244-56.