Random allogeneic blood transfusion in pigs: characterisation of a novel experimental model

Ziebart, Alexander; Schaefer, Moritz M; Thomas, Rainer; Kamuf, Jens; García-Bardon, Andreas; Möllmann, Christian; Ruemmler, Robert; Heid, F.; Schad, Arno; Hartmann, Erik K.

doi:10.7717/peerj.7439

Cited by 3 publications

(9 citation statements)

References 37 publications

(55 reference statements)

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“…The main causes behind this are the transfusion of incompatible blood, allergenic reaction, transfusion-related acute lung injury (TRALI) or transfusion-associated circulatory overload (TACO). Compared with human blood, porcine blood offers several advantages ( Ziebart et al, 2019 ; Smith et al, 2006 ). Ziebart et al (2019) demonstrated that random allogenic blood transfusion in pigs was not associated with adverse effects of incompatibility, upregulation of systemic and local (brain/lung) inflammatory markers and did not affect lung function.…”

Section: Discussionmentioning

confidence: 99%

“…The anaesthesia and instrumentation are highly standardized in our group and were previously reported ( Ziebart et al, 2019 ; Kamuf et al, 2018 ). To minimise stress, the animals ( Sus scrofa domestica) stayed in their familiar environment for as long as possible.…”

Section: Methodsmentioning

confidence: 99%

“…At the end of the protocol, the lung and brain were each removed en-bloc. Cortex and hippocampus samples were cryopreserved for an mRNA expression analysis of inflammatory mediators like interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), inducible nitric oxide synthase (iNOS) and soluble lipocalin-2 (sLCN-2) by real-time polymerase chain reaction (rt-PCR; Lightcycler 480 PCR System; Roche Applied Science, Penzberg, Germany), as described in detail by Ziebart et al (2019) mRNA expression was used to better compare the results with previous studies and normalised to peptidylprolyl isomerase A (PPIA) ( Ziebart et al, 2019 ). To determine the lung damage, we used a standardised scoring system, as described in detail from our group previously ( Ziebart et al, 2014 ).…”

Section: Methodsmentioning

confidence: 99%

“…Group size was adjusted comparably with recently published studies ( Ziebart et al, 2019 ; Hartmann et al, 2014 ). The values are displayed as the mean and standard deviation (SD) or violin plots (median and interquartile range).…”

Section: Methodsmentioning

confidence: 99%

“…Patients who have survived ARDS often develop some degree of cognitive deterioration, which has long-term effects on the brain because of the intensive therapy required ( Hopkins & Jackson, 2006 ). A common theory is that there is a systemic distribution of inflammatory mediators released from the affected organ and transmitted via the bloodstream to other organs, such as the brain ( Mrozek, Constantin & Geeraerts, 2015 ; Ziebart et al, 2019 ; Klein et al, 2016 ; Hegeman et al, 2009 ). Three transmission pathways of lung–brain cross-talk have been described: a humoural, a cellular and a neuronal pathway ( López-Aguilar et al, 2013 ).…”

Section: Introductionmentioning

confidence: 99%

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Lung–brain ‘cross-talk’: systemic propagation of cytokines in the ARDS via the bloodstream using a blood transfusion model does not influence cerebral inflammatory response in pigs

Rissel¹,

Schaefer²,

Kamuf³

et al. 2022

PeerJ

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Background Interorgan cross-talk describes the phenomenon in which a primarily injured organ causes secondary damage to a distant organ. This cross-talk is well known between the lung and brain. One theory suggests that the release and systemic distribution of cytokines via the bloodstream from the primarily affected organ sets in motion proinflammatory cascades in distant organs. In this study, we analysed the role of the systemic distribution of cytokines via the bloodstream in a porcine ARDS model for organ cross-talk and possible inflammatory changes in the brain. Methods After approval of the State and Institutional Animal Care Committee, acute respiratory distress syndrome (ARDS) induction with oleic acid injection was performed in seven animals. Eight hours after ARDS induction, blood (35–40 ml kg–1) was taken from these seven ‘ARDS donor’ pigs. The collected ‘ARDS donor’ blood was transfused into seven healthy ‘ARDS-recipient’ pigs. Three animals served as a control group, and blood from these animals was transfused into three healthy pigs after an appropriate ventilation period. All animals were monitored for 8 h using advanced cardiorespiratory monitoring. Postmortem assessment included cerebral (hippocampal and cortex) mediators of early inflammatory response (IL-6, TNF-alpha, iNOS, sLCN-2), wet-to-dry ratio and lung histology. TNF-alpha serum concentration was measured in all groups. Results ARDS was successfully induced in the ‘ARDS donor’ group, and serum TNF-alpha levels were elevated compared with the ‘ARDS-recipient’ group. In the ‘ARDS-recipient’ group, neither significant ARDS alterations nor upregulation of inflammatory mediators in the brain tissue were detected after high-volume random allogenic ‘ARDS-blood’ transfusion. The role of the systemic distribution of inflammatory cytokines from one affected organ to another could not be confirmed in this study.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Lung–brain ‘cross-talk’: systemic propagation of cytokines in the ARDS via the bloodstream using a blood transfusion model does not influence cerebral inflammatory response in pigs

Rissel¹,

Schaefer²,

Kamuf³

et al. 2022

PeerJ

Self Cite

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Metabolic and textural changes in the brain of non‐small cell lung cancer patients: A total‐body positron emission tomography/computed tomography study

Xie,

Lu,

et al. 2023

iRADIOLOGY

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Background: Brain metastases are frequent complications for lung cancer patients. However, changes in the brain of lung cancer patients have received little attention. We aimed to explore whether alterations in brain glucose uptake and brain texture occur in non-small cell lung cancer (NSCLC) patients and to investigate associations between brain alterations and NSCLC via the uEXPLORER positron emission tomography/computed tomography (PET/CT) system. Methods:In total, 105 participants were enrolled, including 55 healthy controls and 50 NSCLC patients. Images were acquired using the PET/CT system. Standardized uptake values normalized by lean body mass were calculated as indicators of glucose uptake. Correlation analysis was conducted between aberrant brain glucose uptake, glucose uptake of cancer lesions, and concentrations of serum lung cancer markers. Radiomics was used to investigate whether features extracted from regions with altered brain glucose uptake could serve as biomarkers of lung cancer progression.Results: Compared with healthy controls, NSCLC patients showed decreased standardized uptake values normalized by lean body mass in the left insula, medial frontal gyrus, and anterior cingulate. Correlation analysis demonstrated that glucose uptake of the anterior cingulate was negatively correlated with serum lung cancer marker concentrations. Radiomic features on PET/CT images of the above brain regions could classify NSCLC patients and healthy controls with an accuracy of 79%.

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Effect of fluid resuscitation on cerebral integrity

Ziebart

Breit

Ruemmler

et al. 2021

European Journal of Anaesthesiology

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BACKGROUND The treatment of haemorrhagic shock is a challenging task. Colloids have been regarded as standard treatment, but their safety and benefit have been the subject of controversial debates. Negative effects, including renal failure and increased mortality, have resulted in restrictions on their administration. The cerebral effects of different infusion regimens are largely unknown. OBJECTIVES The current study investigated the impact of gelatine-polysuccinate, hydroxyethyl starch (HES) and balanced electrolyte solution (BES) on cerebral integrity, focusing on cerebral inflammation, apoptosis and blood flow in pigs. DESIGN Randomised experimental study. SETTING University-affiliated large animal research unit. ANIMALS Twenty-four juvenile pigs aged 8 to 12 weeks. INTERVENTION Haemorrhagic shock was induced by controlled arterial blood withdrawal to achieve a combination of relevant blood loss (30 to 40 ml kg−1) and haemodynamic deterioration. After 30 min of shock, fluid resuscitation was started with either gelatine-polysuccinate, HES or BES. The animals were then monitored for 4 h. MAIN OUTCOME MEASURES Cerebral perfusion and diffusion were measured via arterial-spin-labelling MRI. Peripheral tissue perfusion was evaluated via white light spectroscopy. Cortical and hippocampal samples were collected at the end of the experiment. The numbers of cerebral cell nuclei were counted and mRNA expression of markers for cerebral apoptosis [glucose transporter protein type 1 (SLC2A), lipocalin 2 (LCN-2), aquaporin-4 (AQP4)] and inflammation [IL-6, TNF-α, glial fibrillary acidic protein (GFAP)] were determined. RESULTS The three fluid protocols all stabilised the macrocirculation. Fluid resuscitation significantly increased the cerebral perfusion. Gelatine-polysuccinate and HES initially led to a higher cardiac output but caused haemodilution. Cerebral cell counts (as cells μm−2) were lower after colloid administration in the cortex (gelatine-polysuccinate, 1.8 ± 0.3; HES, 1.9 ± 0.4; each P < 0.05 vs. BES, 2.3 ± 0.2) and the hippocampus (gelatine-polysuccinate, 0.8 ± 0.2; HES, 0.9 ± 0.2; each P < 0.05 vs. BES, 1.1 ± 0.1). After gelatine-polysuccinate, the hippocampal SLC2A and GFAP were lower. After gelatine-polysuccinate, the cortical LCN-2 and TNF-α expression levels were increased (each P < 0.05 vs. BES). CONCLUSION In a porcine model, fluid resuscitation by colloids, particularly gelatine-polysuccinate, was associated with the occurrence of cerebral injury. ETHICAL APPROVAL NUMBER 23 177-07/G 15-1-092; 01/2016.

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Random allogeneic blood transfusion in pigs: characterisation of a novel experimental model

Cited by 3 publications

References 37 publications

Lung–brain ‘cross-talk’: systemic propagation of cytokines in the ARDS via the bloodstream using a blood transfusion model does not influence cerebral inflammatory response in pigs

Lung–brain ‘cross-talk’: systemic propagation of cytokines in the ARDS via the bloodstream using a blood transfusion model does not influence cerebral inflammatory response in pigs

Metabolic and textural changes in the brain of non‐small cell lung cancer patients: A total‐body positron emission tomography/computed tomography study

Effect of fluid resuscitation on cerebral integrity

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