Rat extracorporeal circulation model for evaluation of systemic immunotoxicity

We have applied a rat extracorporeal circulation (EC) model as an evaluatio n system for the immunotoxicity of medical devices in contact with the bloo d stream. Combining popular hemodialysis (HD) membranes [a non-biocompatibl e membrane, Cupurophane(R) (CUP), and more biocompatible membranes, Cu-ammo nium rayon (CAR) and polyacrylonitrile (PAN)] with rat EC, we evaluated the elicitation of acute and delayed immunological responses, as well as the e ffect of repeated EC. Acute effect markers such as the production of tumor necrosis factor (TNF)-alpha and complement activity during EC, and delayed effect markers such as beta(2)-microglobulin (beta(2)-M), IgG, and compleme nt 3 levels, were monitored. Acute markers after EC passage showed response s similar to those previously reported in patients with long-term hemodialy sis such as TNF-alpha production and increased complement activity. Althoug h beta(2)-M and IgG levels increased to 3- to 5-fold of the initial concent ration within 4 weeks after rat EC, the trend of IgG increase was inversely correlated with membrane biocompatibility (CUP > CAR = PAN), but this did not occur for elevations in beta(2)-M (PAN > CAR > CUP). These data suggest that this EC model can reproduce similar immunological responses as seen i n HD patients, and can be employed to evaluate medical devices and material s for their delayed, systemic, and repeated exposure effects with respect t o immunotoxicity. (C) 2000 Elsevier Science Ireland Ltd. All rights reserve d.