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American Journal of Pathology, Vol 139, 101-113, Copyright © 1991 by American Society for Investigative Pathology

REGULAR ARTICLES

Lipid deposition and intimal stress and strain. A study in rats with aortic stenosis

T Zand, G Majno, JJ Nunnari, AH Hoffman, BJ Savilonis, B MacWilliams and I Joris
Department of Pathology, University of Massachusetts Medical School, Worcester 01655.

These experiments were designed to study the topography of lipid deposition in the stenotic aorta of hypercholesterolemic rats, and to correlate it with flow conditions and intimal stresses and strains studied in a scale biophysical model and in a computer model. A 69% +/- 5% stenosis was produced with a U-shaped metal clip. One month to 8 months later, the aorta was studied en face by light microscopy after fixation and lipid staining. The intima in the throat of the stenosis was almost completely free of lipid, whereas symmetric lipid deposits occurred as bands just above and especially just below the stenosis; elsewhere lipid deposits appeared to be random. The flow data obtained from the scale model showed that the intima in the throat of the stenosis was subjected to an increase of as much as 20 times in shear stress, whereas the lipid deposits just above and just below the stenosis were associated with asymmetric flow conditions: the proximal area corresponded to a region of rapidly increasing shear stress, the distal area to a region of low to normal shear stress and separated flow. A finite element computer model based on the aortic deformations indicated that the endothelium at the inlet and outlet of the stenosis is subjected to a symmetric pattern of elevated stresses and strains. These results indicate that 1) the pattern of lipid deposition can not be adequately explained by a hypothesis based solely on flow conditions, and 2) lipid deposits can develop in areas of increased fluid shear stress, decreased fluid shear stress, and increased intimal strains.

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