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Cardiovascular Research 1997 36(3):396-407; doi:10.1016/S0008-6363(97)00168-5
© 1997 by European Society of Cardiology
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Copyright © 1997, European Society of Cardiology

Predictors of luminal narrowing by neointima after angioplasty in atherosclerotic rabbits

S.David Gertza,*, William L Barryb, Lawrence W Gimpleb, Shmuel Banaia,c, Louise S Pereza, Coleen A McNamarab, Eric R Powersb, Michael Ragostab, Gary K Owensb, William C Robertsd and Ian J Sarembockb

aDepartment of Anatomy and Cell Biology, The Hebrew University-Hadassah Medical School, POB 12272, Jerusalem 91120, Israel
bThe Cardiovascular Division, University of Virginia, Charlottesville, VA, USA
cDepartment of Cardiology, Bikur Cholim Hospital, Jerusalem, Israel
dBaylor Cardiovascular Institute, Baylor University Medical Center, Dallas, TX, USA

* Corresponding author. Tel. (+972-2) 675-8446, -8422; Fax (+972-2) 675-7451, E-mail: gertz@yam-suff.cc.huji.ac.il

Objective: The present study was designed to identify the predictors of cross-sectional area narrowing by neointima (%CSAN-N) after balloon angioplasty (BA) in the cholesterol fed rabbit model. Methods: Angiographic, histomorphometric, and immunohistochemical data were analyzed from 91 femoral arteries of New Zealand white rabbits. Focal atherosclerosis was induced by air desiccation of the endothelium followed by a 2% cholesterol diet for 28 days. The rabbits received heparin (150 U/kg) at the time of BA (2.5 mm; three, 60-second, 10-atm inflations). Arteries were perfusion-fixed and excised 7 (n = 16), 14 (n = 11), 21 (n = 9), or 28 (n = 20) days after BA. Non-angioplastied arteries were de-endothelialized (cholesterol-fed [n = 12] or normal diet [n = 8]), non-injured but cholesterol-fed (n = 7), or normal (n = 8). Results: Univariate regression across all groups showed that the absolute area of the lumen by histomorphometry (LA) correlated significantly with the area bounded by the external elastic lamina (EEL) (vessel size), but no correlation was found with the absolute area of neointima or media, the percentage disruption of the internal elastic lamina (IEL), or the percentage of neointima and media occupied by foam cells. However, %CSAN-N correlated significantly with the area bounded by the EEL, significantly with the absolute neointimal area, and negatively with the absolute LA (p<0.0001). Significant correlations were also found between %CSAN-N and the % IEL disrupted, the area of neointima and media occupied by RAM-11+ foam cells, and the loss of {alpha}-actin positivity in the media (p<0.0001). Conclusions: These studies show that neointimal formation contributes significantly to luminal narrowing 1 month after angioplasty in this model, that the degree of vascular injury and the extent of foam cell accumulation in the neointima and media are significant independent predictors of neointimal formation, and that the area of the neointima, and the percent narrowing by neointima, are important predictors of remodeling itself (EEL area). These predictors were not identifiable when the analysis was focused on the determinants of absolute luminal area alone.

KEYWORDS Angioplasty; Neointima; Restenosis; Remodeling; New Zealand white rabbits


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