LOW-DENSITY LIPOPROTEIN-APOLIPOPROTEIN-B METABOLISM FOLLOWING APHERESIS - SIMULATION STUDIES OF MASS CHANGES AND TRACER KINETICS

Low-density lipoprotein (LDL) apheresis is an effective method to trea t severe hyperlipoproteinemia such as heterozygous familiar hyperchole sterolemia (FH). It is unknown whether apheresis induces changes in me tabolic parameters of LDL-apolipoprotein B (apoB) such as the fraction al catabolic rate (FCR) or production rate, We performed simulation st udies to determine the effect of potential changes in the LDL FCR on L DL-apoB mass and on exogenous and endogenous tracer studies, For these studies, we assumed a two-compartment LDL model and the following met abolic parameters: plasma LDL-apoB, 180 mg.dL(-1); LDL-apoB production rate, 36 mg.dL(-1).d(-1) (approximate to 14.4 mg.kg(-1).d(-1)); and L DL-apo FCR, 0.2 d(-1). It was also assumed that apheresis instantaneou sly decreased the LDL-apoB concentration to 60 mg.dL(-1) and that LDL- apoB production was not perturbed, The simulations examined three poss ible outcomes: (1) no change in FCR, (2) a temporary doubling in FCR, and (3) a temporary tripling in FCR. Monoexponential models were fit t o the rebound of LDL-apoB mass data generated using the different FCRs . In no instance did the FCR determined from the fit match the FCR use d to generate the data: FCRs were either higher or lower than the orig inal FCR used to generate the data, Simulations of the kinetics of exo genously labeled LDL showed that if apheresis was performed on day 7 o f a turnover study, it would be possible to detect large changes in LD L-apoB FCR. In contrast, during an endogenous labeling study, potentia l increases in FCR induced by apheresis may not be detected, However, our simulations do show that endogenous labeling studies performed bef ore and after apheresis should yield data that will permit detection o f changes in the FCR, Thus, these studies indicate that large differen ces in the LDL-apoB FCR induced by apheresis can be detected by either an exogenous tracer experiment perturbed by apheresis or by endogenou s labeling experiments performed before and after apheresis, Small cha nges in the FCR that may be induced by apheresis will probably be indi stinguishable from experimental noise. Copyright (C) 1998 by W.B. Saun ders Company.