Sevoflurane preconditioning protects from posttransplant injury in mouse lung transplantation

Yamada, Yoshito; Laube, I; Jang, Jae–Hwi; Bonvini, John M.; İnci, İlhan; Weder, Walter; Schimmer, Beatrice Beck; Jungraithmayr, Wolfgang

doi:10.1016/j.jss.2017.03.021

Cited by 10 publications

(4 citation statements)

References 31 publications

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“…Unfortunately, these results did not reach statistical significance. This is in accordance with previously reported findings that an attenuation of AR does not necessarily have an impact on the functionality of the transplanted organ on postoperative day 5 in this particular model [16]. However, the occurrence of AR has been linked to the development of chronic rejection, which is known to be one of the most important life-limiting factors after lung transplantation [3,23,24].…”

Section: Discussionsupporting

confidence: 92%

“…Naidu and colleagues previously demonstrated that TNF-α release from pulmonary macrophages 4 h after reperfusion might be critical for the development of lung I/R injury [15]. Therefore, the reduced plasma levels of TNF-α found in the ropivacaine animals 3 h after transplantation in the current study support the hypothesis that ropivacaine might be able to blunt I/R injury occurring during the process of transplantation and subsequently preserve endothelial barrier function [4,16,17].…”

Section: Discussionsupporting

confidence: 80%

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

Maeyashiki

Jang

Janker

et al. 2019

Lung

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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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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 80%

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

Maeyashiki

Jang

Janker

et al. 2019

Lung

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“…LDH and TNF-α levels, however, showed no significant between-group difference. Various studies have shown that sevoflurane attenuates pulmonary IRI and inflammation [17][18][19][20]. In a rat EVLP model, Wang et al [21] showed that adding sevoflurane directly to the perfusion system upon the start of EVLP was associated with reduced levels of IRI injury markers like TNF-α and LDH.…”

Section: Discussionmentioning

confidence: 99%

“…Volatile anesthetic agents, like sevoflurane, have been shown to reduce IRI in various organs [12][13][14][15][16], including the lungs [17][18][19][20][21], in animals and in humans. The use of sevoflurane may protect organs against IRI by preventing mitochondrial permeability transition pores from opening, preserving the glycocalyx, upregulating and stabilizing hypoxic inducible factors (HIFs) and directly affecting circulating immune cells [22][23][24][25][26][27][28][29].…”

Section: Introductionmentioning

confidence: 99%

Ex Vivo Optimization of Donor Lungs with Inhaled Sevoflurane during Normothermic Ex Vivo Lung Perfusion (VITALISE): A Pilot and Feasibility Study in Sheep

Steinkühler,

Yang,

et al. 2024

IJMS

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Volatile anesthetics have been shown in different studies to reduce ischemia reperfusion injury (IRI). Ex vivo lung perfusion (EVLP) facilitates graft evaluation, extends preservation time and potentially enables injury repair and improvement of lung quality. We hypothesized that ventilating lungs with sevoflurane during EVLP would reduce lung injury and improve lung function. We performed a pilot study to test this hypothesis in a slaughterhouse sheep DCD model. Lungs were harvested, flushed and stored on ice for 3 h, after which EVLP was performed for 4 h. Lungs were ventilated with either an FiO2 of 0.4 (EVLP, n = 5) or FiO2 of 0.4 plus sevoflurane at a 2% end-tidal concentration (Cet) (S-EVLP, n = 5). Perfusate, tissue samples and functional measurements were collected and analyzed. A steady state of the target Cet sevoflurane was reached with measurable concentrations in perfusate. Lungs in the S-EVLP group showed significantly better dynamic lung compliance than those in the EVLP group (p = 0.003). Oxygenation capacity was not different in treated lungs for delta partial oxygen pressure (PO2; +3.8 (−4.9/11.1) vs. −11.7 (−12.0/−3.2) kPa, p = 0.151), but there was a trend of a better PO2/FiO2 ratio (p = 0.054). Perfusate ASAT levels in S-EVLP were significantly reduced compared to the control group (198.1 ± 93.66 vs. 223.9 ± 105.7 IU/L, p = 0.02). We conclude that ventilating lungs with sevoflurane during EVLP is feasible and could be useful to improve graft function.

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Lung Transplantation

Spellman¹,

Sutherland²

2022

Cohen's Comprehensive Thoracic Anesthesia

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Sevoflurane preconditioning protects from posttransplant injury in mouse lung transplantation

Cited by 10 publications

References 31 publications

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

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

Ex Vivo Optimization of Donor Lungs with Inhaled Sevoflurane during Normothermic Ex Vivo Lung Perfusion (VITALISE): A Pilot and Feasibility Study in Sheep

Lung Transplantation

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