Contrasting Patterns of Spontaneous Aortic Disease in Young and Old Rabbits

Abstract

Abstract-The pattern of spontaneous lipid deposition around aortic branch ostia was mapped in New Zealand White rabbits aged 1 month or 2 to 6 years. The young rabbits were studied within 1 day of weaning, and the older rabbits had been maintained on a low-protein, low-fat diet. Plasma concentrations of total cholesterol for the two groups averaged 75 and 18 mg/dL, respectively. Aortas were fixed in situ at a pressure of 90 to 100 cm H 2 O, stained with oil red O, and photographed en face under an epifluorescence microscope. Areas of staining contrasted in color with the fixativestimulated autofluorescence of nondiseased tissue and were mapped by placing grids over the photomicrographs. Disease around intercostal ostia was rare, but two distributions were established by combining data from many branches. In weanlings, staining was seen within a triangular area downstream of the branch. In old animals, this area had the lowest frequency of disease; lesions tended to occur downstream of the spared region, along axes lying to either side of it, and at the lateral and upstream margins of the ostium. Disease was less rare at celiac branches. It occurred mainly downstream of the ostium in weanlings, whereas upstream sites were most affected in old animals, although significant disease remained at the juvenile locations. Earlier reports have described similar age-related distributions of disease in human aortas, consistent with a common underlying mechanism. The distributions also correlate with the spatial variations in arterial transport properties established in previous studies, and may be determined by them. (Arterioscler Thromb Vasc Biol. 1998;18:300-308.)

Two Patterns of Lipid Deposition in the Cholesterol-Fed Rabbit

“…Spontaneous disease in young and old rabbits fed the unsupplemented base diet from this supplier has been described in a previous report 5 and was not reassessed. The diet was administered over a period of 15 weeks, except that 1 rabbit from each group was killed after 13 weeks to monitor the progression of disease; these 2 animals did not differ in any significant way from the remainder of their respective groups, and data obtained from them are included in the analyses described below unless otherwise stated.…”

“…The animals were fed a diet (RABMA, Special Diet Services), described in detail elsewhere, 5 to which the manufacturer had added cholesterol (derived from sheep wool, Peboc) in soya oil. Spontaneous disease in young and old rabbits fed the unsupplemented base diet from this supplier has been described in a previous report 5 and was not reassessed.…”

“…[2][3][4] Similar changes in distribution with age are discernible in the rare, spontaneous disease affecting rabbits. 5 Of the many mechanical and biological attributes that vary around branches, corresponding age-related patterns have been demonstrated only for transport properties of the arterial wall. In juvenile rabbits, quasi-steady uptake of circulating macromolecules by the aortic wall is greater downstream of branches than upstream, 6 while the reverse pattern is observed in mature rabbits.…”

Use of a desktop scanner and spreadsheet software for mapping arterial disease

“…1996). Previous work (Barnes and Weinberg 1998) has shown that the precision of such visual estimates is acceptable. As in our earlier studies, the line spacing of the grid was equivalent to 120 µm before magnification.…”

“…Lipid deposits near rabbit aortic branches were mapped using the new scanner-based technique and, for comparison, with the photomicrographic technique used in previous studies (Barnes and Weinberg 1998Forster et al 1996;McGillicuddy et al 2001;Richards and Weinberg 2000). The rabbits were randomly selected from a large group fed a cholesterol-and L-arginine-enhanced diet as part of a trial examining the influence of L-arginine on experimental atherosclerosis (Weinberg and Cremers 2003).…”