A noninjury, diet-induced swine model of atherosclerosis for cardiovascular-interventional research.

Abstract

To investigate whether atherosclerotic vascular disease in the microswine model can be induced by atherogenic diet alone and does not require balloon injury or endothelial denudation as widely stated in the literature, 28 female Yucatan microswine were fed a high-fat, high-cholesterol diet, including 2% sodium cholate, for an average of 310 +/- 13 days. Four control swine were placed on a regular diet for an average of 287.2 +/- 7.8 days. Selective coronary arteriography and morphologic and histologic studies were performed at the end of this period. Coronary arteries were fixed in vivo by pressure perfusion of formalin. Angiograms and sequential histologic sections were reviewed by a double-blind team. The angiography did not show apparent disease in all vessels but generally revealed mild irregularity. Quantitatively, there was a 30.5 +/- 3.5% stenosis (mean +/- standard error, P < 0.05 vs. control) in left anterior descending (LAD), 40.7 +/- 4.5% of stenosis in right coronary artery (RCA) (P < 0.01 vs. control), and 24.8 +/- 3.7% of stenosis in left circumflex artery (LCX). The lesions were eccentric in 95% of LCA, 95.8% of RCA, and 75% of LCX, and the remainder were concentric lesions. Typical lesions were characterized by significant intimal proliferation, cholesterol clefts, necrotic cores, heavy extracellular fat deposition, and calcification. Control animals had only occasional, minimal intimal lipid deposition in coronary arteries. These findings suggest that the Yucatan microswine is an ideal coronary atherosclerosis animal model for vascular research. Lesions can be induced by atherogenic diet alone. Cholesterol uptake is increased by adding sodium cholate to the feed. Moreover, balloon injury of the intima or media is not required to induce significant atherosclerotic lesions in coronary arteries.