DESIGN OF A BIOMEDICAL REACTOR FOR PLASMA LOW-DENSITY-LIPOPROTEIN REMOVAL

The purpose of this study was to design a biomedical reactor that redu ces plasma cholesterol when incorporated in an in vivo extracorporeal system. Phospholipase A2, immobilized onto Agarose beads and housed in side the bioreactor, modifies plasma low density lipoprotein (LDL) int o a form that is rapidly removed from circulation. In a packed bed rea ctor, the enzymatic conversion of LDL to the modified form (with plasm a taken from hypercholesterolemic New Zealand white rabbits) was relat ively low, 25% +/- 6 for a single pass of plasma through the reactor. An extended bed reactor, a hybrid of fluidized and packed bed reactors , was then developed to increase the conversion. This reactor displays a single pass conversion of 60% +/- 5 under optimal flow conditions. An evaluation of the flow rate through the reactor indicates that the system is limited by external mass transfer when employed under in viv o conditions. In addition, this system requires blood separation befor e the enzyme modification, which complicates the circuit control. Ther efore, a new system was designed for in vivo use with rabbits. The res ulting design, called the plasma separator reactor (PSR), combines pla sma separation and enzymatic conversion in a single chamber. The PSR h as three advantages over other studied systems: improved external mass transfer conditions, easy controlability, and simple set-up procedure s. Single pass conversion reached 52% +/- 12 in suboptimal flow under simulated in vivo conditions. This reactor was also tested in vivo wit h hypercholesterolemic New Zealand white rabbits. A continuous convers ion of up to 80% +/- 6 of rabbit plasma phospholipids was observed dur ing 90 min of blood circulation (5 mL/min). The decrease in total plas ma cholesterol reached a level of 60% of the initial value and was obs erved to be a function of the bioreactor enzyme activity. (C) 1993 Joh n Wiley & Sons, Inc.