Effects of pactitaxel on neointimal proliferation and remodeling in the rabbit carotid artery: A mathematical model of analysing the results

Paclitaxel, the active ingredient in Taxol(R), is a potent antiproliferative substance, which leads to reduced cellular proliferation, migration and signal transduction via alteration of the cytoskeleton. Paclitaxel has attracted a lot of interest in interventional cardiology, and the recent data obtained with paclitaxel-eluting stents are excellent. In a large animal study with New-Zealand rabbits we recently could show that local paclitaxel delivery leads to a significant inhibition of neointimal proliferation as well as to a significant increase of the total vessel area. Vasocontractile function after paclitaxel treatment also showed major impairment. These data and the mode of action of paclitaxel make it likely that paclitaxel also has strong effects on vascular remodeling. Therefore we performed a new morphometric analysis of the data of our animal-study. 66 New Zealand rabbits were included in the study. A local paclitaxel delivery (10 ml, 10 muM) was performed, using the double-balloon catheter. Preinterventional animals and solely balloon-dilated rabbits served as controls. Vessels were excised I week, I month and 2 months after intervention. Histological sections (4 pm) were stained with different antibodies and analyzed morphologically. Quantitative analysis was performed using computerized morphometry. In order to investigate the effects of paclitaxel on remodeling we sought for a way to combine the data of thousands of histological sections for an overview of vessel geometry. A mathematical model was developed that allows for reconstruction and graphic display of different layers of the vessel wall. The mathematical model and the results of the measurements with this model are presented in this paper.