Percutaneous transluminal coronary angioplasty is an accepted treatment for
coronary artery disease. The major limitation, however, is the high incidence of restenosis which limits the long-term benefit of this intervention.
Paclitaxel is a new antiproliferative agent that has generated considerable scientific interest since it was introduced in clinical trials in the early 1980s. Recent in vitro studies have shown that
paclitaxel has considerable antiproliferative activity in human coculture systems. In the present study the efficacy of
paclitaxel was investigated after development of an intimal plaque by electrical stimulation and additional
cholesterol diet and subsequent balloon angioplasty in 63 New Zealand White rabbits. Local
drug delivery of
paclitaxel was accomplished in 30 rabbits with a porous balloon
catheter (35 holes, hole diameter 75 microm, 2.5 mm
catheter diameter).
Paclitaxel was administered locally with 4 ml (
solution 10(-5) mol/L) using an injection pressure of 2 atm. To study the extent of restenosis and morphological changes, the animals were sacrificed 7, 28 or 56 days after intervention. After staining procedures quantification of SMC proliferation, intimal macrophages and morphological analyses were performed.
Paclitaxel plasma concentrations were measured using HPLC technique. One week after balloon angioplasty the arteries treated with local
paclitaxel delivery showed an insignificant trend towards a reduction in intimal smooth muscle cell proliferation (untreated 8.4 +/- 4.9 % vs
paclitaxel treated 2.4 +/- 2.4 %, p = NS). However, this resulted in a significant reduction of
stenosis degree of 66 % 8 weeks after intervention compared to the untreated group (untreated 41 +/- 18 % vs
paclitaxel treated 14 +/- 11 %, p = 0.005). In conclusion, locally delivered
paclitaxel prevented neointimal thickening in the rabbit carotid artery after balloon angioplasty. Local
paclitaxel treatment may therefore be a clinical option for the prevention of restenosis after coronary interventions. However, further preclinical studies have to prove long-term efficacy and safety.