In a previous study (1) heparin was found to inhibit the rise of plasma lipids and cholesterol occurring in rats with nephrosis experimentally induced by injection of anti-rat kidney serum (AKS). Such inhibition was marked when heparin was administered prior to and immediately after the injection of AKS, but of much lesser degree when administered to the chronic nephrotic rat with established hypoalbuminemia and hyperlipemia. A similar slight or absent anti-lipemic response to heparin has been observed in some human subjects with nephrosis (2). This suggested to us that perhaps the inhibitory action of heparin necessitated the presence of a larger concentration of plasma albumin than was present in the chronic nephrotic rat.Therefore a second study (3) was done in which bovine serum albumin was infused into rats during both the induction and chronic phases of experimental nephrosis. This was found to be far more effective than heparin in respectively preventing and correcting the hyperlipemia otherwise occurring in such rats. However, the infusion of albumin was not found capable of completely normalizing the plasma lipids of the nephrotic animal unless it concomitantly was nephrectomized.This suggested that the accumulation of lipids in the plasma of the nephrotic rat is due not only to a quantitative deficiency of plasma albumin (3) but also to the excessive renal loss of some other essential plasma constituent of the lipid-clearing mechanism which might be escaping pan passu, either separately or combined with the escaping albumin. If this substance were heparin, or its plasma equivalent, the combined administration of heparin and albumin would be expected to be 'Aided by Grants from the National Institute of Arthritis and Metabolic Diseases of the National Institutes of Health, (A-46, C-4), the American Heart Association and the San Francisco Heart Association.completely effective in normalizing the plasma lipids of the nephrotic rat. This was found to be true in the present study of such combined treatment, the data also providing an in vivo demonstration of the essential role of adequate plasma albumin for both endogenous and heparin-activated processes of lipemia-clearing.
METHODS AND RESULTSAdult, male rats (Long-Evans) were used in these studies. Pooled rabbit anti-rat kidney serum (AKS) was prepared as described by Heymann and Lund (4) and assayed in preliminary studies by its ability to induce hypoalbuminemia, hyperlipemia and hypercholesteremia within 18 hours after its intravenous injection. Continuous intravenous infusions were administered by a special constant infusion apparatus designed to inject 0.25 ml.per hour (6.0 ml. per 24 hours) through an exteriorized polyethylene cannula placed in an inferior lumbar vein during a preliminary operation accomplished under ether anesthesia. The injected solutions were either freshly prepared aqueous bovine serum albumin (30 per cent) or sodium chloride (0.9 per cent), the latter being used since it was previously found to induce a degree of hemodilution in...