Experimental atherosclerosis in rabbits was simulated by injecting the artificial fat emulsion Intralipid into the lumen of doubly-ligated rabbit carotid arteries. Sections of these arterial segments were studied with light and electron microscopy at periods from three to twenty days following ligation. When comparing the test vessel with the normal artery, the main alteration was an intimal thickening comprised of proliferating smooth muselc cells and fibroblasts. This hyperplasia was not prominent until the seventh day. The main change when comparing the test artery with a control, doubly-ligated one injected with Ringer solution was the accumulation of lipid droplets within all cells of the arterial wall. At earlier time-intervals these intracellular droplets were more electron-dense than the original Intralipid trigliceride particles, suggesting a metabolic transformation of the fatty acid moiety in the lipid to a more unsaturated form. The Intralipid particles close to the luminal surface of the endothelia were often much smaller than the original ones, suggesting their breakdown by a lipase; lipid might then be taken up by these cells in the form of free fatty acid, perhaps by vesicles forming rosette-shaped structures. Numerous ultrastructural changes following double-ligation, both with and without lipid, were demonstrated and compared to similar morphological changes in spontaneous and experimental atherosclerosis and in other model systems which combined arterial injury and hyperlipemia. We concluded that our results together with the numerous studies by other investigators suggest that injury to the arterial wall is the primary cause of arteriosclerosis and that lipid accumulation, although influencing the resulting morphology, is only secondary. In the past years a wealth of information has accumulated demonstrating that the reaction of the arterial wall to injury of various types is not only qualitatively similar to one another (Lorenzen, 1963; Waters, 1954), but resembles to a remarkable degree the non-lipid form of early spontaneous atherosclerosis (Schenk et al., 1966). The similarity between early lipid-containing atheroma and this injury-reaction is further enhanced when hyperlipemia is also induced concurrently with injury (Courtice and Schmidt-Diedrichs, 1962; Constantinides, 1968; Friedman and Byers, 1965; Still and Dennison, 1967; Kirkpatrick, 1967). Studies on doubly-ligated arterial segments, in particular, have been used by a number of investigators (Buck, 1961; Hackensellner et al., 1965; Friedman et al., 1966) as a model for studies on experimental atherosclerosis. Recently Friedman et al. (1966) combined the hypoxic and mechanical irritation of double ligation of carotid artery segments in rabbits with hyperlipemia. The latter was simulated by injecting suspensions of rat thoracic lymph chylomicrons into the lumen of the doubly-ligated segment. Light microscopic observations of the vessel wall were then made. Friedman et al. (1966) were mainly concerned with the genesis of foam cells which they suggested were derived from endothelial cells. If this model system were to be combined with an electron microscopy study, not only could more information be possibly obtained on foam cell genesis, but ultrastructural similarities with spontaneous and diet-induced atherosclerosis could also be ascertained, as could some details on lipid uptake by arterial cells. The right common carotid artery of rabbits was therefore doubly-ligated and the lumen filled with an artificial fat emulsion. The segments were then studied at various periods of up to twenty days following ligation both with the light and electron microscope. © 1972 Springer-Verlag.
