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Published in: Lung 2/2019

01-04-2019 | Anesthetics | Acute Lung Injury

The Amide Local Anesthetic Ropivacaine Attenuates Acute Rejection After Allogeneic Mouse Lung Transplantation

Authors: Tatsuo Maeyashiki, Jae-Hwi Jang, Florian Janker, Yoshito Yamada, Ilhan Inci, Walter Weder, Tobias Piegeler, Wolfgang Jungraithmayr

Published in: Lung | Issue 2/2019

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Abstract

Purpose

Acute allograft rejection after lung transplantation remains an unsolved hurdle. The pathogenesis includes an inflammatory response during and after transplantation. Ropivacaine, an amide-linked local anesthetic, has been shown to attenuate lung injury due to its anti-inflammatory effects. We hypothesized that the drug would also be able to attenuate acute rejection (AR) after allogeneic lung transplantation.

Methods

Allogeneic, orthotopic, single left lung transplantation was performed between BALB/c (donors) and C57BL/6 (recipients) mice. Prior to explantation, lungs were flushed with normal saline with or without ropivacaine (final concentration 1 µM). Plasma levels of tumor necrosis factor-α and interleukins − 6 and − 10 were measured 3 h after transplantation by ELISA. Lung function was assessed on postoperative day five and transplanted lungs were analyzed using histology (AR), immunohistochemistry (infiltrating leukocytes) and Western blot (phosphorylation and expression of Src and caveolin-1).

Results

Ropivacaine pre-treatment significantly reduced AR scores (median 3 [minimum–maximum 2–4] for control vs. 2 [1–2] for ropivacaine, p < 0.001) and plasma levels of tumor necrosis factor-α (p = 0.01) compared to control, whereas plasma concentrations of interleukin − 6 (p = 0.008) and − 10 (p < 0.001) were increased by ropivacaine. The number of T-lymphocytes infiltrating the transplanted lung was attenuated (p = 0.02), while no differences in macrophage or B-lymphocyte numbers could be observed after ropivacaine pre-treatment. Caveolin-1 phosphorylation in ropivacaine-treated lungs was diminished (p = 0.004).

Conclusions

Pre-treatment of donor lungs with the local anesthetic ropivacaine diminished histological signs of AR after orthotopic left lung transplantation in mice, most likely due to reduced infiltration of T-lymphocytes into the graft.
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Metadata
Title
The Amide Local Anesthetic Ropivacaine Attenuates Acute Rejection After Allogeneic Mouse Lung Transplantation
Authors
Tatsuo Maeyashiki
Jae-Hwi Jang
Florian Janker
Yoshito Yamada
Ilhan Inci
Walter Weder
Tobias Piegeler
Wolfgang Jungraithmayr
Publication date
01-04-2019
Publisher
Springer US
Published in
Lung / Issue 2/2019
Print ISSN: 0341-2040
Electronic ISSN: 1432-1750
DOI
https://doi.org/10.1007/s00408-019-00197-5

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