lipofundin-s and Arteriosclerosis

We have shown previously that parenterally-administered lipid emulsions can be utilized to induce early atherosclerosis in the aortas of Sprague-Dawley rats. In order to evaluate the effect of obesity on lipid-induced atherogenesis, we have utilized this same approach in the present study to demonstrate that i.v. infusions of the parenteral lipid emulsion, Lipofundin-S, will induce in the genetically obese Zucker rat and its lean littermate aortic endothelial and myofibroelastic changes indicative of early atherogenesis. Four groups of rats were used: 1) obese controls, 2) obese lipid-infused, 3) lean littermate controls, and 4) lean littermate lipid-infused. Observations were made with light and transmission electron microscopy (TEM), using qualitative morphological criteria to evaluate the results. Based on the fact that both untreated control and Lipofundin-S-induced atherosclerosis was more frequent and generally more advanced in the obese animals than in their respective lean counterparts, it appears that the obese Zucker rat is more susceptible to both spontaneous and hyperlipidemia-induced atherosclerosis than its respective lean littermate. Thus, obesity in these animals, as might be the case in humans, could potentiate an atherogenic process already enhanced by hyperlipidemia.

Topics: Animals; Arteriosclerosis; Disease Models, Animal; Drug Combinations; Emulsions; Glycerol; Infusions, Parenteral; Male; Obesity; Phospholipids; Rats; Rats, Zucker; Reference Values; Risk Factors; Soybean Oil

This study shows that arterial smooth muscle cells (SMC) isolated from rats receiving atherogenic doses of the lipid emulsion, Lipofundin-S, alter their in vitro growth properties. Compared to cells from control animals, SMC isolated from Lipofundin-S-infused rats show a reduction in both saturation density and response to increasing serum concentrations, without a change in the baseline proliferation. Also, SMC isolated from lipid-treated animals and grown for five days in the presence of 30, 150, or 300 pg/ml estradiol show a 30% increase in growth vs. cells from controls. Epinephrine at 1 microM stimulates growth in SMC from control rats, while causing no growth enhancement over five days in cells from lipid-infused animals. Thus, atherogenic infusions of Lipofundin-S into rats cause phenotypic changes in arterial SMC which can be passed to successive cell generations in vitro.

Topics: Animals; Aorta, Thoracic; Arteriosclerosis; Blood Physiological Phenomena; Cell Division; Cells, Cultured; Drug Combinations; Epinephrine; Estradiol; Fat Emulsions, Intravenous; Glycerol; Male; Muscle, Smooth, Vascular; Phospholipids; Rats; Rats, Inbred Strains; Soybean Oil; Triglycerides

30 rats were divided into 3 experimental groups. These included 8 days of Lipofundin treatment + 8 days recovery period (Group I), 16 days of Lipofundin treatment (Group II), and 16 days of Lipofundin treatment + 8 days recovery period (Group III). After sacrifice semi-thin and ultra-thin sections prepared from the aorta segments were examined light and electron microscopically. In addition to the development of alterations characteristic of the Lipofundin-model, the accumulation of collagen fibres was also observed. After 16 days of Lipofundin treatment the alterations were much more advanced than after 8-day treatment. Subsequent migration of smooth muscle cells through the newly formed internal elastic lamina was apparent and led to thickening of the sclerotic plaque. When the 16-day Lipofundin treatment was followed by a recovery period of 8 days prior to sacrifice, no signs of regression were seen. The alterations were present in unchanged form and the only difference was in the extent of accumulation of collagen fibres.

Topics: Animals; Aorta; Arteriosclerosis; Disease Models, Animal; Drug Combinations; Fat Emulsions, Intravenous; Glycerol; Male; Microscopy, Electron; Phospholipids; Plant Oils; Rats; Rats, Inbred Strains; Soybean Oil

The present study is the first work to evaluate thrombin-, ADP-, and collagen-induced platelet aggregation in laboratory rats receiving alimentation with the parenterally-administered lipid emulsion, Lipofundin-S, in doses sufficient to induce early atherosclerotic changes in the aorta. The aggregometry parameters of percent maximum aggregation, slope, and b2 or b20 almost uniformly indicate that such lipid treatments result in a statistically significant increased sensitivity of the platelets to ADP and collagen, while no change is noted with thrombin as the aggregating agent. By varying the amounts of ADP and collagen during aggregometry, we also demonstrate that the concentrations of these reagents necessary for equivalent platelet aggregation is substantially lower in lipid-infused rats than in controls. We conclude from this study that such lipid infusions can cause increased platelet aggregation, and that these lipids probably act in a synergistic fashion by affecting a variety of components which comprise the atherogenic process and its clinical endpoint. In addition, we believe that this experimental approach is of interest in that infusions of clinically-useful lipid emulsions are easily controlled, while alterations in platelet physiology and aortic structure occur concurrently and rapidly.

Topics: Adenosine Diphosphate; Animals; Arteriosclerosis; Blood Platelets; Collagen; Drug Combinations; Emulsions; Glycerol; Infusions, Parenteral; Lipids; Male; Phospholipids; Platelet Aggregation; Rats; Rats, Inbred Strains; Soybean Oil; Thrombin

It has been demonstrated by us and other workers that rats receiving I.V. infusions of Lipofundin-S will develop aortic changes indicative of early atherosclerosis. However, different lipid emulsions which are used in the clinical setting for parenteral nutrition vary substantially in chylomicron size and fatty acid composition. Therefore, in an attempt to better understand the mechanism by which a lipid emulsion might induce vessel lesions, we compared the nature of potential aortic changes resulting from infusions of Liposyn, Intralipid, or Lipofundin-S into the tail veins of Sprague-Dawley rats. Three groups of animals received either Liposyn (N = 10), Intralipid (N = 5), or Lipofundin-S (N = 9) at the rate of 6 g fat/kg body wt/day for 10 consecutive days. A fourth group (N = 5) received saline in equivalent dose to evaluate the effect of injection volume on vessel lesion formation. The other controls (N = 6) received no injections. Rats were sacrificed 24 hrs after the last infusion, and 1 mm rings from the top of the aortic arch and proximal third of the thoracic aorta were prepared for transmission electron microscopy (TEM). Examination by TEM allows two main conclusions to be drawn for both segments of the aorta. First, all three emulsions are capable of inducing early vessel changes which include endothelial damage, platelet adherence to damaged endothelium or subendothelial collagen, intimal phagocytic cells, and intimal smooth muscle cells surrounded by collagen bundles and elastin plates. Saline-infused rats only show occasional subendothelial swelling. None of the above-described changes are seen in any of the uninjected controls. Second, Lipofundin-S induces smooth muscle penetration of the intima in 7 of 9 rats, while Liposyn causes such changes in 2 of 10 animals. This difference in the efficiency with which the two emulsions induce the most advanced changes is statistically significantly by Chi Square (p less than 0.05). Intralipid produces smooth muscle penetration of the intima in 2 of 5 rats. The composition of the three emulsions suggests that the lower percent of linoleic acid and larger chylomicron size in Lipofundin-S may account for these differences, at least in part.

Topics: Animals; Aorta; Arteriosclerosis; Chylomicrons; Drug Combinations; Emulsions; Endothelium, Vascular; Fat Emulsions, Intravenous; Fatty Acids; Glycerol; Lecithins; Muscle, Smooth, Vascular; Phospholipids; Rats; Rats, Inbred Strains; Safflower Oil; Soybean Oil; Time Factors

Intravenous administration of Lipofundin-S oil, in the rat induces arteriosclerotic lesions within several days. Changes in lipids and lipoproteins were studied by lipid electrophoresis, ultracentrifugation and gel filtration. One hour after injection of Lipofundin, a dramatic increase occurred in triglycerides and phospholipids, reflecting the composition of the lipid emulsion. During a period of 6-7 h the lipid concentrations normalized by hydrolysis. Repeated injections (every 12 h) of Lipofundin-S led to persisting changes in the lipoprotein concentrations within 2-4 days. Very-low-density and high-density lipoprotein (alpha-lipoprotein) levels decreased, whereas low-density lipoprotein (beta-lipoprotein) levels increased. The beta-/alpha-lipoprotein ratio, as determined from the peak areas of the lipoprotein electrophoresis pattern, increased significantly. The alterations of this 'atherogenic index' may cause the atherosclerotic lesions observed in the aorta of animals which are normally resistant to atherosclerosis.

Topics: Animals; Aorta; Arteriosclerosis; Drug Combinations; Glycerol; Histocytochemistry; Injections, Intravenous; Lipids; Lipoproteins; Male; Microscopy, Electron; Phospholipids; Plant Oils; Rats; Rats, Inbred Strains; Soybean Oil; Time Factors

Topics: Animals; Aorta; Arteriosclerosis; Disease Models, Animal; Drug Combinations; Glycerol; Lymphatic System; Microscopy, Electron; Oils; Phospholipids; Rats; Rats, Inbred Strains; Soybean Oil

Topics: Animals; Arteries; Arteriosclerosis; Disease Models, Animal; Drug Combinations; Glycerol; Microscopy, Electron; Microtomy; Muscle, Smooth; Oils; Phospholipids; Rats; Rats, Inbred Strains; Soybean Oil

Topics: Animals; Arteries; Arteriosclerosis; Disease Models, Animal; Drug Combinations; Glycerol; Microscopy, Electron, Scanning; Microtomy; Oils; Phospholipids; Rabbits; Soybean Oil