Treatment of hypercholesterolemia by chemical adsorption of lipoproteins

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Abstract
Dextran sulfate (Mr 5,000) was covalently linked to porous cellulose beads, and the dissociation constant (Kd) and the maximum binding level (S) of the beads were calculated for the human plasma lipoproteins VLDL, LDL, and HDL. The S values for VLDL and LDL were 2 and 7 g cholesterol/liter of the wet beads and that for HDL was almost negligible, although the apparent Kd were all in the same order. In fact, LDL and VLDL were exclusively adsorbed by the beads from human plasma in vitro. Bound LDL was desorbed with 0.35 M Nacl. The beads were packed in a column (25‐ml) and used with polysulfone hollow fibers in experimental LDL‐apheresis for WHHL rabbits; LDL cholesterol was reduced from 500 to 200 mg/dl, while HDL, total plasma protein, and major blood cell counts did not change.For LDL apheresis of familial hypercholesterolemia, the sorbent column, 400‐ml, was used with the polysulfone hollow fiber filter. The maximum removal of LDL + VLDL cholesterol was 6 to 8 g with a single column resulting in its reduction by 250 to 300 mg/dl after 3.5 liters plasma treatment. Adsorption was negligible with albumin, HDL, IgA, G, M, apoA‐I, A‐II, C‐II, enzymes, and electrolytes. Activated complement fragments, C3a, and Csa, were completely adsorbed. By periodic removal of LDL, an increase of HDL cholesterol was observed in some cases. In order to increase LDL removal in a single treatment and to reduce the extracorporeal circulation volume, two small columns (150 ml each) were used alternatively. The column saturated with LDL was washed with 0.7 M NaCl for regeneration while the other column was used. LDL + VLDL cholesterol decreased linearly to the treated plasma volume in semilogarithmic plot, showing that the LDL removal was optimized in mis system.

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