Intrapericardial paclitaxel delivery inhibits neointimal proliferation andpromotes arterial enlargement after porcine coronary overstretch

Background-Catheter-based intrapericardial (IPC) delivery of therapeutic ag ents has recently been demonstrated. Paclitaxel is known to inhibit vascula r smooth muscle cell proliferation. This study examined the effect of LPC i nstillation of paclitaxel on neointimal proliferation after balloon overstr etch of porcine coronary arteries. Methods and Results-Overstretch injury of coronary arteries was followed by LPC administration of micellar paclitaxel at low dose (LD, 10 mg; n=6) or high dose (HD, 50 mg; n=7) or of control micelles (50 mg, n=5). Animals wer e euthanized 28 days after balloon dilation. Arterial injury indices were n o different among the groups. The neointimal area, maximal intimal thicknes s, and adventitial thickness were significantly reduced in both LD (0.47 +/ - 0.04 mm(2), 0.43 +/- 0.03 mm, and 0.35 +/- 0.02 mm, respectively) and HD (0.51 +/- 0.06 mm(2), 0.42 +/- 0.03 mm, and 0.38 +/- 0.03 mm, respectively) paclitaxel groups compared with the control group (0.79 +/- 0.07 mm(2), 0. 56 +/- 0.02 mm, and 0.47 +/- 0.02 mm, respectively; P<0.001). Meanwhile, th e vessel circumference measured at the external elastic lamina of paclitaxe l-treated vessels was significantly larger than the control circumference. Apoptotic cells were found in the neointima. The apoptotic cell percentage was not different between the control (1.72%) and LD (2.31%) groups but was higher in the HD group (7.07%, P<0.0001 versus control and LD groups). Imm unostaining for matrix metalloproteinase-2 revealed concurrent reduction in the HD group compared with the control and LD groups. Conclusions-IPC space delivery of a single dose of paclitaxel significantly reduces vessel narrowing in this balloon-overstretch model. This effect is mediated by reduction of neointimal mass as well as positive vascular remo deling.