MECHANISMS AND KINETICS OF THE SYNTHESIS AND RELEASE OF PLATELET-ACTIVATING-FACTOR (PAF) BY POLYACRYLONITRILE MEMBRANES

Platelet-activating factor is a recognized mediator of anaphylaxis and bioincompatibility. Here, the mechanisms and the kinetics of the prod uction of platelet-activating factor were studied in vivo during high- flux hemodialysis and in vitro in a recirculation model with polyacryl onitrile membranes. the AN-69 and the more recent SPAN, where the Na-m etallilsulfonate group is partially substituted with the less polar me thacrylate group. in in vivo studies, eleven patients were studied in cross over, Patients were randomly allocated to the AN-69 (5 patients) and to the SPAN membrane (6 patients) for two weeks. Measurements wer e made in the second week of use, After completion of the second week, the patients were switched to the other membrane for a further two we eks. Samples for leukocyte and platelet counts, PAF in whole blood or bound to platelets, the C3a des Arg and the C5b-C9 membrane attach com plex as well as samples for clearances of urea, creatinine and phospha tes were taken at different time intervals during treatment. PAF was d etected by biological assay after methanol extraction of whole blood o r of platelet pellets obtained by sequential centrifugation. C3a des A rg and the C5b-C9 fraction were detected by commercially available imm unoassays. Results were analyzed by Minitab statistical package. PAF w as detectable only during treatment with AN-69 but not with SPAN 1 min after start of the extracorporeal circulation in both whole blood (4. 5 +/- 2.7 ng/ml) and on platelet surface (4.1 +/- 1.2 ng/ml). No stati stical significant differences were observed between AN-69 and SPAN wi th regard to leukocyte and platelet counts, plasma C3a des Arg and C5b -C9 levels. The structure modification did not alter functional perfor mances as indicated by the lack of statistically significant differenc es in clearance values between the two membranes. In in vitro experime nts performed with normal washed and whole blood recirculated in a clo sed circuit demonstrated the presence of a plasma-dependent, complemen t-independent mechanisms responsible for the triggering of PAF synthes is and release with AN-69 but not SPAN membrane. PAF was extractable f rom the inner and outer side of both polyacrylonitrile membranes (AN-6 9: inner, 4.9 +/- 0.5 ng/ml; outer, 0.1 +/- 0.005 ng/ml; SPAN: inner, 5.5 +/- 0.6 ng/ml, outer: 3.3 +/- 0.7 ng/ml, SPAN vs, p <0.001), sugge sting that absorption may be relevant with both membranes.