Abstract
Preliminary studies in 400 New Zealand albino rabbits produced a reliable animal model of nutrient-induced atherosclerosis that simulated that observed in humans. Atherosclerosis was then induced in an additional 1600 rabbits in sets of 40 animals each, maintaining plasma cholesterol concentrations between 1000 and 2000 mg/dL for 6-20 weeks. In each set, 10 control rabbits were killed to document baseline atherosclerosis, and the other 30 rabbits were assigned randomly to one of three groups of 10 rabbits. Groups of 10 rabbits were either continued on the atherogenic diet (group I), given standard laboratory rabbit pellets (group II), or infused continuously with specially formulated anticholesterol solutions via central venous catheters (group III) for 6 weeks. At autopsy, atherosclerotic lesions consistently involved 85-95% of the aorta in group I. In group II, atherosclerosis was comparable with the baseline control group with no regression. In group III, regression of atherosclerosis by 90-95% was consistently documented. Correlations between plasma amino acids and plasma cholesterol concentrations were established in four humans with severe atherosclerosis to maximize the cholesterol reduction capacity of the amino acid formulation. Infusion of the modified total parenteral nutrition solution induced prompt reduction in plasma cholesterol levels by 40-60% regardless of the initial level and was accompanied by evidence of regression of atherosclerosis after a 90-day infusion therapy period.