The two recognized systems of total parenteral nutrition (TPN), one consisting of glucose, amino acid and fat (Liposyn)-lipid TPN the other consisting of glucose amino acid without added fat (glucose TPN) and parenteral phospholipid (PPL) infusion have strikingly different effects on plasma cholesterol concentrations. Glucose-TPN causes a 35 percent decrease in total plasma cholesterol while lipid-TPN results in a six fold increase in plasma free cholesterol. Parenteral phospholipid infusion (Lipostabil) on the other hand causes a 12 percent fall in total plasma cholesterol while significantly raising the HLD/LKL radio. The mechanism(s) by which any parenteral system causing these documented changes in plasma cholesterol levels is not known, nor is it known if they have any significant effect on the mass of the total exchangeable cholesterol pool in man. We propose to study the effects of both TPN systems, as well as PPl infusion, on the key parameters of cholesterol homeostasis in man: fecal acidic and neutral sterol excretion, bile acid pool size, biliary composition and flow rate, plasma lecithin cholesterol acyl transferase (LCAT) activity, mononuclear leukocyte cholesterol ester hydrolase (CEH) and acyl-CoA cholesterol acyl transferase (ACAT) activity, and the mass of the rapidly exchangeable and total pools of cholesterol in the body. To date, none of these determinants of cholesterol homeostasis have been quantitated in relation to either of the two forms of TPN or PPL management , either in patients in whom parenteral alimentation is a life-saving procedure or in individuals with an intact and fully functional gastrointestinal tract. It is our objective to determine what modifications in the TPN and PPL procedures cause a predictable net efflux of cholesterol from tissue stores, and to evaluate the therapeutic potential of both TPN and PPL for regression of the athrosclerotic process.
