Local delivery of paclitaxel using the double‐balloon perfusion catheter before stenting in the porcine coronary artery

Abstract

Paclitaxel is a new cancer chemotherapeutic agent that has been approved for clinical use in patients with a variety of different cancers. Paclitaxel inhibits cell proliferation by an action on microtubules. The aim of this study was to evaluate the safety and efficacy of locally delivered paclitaxel after coronary stent implantation. A novel double-balloon perfusion catheter was used to deliver the drug locally in the pig coronary artery. Twenty-seven domestic pigs underwent stent implantation of the left anterior descending artery. In the treatment group (n = 11), paclitaxel (10 ml; 10 micromol/l) was delivered using the double-balloon perfusion catheter prior to stent implantation. The control group received stent implantation only (n = 16). The animals were sacrificed 4 weeks later. Vessels were perfusion-fixed and morphometric analysis was performed using conventional techniques. In addition, the extent of injury was determined at each stent-strut area. Correlation of local injury and neointimal thickness was evaluated by linear regression. Neointimal thickness (paclitaxel 1.0 +/- 0.4 vs. control 0.7 +/- 0.3 mm), neointimal area (paclitaxel 4.1 +/- 2.2 vs. control 2.4 +/- 1.1 mm(2)), and the lumen area (paclitaxel 2.1 +/- 1.9 vs. control 2.5 +/- 0.9 mm(2)) did not show significant differences between both groups. Medial area (3.3 +/- 2.3 vs. 1.6 +/- 0.4 mm(2)) was larger in the vessels treated with paclitaxel (P < 0.05). Linear regression failed to show any difference in the response to injury between the two groups. Local delivery of paclitaxel with the double-balloon-perfusion catheter did not reduce neointima formation following stent implantation in native pig coronary arteries.

Paclitaxel coated balloons for coronary artery interventions: A comprehensive review of preclinical and clinical data

“…[22]. Furthermore, paclitaxel (locally applied by microporous balloons) prevented neointima formation in rabbits after balloon angioplasty, showing a significant histological reduction of intima area, wall thickness, and degree of stenosis in treated animals compared with controls [26,27].…”

7-Hexanoyltaxol–Eluting Stent for Prevention of Neointimal Growth

“…6 On the other hand, local delivery of paclitaxel with a double-balloon local infusion catheter (10 mL; 10 mol/L) failed to show any benefit after stenting in pig coronaries. 17 In the current study, which used a sleeve-based delivery system of 7-hexanoyltaxol, however, the favorable results of early human feasibility registries 8,9 have been well replicated, achieving a 70% reduction in neointimal hyperplasia compared with the control BMS. Moreover, qDES showed a higher correlation coefficient between postprocedural MSA and follow-up MLA than in BMS, indicating consistent efficacy of qDES, irrespective of various patient/lesion profiles and risk factors, and, therefore, variable degrees of biological activity in each lesion.…”

Nanotechnology in interventional cardiology

“…In an early study, local delivery of paclitaxel using a double‐balloon perfusion catheter and BMS implantation failed to show any difference compared with placebo in response to balloon injury in porcine coronary arteries 30. However, in a more recent study including some investigators of the aforementioned study, locally delivered paclitaxel showed marked reduction of neointimal proliferation and complete endothelialization 42 days after treatment in a porcine model 31.…”