The Kinetics of Microcirculatory Dysfunction During Paclitaxel Application in an In Vivo Mouse Model

TL;DR

This study shows that paclitaxel chemotherapy causes immediate and lasting microcirculatory issues in mice, suggesting early and prolonged interventions may help prevent nerve damage.

Contribution

The study is the first to systematically track the timing of paclitaxel-induced microcirculatory dysfunction in a mouse model.

Findings

Paclitaxel caused immediate and lasting microcirculatory disturbances in mice.

Functional capillary density decreased, and venous leukocyte adhesion and endothelial permeability increased.

These effects persisted for at least three hours after paclitaxel administration.

Abstract

Objective: Chemotherapy-induced peripheral neuropathy often has a lasting impact on the quality of life without existing causal treatment options. The aim of this study was to systematically investigate the temporal occurrence of paclitaxel-induced peripheral microcirculatory dysfunction. Methods: Thirty-one female SKH-1 mice received six cycles of paclitaxel intraperitoneally in the treatment group and six cycles of saline in the control group. Intravital fluorescence analyses were performed in the groups 180 min after saline administration and immediately, 60 min, 120 min, and 180 min after paclitaxel administration to evaluate the effects on microcirculation and inflammation. Results: In addition to signs of systemic inflammation, the intravital microscopy revealed a marked reduction in functional capillary density, increased venous leukocyte adhesion, and endothelial permeability that persisted for at least three hours in paclitaxel-treated mice. Conclusions: Our results show that paclitaxel-induced microcirculatory disturbances manifest immediately after application and last at least for 3 h. This suggests that options for prevention or at least amelioration could potentially be most effective if initiated parallel to the induction of chemotherapy and continued for a prolonged period of at least 3 h. Whether and to what extent the prolongation of the preventive strategies influences CIPN in the long term needs to be studied further.

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