P170Comparison of atherogenic porcine and rabbit models in restenosis studies

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Abstract

Background

Animal models are needed to preclinically evaluate in-stent restenosis (ISR) reducing therapies. Currently used models vary in large measure between different research groups and separate studies. Our aim was to compare lesion characteristics and feasibility of the models for ISR studies.

Methods

We compared experimental atherosclerotic lesions in landrace porcine coronary arteries (n = 33) and rabbit aortas (n = 12) by combining endothelial injury by balloon dilation with high serum lipid levels. Dyslipidemia was diet induced, except for WHHL rabbits which have naturally high serum cholesterol levels.

Results

Rabbit aortas developed uniform lesions rich in lipids (Fig. A). Due to different anatomy of the arteries, porcine coronary artery denudation and balloon over dilatation lesions (Fig. B) had high variation in size and structure inside the groups. Porcine coronary stenosis differed from 25 to 70 % compared to WHHL stenosis of 55.1 to 85.1%. The porcine coronary lesions had more connective tissue and SMCs than lesions in rabbit aorta. Landrace porcine did not develop high serum lipid levels with feasible lipid diets. Serum cholesterol levels were 4.2 + /- 1.2 mmol/L in porcine high lipid diet group compared to 18.7 + /- 4.6 mmol/L in NZW lipid diet group and 17.3 + /- 1.3 mmol/L in WHHL group.

Conclusions

The variation in the degree of stenosis and lesion characteristics was high within the porcine denudation groups. We suggest the atherogenic rabbit aorta models lipid and inflammatory profile of atherosclerotic human coronary better than the atherogenic porcine model. Intact porcine coronary is more comparable to human coronaries for its structure and heamodynamics. Hence it can be used to assess restenosis unaffected by atherosclerosis.

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