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Updated: Aug 4, 2026
Chemotherapy-induced Vascular Toxicity - Real-time In vivo Imaging of Vessel Impairment
Published on: January 7, 2015
Visualization and comparison of drug effects after local paclitaxel delivery with different catheter types
C Herdeg1, M Oberhoff, A Baumbach
1Dept. of Medicine, University of Tuebingen, Germany. christian.herdeg@t-online.de
Background:
The microtubule stabilizing compound paclitaxel has proved to have potent antiproliferative effects on smooth muscle cells both in vitro and in vivo. It induces cellular modifications that result in reduced proliferation, migration and signal transduction by shifting the cellular microtubule equilibrium towards assembly. We therefore reasoned that a visualization of the altered cytoskeleton could enable an evaluation of the drug effects following local drug delivery.
Methods And Results:
3 catheters - the porous balloon, the microporous balloon and the double balloon catheter - were chosen for this study representing the spectrum from passive to active, pressure-driven delivery. After the induction of a defined plaque in the right carotid arteries of 40 New Zealand rabbits by electrical stimulation, 32 animals underwent balloon dilatation and 8 animals served as pre-interventional control group with electrostimulation only. In 24 animals (n = 8 in each group) subsequent local paclitaxel delivery (10 micromol/L) was performed. 8 animals served as control with angioplasty only. Vessels were excised 1 week following intervention. Immunohistochemistry with antibodies against bromodeoxyuridine, alpha-actin, macrophages, von Willebrand factor and alpha-tubulin was performed. Cytoskeletal changes were analyzed by electron microscopy. Tubulin staining and electron microscopy revealed changes with distinct staining patterns for the different catheters. Specific catheter-induced injuries could be identified for the porous and double balloon catheter. Intimal proliferation, percentage of macrophages and extent of injury favor the double balloon catheter for local paclitaxel delivery.
Conclusions:
The alterations of the cytoskeleton induced by paclitaxel allowed for the detection of drug action by staining of tubulin and electron microscopy. This enables an evaluation of transfer, distribution and drug effects directly in the vasculature without marker substances. The double balloon catheter appears to be best suited for local paclitaxel therapy.
Insights
Paclitaxel alters cytoskeleton, enabling visualization of its effects after local delivery. The double balloon catheter is most effective for delivering paclitaxel to treat vascular smooth muscle cell proliferation.
Area of Science:
- Vascular biology
- Pharmacology
- Medical devices
Background:
- Paclitaxel (PTX) is a microtubule-stabilizing agent with potent antiproliferative effects on vascular smooth muscle cells.
- PTX induces cytoskeletal modifications, reducing cell proliferation, migration, and signal transduction by promoting microtubule assembly.
- Visualizing these drug-induced cytoskeletal alterations could allow for direct evaluation of local drug delivery efficacy.
Purpose of the Study:
- To assess the efficacy of different balloon catheter designs for local paclitaxel delivery.
- To visualize paclitaxel's effects on the vasculature by analyzing cytoskeletal changes.
- To determine the optimal catheter for local paclitaxel therapy.
Main Methods:
- Three catheter types (porous balloon, microporous balloon, double balloon) were evaluated for local paclitaxel delivery in a rabbit carotid artery model.
- Vascular injury was induced by electrical stimulation, followed by balloon angioplasty and paclitaxel administration (10 micromol/L) in selected groups.
- Immunohistochemistry and electron microscopy were used to analyze cytoskeletal changes (tubulin), intimal proliferation, macrophage infiltration, and catheter-induced injury.
Main Results:
- Distinct tubulin staining patterns and cytoskeletal changes were observed, varying with catheter type.
- The porous and double balloon catheters caused identifiable, specific injuries.
- The double balloon catheter demonstrated favorable outcomes regarding intimal proliferation, macrophage presence, and injury extent.
Conclusions:
- Paclitaxel-induced cytoskeletal alterations are detectable via tubulin staining and electron microscopy, enabling direct assessment of drug effects in the vasculature.
- This method allows evaluation of drug transfer, distribution, and efficacy without requiring additional marker substances.
- The double balloon catheter is the most suitable device for local paclitaxel delivery in this model.
