Cholesterol removal by haemoperfusion of whole blood in vivo.
Familial hypercholesterolaemia is caused by genetic defects in the cellular metabolism of cholesterol (C) and is characterized by high levels of low-density lipoproteins (LDL) and premature atherosclerosis. The C is carried in the plasma mainly as an LDL-C complex, and removal of the latter from plasma is highly desirable. This task can be achieved by selective haemoperfusion (HP), thereby eliminating the need for plasmapheresis. Agarose beads (2 per cent agarose, 0.85 to 1.4 mm in diameter) were prepared, and crosslinked with epichlorohydrin. Heparin and/or ethanolamine were subsequently attached. The beads thus obtained were found to be suitable for the removal of LDL-C from the whole blood of hypercholesterolaemic rabbits, using a simple HP technique. A single two-hour HP treatment with a 40 ml column packed with active agarose beads resulted in a 30 per cent decrease in the C plasma level in the experimental animals. Our previous, in vitro, studies with the plasma of hypercholesterolaemic patients showed a high selectivity of the beads for LDL. Yet when used with hypercholesterolaemic rabbits, a relatively high amount of HDL was also removed from the blood. This can be attributed to a significant difference between the structure of human hypercholesterolaemic lipoproteins and that of rabbits. Upon treatment of blood using the active agarose beads, no abnormalities in plasma and blood composition were detected, except for some prolongation of PT. It is to be hoped that this new system will replace the presently used and highly expensive plasmapheresis.