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      Vagal electrostimulation in postoperative thoracic surgery reduces the systemic inflammatory response and cardiopulmonary complications: an experimental study in pigs

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          Abstract

          Background

          Conventional thoracotomy (CT) often leads to systemic inflammatory response syndrome (SIRS), which induces several clinical complications. CT remains widely used in low-income institutions. Although minimally invasive surgical procedures, such as robotic surgery (RS), have been used to prevent many of the complications inherit from the surgical procedure. Here, we investigated the protective effect of vagus nerve stimulation (VNS) in a pre-clinical model during CT or RS and postoperative period (POP) relative to clinical complications and inflammatory control. The objective was to compare hemodynamic features and cytokine levels in the blood, lung, and bronchoalveolar lavage (BAL) fluids of animals subjected to CT or RS with or without VNS.

          Methods

          Twenty-four minipigs were subjected to 12 animals CT and 12 animals RS, with or without VNS, and accompanied 24 h later by pulmonary lobectomy. Blood samples for evaluating the hemodynamic parameters were collected before the surgical preparation, immediately after the beginning of VNS, and every 4 h until 24 h after the lobectomy. BAL fluid and lung tissue were collected at the end of the experiment. Cytokine levels were evaluated in the blood, BAL fluid, and lung tissues.

          Results

          VNS maintained a more stable heart rate during POP and decreased the incidence of overall cardiac complications while preventing increase in IL-6 levels 12 h after lobectomy, compared to sham animals. No differences were found in cytokine expression in the BAL fluid and lung tissue in any of the studied groups.

          Conclusions

          Taken together, our data suggested that VNS should be considered a non-pharmacological tool in the prevention of the exacerbated inflammatory response responsible for severe clinical complications, especially in more aggressive surgical procedures.

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          Most cited references33

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          The pro- and anti-inflammatory properties of the cytokine interleukin-6.

          Interleukin-6 is a cytokine not only involved in inflammation and infection responses but also in the regulation of metabolic, regenerative, and neural processes. In classic signaling, interleukin-6 stimulates target cells via a membrane bound interleukin-6 receptor, which upon ligand binding associates with the signaling receptor protein gp130. Gp130 dimerizes, leading to the activation of Janus kinases and subsequent phosphorylation of tyrosine residues within the cytoplasmic portion of gp130. This leads to the engagement of phosphatase Src homology domains containing tyrosin phosphatase-2 (SHP-2) and activation of the ras/raf/Mitogen-activated protein (MAP) kinase (MAPK) pathway. In addition, signal transducer and activator of transcription factors are recruited, which are phosphorylated, and consequently dimerize whereupon they translocate into the nucleus and activate target genes. Interestingly, only few cells express membrane bound interleukin-6 receptor whereas all cells display gp130 on the cell surface. While cells, which only express gp130, are not responsive to interleukin-6 alone, they can respond to a complex of interleukin-6 bound to a naturally occurring soluble form of the interleukin-6 receptor. Therefore, the generation of soluble form of the interleukin-6 receptor dramatically enlarges the spectrum of interleukin-6 target cells. This process has been named trans-signaling. Here, we review the involvement of both signaling modes in the biology of interleukin-6. It turns out that regenerative or anti-inflammatory activities of interleukin-6 are mediated by classic signaling whereas pro-inflammatory responses of interleukin-6 are rather mediated by trans-signaling. This is important since therapeutic blockade of interleukin-6 by the neutralizing anti-interleukin-6 receptor monoclonal antibody tocilizumab has recently been approved for the treatment of inflammatory diseases. This article is part of a Special Issue entitled: 11th European Symposium on Calcium. 2011 Elsevier B.V. All rights reserved.
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            The inflammatory reflex.

            Inflammation is a local, protective response to microbial invasion or injury. It must be fine-tuned and regulated precisely, because deficiencies or excesses of the inflammatory response cause morbidity and shorten lifespan. The discovery that cholinergic neurons inhibit acute inflammation has qualitatively expanded our understanding of how the nervous system modulates immune responses. The nervous system reflexively regulates the inflammatory response in real time, just as it controls heart rate and other vital functions. The opportunity now exists to apply this insight to the treatment of inflammation through selective and reversible 'hard-wired' neural systems.
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              Non–Small Cell Lung Cancer, Version 5.2017, NCCN Clinical Practice Guidelines in Oncology

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                Author and article information

                Journal
                Ann Transl Med
                Ann Transl Med
                ATM
                Annals of Translational Medicine
                AME Publishing Company
                2305-5839
                2305-5847
                06 July 2023
                30 August 2023
                : 11
                : 10
                : 347
                Affiliations
                [1 ]deptInstituto do Coração , University of Sao Paulo Medical School , Sao Paulo, Brazil;
                [2 ]Hospital Sírio-Libanês , Sao Paulo, Brazil;
                [3 ]deptLIM/23, Institute of Psychiatry , University of Sao Paulo Medical School , Sao Paulo, Brazil;
                [4 ]deptDepartment of Neurology , University of Sao Paulo Medical School , Sao Paulo, Brazil;
                [5 ]deptCenter for Neuroplasticity and Pain (CNAP), Department of Health Science and Technology, Faculty of Medicine , Aalborg University , Aalborg, Denmark
                Author notes

                Contributions: (I) Conception and design: EA Carvalho, RM Terra, AC Pinheiro Campos, RCR Martinez, RL Pagano, JM Real, DC de Andrade, PM Pêgo Fernandes; (II) Administrative support: AC Pinheiro Campos, RCR Martinez, RL Pagano, JM Real; (III) Provision of study materials or patients: EA Carvalho, RM Terra, AC Pinheiro Campos, RCR Martinez, RL Pagano, JM Real; (IV) Collection and assembly of data: EA Carvalho, RM Terra; (V) Data analysis and interpretation: EA Carvalho, RM Terra, AC Pinheiro Campos, RCR Martinez, RL Pagano, JM Real, DC de Andrade, PM Pêgo Fernandes; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.

                Correspondence to: Erlon de Avila Carvalho, Thoracic Surgeon, MD, PhD. Instituto do Coração, University of Sao Paulo Medical School, Avenue Dr. Enéas Carvalho de Aguiar, 44-Cerqueira César, São Paulo, SP, Brazil; Hospital Sírio-Libanês, Sao Paulo, Brazil. Email: erlon.avila@ 123456gmail.com .
                [^]

                ORCID: Erlon de Avila Carvalho, 0000-0002-5587-937X; Ricardo Mingarini Terra, 0000-0001-8577-8708; Ana Carolina Pinheiro Campos, 0000-0003-2901-5823; Raquel Chacon Ruiz Martinez, 0000-0002-8396-6251; Rosana Lima Pagano, 0000-0002-5351-6575; Mariane Tami Amano, 0000-0003-4321-3375; Juliana Monte Real, 0000-0003-0970-1519; Daniel Ciampi de Andrade, 0000-0003-3411-632X; Paulo Manuel Pêgo Fernandes, 0000-0001-7243-5343.

                Article
                atm-11-10-347
                10.21037/atm-22-2919
                10477644
                37675307
                d68a3b8c-7fde-4fae-828c-9a8b4eee78d1
                2023 Annals of Translational Medicine. All rights reserved.

                Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0.

                History
                : 02 June 2022
                : 08 February 2023
                Funding
                Funded by: The São Paulo Research Foundation
                Award ID: No. FAPESP-14/24526-4
                Funded by: the Hospital Sírio-Libanês
                Categories
                Original Article

                vagal stimulation,thoracic surgery,pigs,inflammation,complication

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