Potential Impact of Local Anesthetics Inducing Granulocyte Arrest and Altering Immune Functions on Perioperative Outcome

Kolle, Gesche; Metterlein, Thomas; Gruber, Michael; Seyfried, Timo; Petermichl, Walter; Pfaehler, Sophie-Marie; Bitzinger, Diane; Wittmann, Sigrid; Bredthauer, Andre

doi:10.2147/jir.s275525

Cited by 11 publications

(21 citation statements)

References 50 publications

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“…Propofol appears to decrease NET formation by activated neutrophils through the inhibition of hypochlorus acid production and MAPK/ERK [ 153 ]. Local anaesthetics in clinically used doses, decreased, in a dose-dependent manner, the time to onset of maximal ROS production and half-maximal NETosis [ 154 ].…”

Section: Biomarkers Anaesthetic Technique and Cancermentioning

confidence: 99%

Breast Cancer and Anaesthesia: Genetic Influence

Ponferrada

Orriach

Ruiz

et al. 2021

IJMS

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Breast cancer is the leading cause of mortality in women. It is a heterogeneous disease with a high degree of inter-subject variability even in patients with the same type of tumor, with individualized medicine having acquired significant relevance in this field. The clinical and morphological heterogeneity of the different types of breast tumors has led to a diversity of staging and classification systems. Thus, these tumors show wide variability in genetic expression and prognostic biomarkers. Surgical treatment is essential in the management of these patients. However, the perioperative period has been found to significantly influence survival and cancer recurrence. There is growing interest in the pro-tumoral effect of different anaesthetic and analgesic agents used intraoperatively and their relationship with metastatic progression. There is cumulative evidence of the influence of anaesthetic techniques on the physiopathological mechanisms of survival and growth of the residual neoplastic cells released during surgery. Prospective randomized clinical trials are needed to obtain quality evidence on the relationship between cancer and anaesthesia. This document summarizes the evidence currently available about the effects of the anaesthetic agents and techniques used in primary cancer surgery and long-term oncologic outcomes, and the biomolecular mechanisms involved in their interaction.

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Section: Biomarkers Anaesthetic Technique and Cancermentioning

confidence: 99%

Breast Cancer and Anaesthesia: Genetic Influence

Ponferrada

Orriach

Ruiz

et al. 2021

IJMS

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“…For flow cytometry, granulocyte activation was also initiated with fMLP with PMA serving as positive control. [21][22][23][24] Propofol is a widely used drug for the induction and maintenance of anesthesia and sedation and is also considered a first-line agent for patients suffering from COVID-19. 27,28 It is often used as a monotherapy for sedation, and clinically achieved plasma levels range from 2 to 30 µg/mL.…”

Section: Discussionmentioning

confidence: 99%

“…The experimental setup was based on previous studies of ours. [20][21][22][23][24] In brief, whole blood was drawn from 34 healthy blood donors (Table 1) with their informed consent and as approved by the University of Regensburg's ethics committee (File number 18-1210-10) and was conducted in accordance with the Declaration of Helsinki. This blood was then anticoagulated using lithium heparin.…”

Section: Granulocyte Preparationmentioning

confidence: 99%

Propofol Ameliorates Exaggerated Human Neutrophil Activation in a LPS Sepsis Model

Bredthauer¹,

Geiger²,

Gruber³

et al. 2021

JIR

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Background Sepsis is a leading cause of morbidity and mortality worldwide. Many patients suffering from sepsis are treated on intensive care units and many of them require mechanical ventilation under sedation or general anesthesia. Propofol, a drug used for these purposes, is known to interact with polymorphonuclear granulocytes (PMNs). Therefore, the aim of this study was to investigate the influence of propofol on PMN functions after experimental Gram-negative induced sepsis using lipopolysaccharide (LPS) stimulation. Methods A total of 34 granulocyte-enriched samples were collected from healthy subjects. PMNs were isolated by density gradient centrifugation and incubated simultaneously with either 6 µg/mL or 60 µg/mL propofol, or none (control). Additionally, the experimental sepsis samples were incubated with either 40 pg/mL or 400 pg/mL LPS. Live cell imaging was conducted in order to observe granulocyte chemotactic migration, ROS production, and NETosis. Flow cytometry was used to analyze viability and antigen expression. Results Propofol led to significantly reduced PMN track length (p < 0.001) and track speed (p < 0.014) after LPS-induced sepsis in a dose-dependent manner. NETosis (p = 0.018) and ROS production (p = 0.039) were accelerated by propofol without LPS incubation, indicating improved immune function. Propofol also ameliorated LPS-induced increased NETosis and ROS-production. Antigen expression for CD11b, CD62l and CD66b was unaffected by propofol. Conclusion Propofol improves LPS-induced exaggerated PMN activation in an ex vivo model. Beneficial effects due to restored immune function in septic patients might be possible, but needs further investigation.

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“…The experimental setup was based on previous experiments published in [ 22 , 25 , 26 ]. To observe PMN behavior, a chemotactic assay was performed using 3D-µ-slides (ibidi© GmbH, Martinsried, Germany) according to the manufacturer’s instructions.…”

Section: Methodsmentioning

confidence: 99%

“…The fact that PMNs are essential for appropriate tissue repair becomes apparent in neutropenic patients, who often have wound healing deficits [ 20 ]. Furthermore, PMN functions may be modified with several drugs, leading to clinically relevant immunomodulation [ 21 , 22 , 23 ]. In these studies, the typical time course of PMN reactions is described as follows.…”

Section: Introductionmentioning

confidence: 99%

Cold Atmospheric Plasma Promotes the Immunoreactivity of Granulocytes In Vitro

et al. 2021

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Cold atmospheric plasma (CAP) reduces bacteria and interacts with tissues and cells, thus improving wound healing. The CAP-related induction of neutrophils was recently described in stained sections of wound tissue in mice. Consequently, this study aimed to examine the functionality of human polymorphonuclear cells (PMN)/granulocytes through either a plasma-treated solution (PTS) or the direct CAP treatment with different plasma modes and treatment durations. PTS analysis yielded mode-dependent differences in the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS) after CAP treatment. Live-cell imaging did not show any chemo-attractive or NETosis-inducing effect on PMNs treated with PTS. The time to maximum ROS production (TmaxROS) in PMNs was reduced by PTS and direct CAP treatment. PMNs directly treated with CAP showed an altered cell migration dependent on the treatment duration as well as decreased TmaxROS without inducing apoptosis. Additionally, flow cytometry showed enhanced integrin and selectin expression, as a marker of activation, on PMN surfaces. In conclusion, the modification of PMN immunoreactivity may be a main supporting mechanism for CAP-induced improvement in wound healing.

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Potential Impact of Local Anesthetics Inducing Granulocyte Arrest and Altering Immune Functions on Perioperative Outcome

Cited by 11 publications

References 50 publications

Breast Cancer and Anaesthesia: Genetic Influence

Breast Cancer and Anaesthesia: Genetic Influence

Propofol Ameliorates Exaggerated Human Neutrophil Activation in a LPS Sepsis Model

Cold Atmospheric Plasma Promotes the Immunoreactivity of Granulocytes In Vitro

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