Cytokine Filtration Modulates Pulmonary Metabolism and Edema Formation During Ex Vivo Lung Perfusion

Cosgun, Tugba; Arni, Stephan; Trinkwitz, Michael; Fehlings, Stefan; Cesarovic, Nikola; Frauenfelder, Thomas; Weder, W.; İnci, İlhan

doi:10.1016/j.healun.2016.01.393

Cited by 8 publications

(10 citation statements)

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“…This was associated with a significant improvement in graft function. [14,15] In contrast, our findings did not show any difference in functional and inflammatory parameters between the treatment and sham group. We are uncertain whether the in-vivo setting could have masked the net effect and benefit of the filter, and this should be clarified in future studies.…”

Section: Discussioncontrasting

confidence: 92%

“…Therefore, our results are not consistent with previous publications using cytokine filters in inflammation-related diseases, including ex vivo lung perfusion. [14,15] Although we must clearly emphasize at this point that, to the best of our knowledge, we were the first to use the cytokine filter between a veno-venous bypass system in a porcine lung transplantation model. A recent review by Köhler et al examined the therapeutic modulation of CytoSorb®.…”

Section: Discussionmentioning

confidence: 99%

“…In a large animal model, Iskender et al reported that cytokine filtration with CytoSorb® during EVLP resulted in improved airway pressure and dynamic compliance, decreased electrolyte imbalance and pulmonary edema when the lungs were still mounted in the system. [14] When the lungs were treated with CytoSorb® during EVLP, and transplanted afterwards, graft function was superior compared to non-treated control lungs. [15] Currently there is no evidence whether cytokine filtration in vivo, immediately after LTx (without prior EVLP) can modify the onset and course of graft dysfunction.…”

Section: Introductionmentioning

confidence: 98%

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Can we attenuate ischaemia-reperfusion injury of allografts in a porcine left lung transplant models by adsorption of cytokines?

Frick

Orlitová

Bleeser

et al. 2022

European Journal of Cardio-Thoracic Surgery

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Background Primary graft dysfunction resulting from ischaemia-reperfusion injury (IRI) remains a major obstacle after lung transplantation (LTx) and is associated with morbidity and mortality. Continuous release of inflammatory cytokines, due to the process of ischaemia and reperfusion, triggers a complex cascade of apoptosis and necrosis resulting in graft dysfunction. Previous studies demonstrated successful graft improvement by cytokine filtration during ex vivo lung perfusion (EVLP). We hypothesize that plasma cytokine filtration with CytoSorb® during in vivo graft perfusion immediately after implantation may attenuate IRI after left LTx in a porcine model. Materials and Methods Left porcine lung transplantation was performed with allografts preserved for 24 hours at 4 °C. In the treatment group [T] (n = 7), a veno-venous shunt was created to insert the cytokine filter (CytoSorbents, Berlin, Germany). In the sham group [S] (n = 4) the shunt was created without the filter. Haemodynamic parameters, lung mechanics, blood gases and plasma cytokines were assessed during 6-hours in vivo reperfusion. Results During 6 hours of reperfusion, significant differences in plasma pro-inflammatory cytokine (IFN-α, IFN-γ, and IL-6) concentrations were observed between [T] and [S], but surprisingly with higher plasma levels in the [T] group. Plasma concentrations of other pro-inflammatory cytokines (IL-1β, IL-12p40, IL-4, IL-6, IL-8, IFN-α, IFN-γ, and TNF-α) and anti-inflammatory cytokines (IL-10) did not find any evidence for a difference. Furthermore, our study failed to show meaningful difference in haemodynamics and blood gases. Also, no statistically significant differences were found between [T] and [S] in biopsies and wet-to-dry ratio at the end of the experiment. Conclusions In our porcine left lung transplantation model cytokine filtration did not achieve the intended effect. This is in contrast to previous studies with CytoSorb® use during ex vivo lung perfusion as a surrogate LTx model. Our findings might highlight the fact that the theoretical benefit of inserting an additional cytokine adsorber to improve graft function in clinical practice should be critically evaluated with further studies.

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Section: Discussioncontrasting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

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Can we attenuate ischaemia-reperfusion injury of allografts in a porcine left lung transplant models by adsorption of cytokines?

Frick

Orlitová

Bleeser

et al. 2022

European Journal of Cardio-Thoracic Surgery

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“…Haemoadsorption with an incorporated cytokine filter has been used to reduce the inflammatory response during kidney machine perfusion resulting in improved renal blood flow, albeit without significantly influencing renal function [ 34 ]. With regard to lung machine perfusion, filter-based cytokine removal has been shown to decrease the development of pulmonary edema with uncertain effects on clinical pulmonary function post engraftment [ 35 ].…”

Section: Discussionmentioning

confidence: 99%

Interleukin-18 and High-Mobility-Group-Protein B1 are Early and Sensitive Indicators for Cell Damage During Normothermic Machine Perfusion after Prolonged Cold Ischemic Storage of Porcine Liver Grafts

Beetz¹,

Cammann²,

Weigle³

et al. 2022

Transpl Int

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In the era of organ machine perfusion, experimental models to optimize reconditioning of (marginal) liver grafts are needed. Although the relevance of cytokine signatures in liver transplantation has been analyzed previously, the significance of molecular monitoring during normothermic machine perfusion (NMP) remains elusive. Therefore, we developed a porcine model of cold ischemic liver graft injury after prolonged static cold storage (SCS) and subsequent NMP: Livers obtained from ten minipigs underwent NMP for 6 h directly after procurement (control group) or after 20 h of SCS. Grafts after prolonged SCS showed significantly elevated AST, ALT, GLDH and GGT perfusate concentrations, and reduced lactate clearance. Bile analyses revealed reduced bile production, reduced bicarbonate and elevated glucose concentrations after prolonged SCS. Cytokine analyses of graft perfusate simultaneously demonstrated an increase of pro-inflammatory cytokines such as Interleukin-1α, Interleukin-2, and particularly Interleukin-18. The latter was the only significantly elevated cytokine compared to controls, peaking as early as 2 h after reperfusion (11,012 ng/ml vs. 1,493 ng/ml; p = 0.029). Also, concentrations of High-Mobility-Group-Protein B1 were significantly elevated after 2 h of reperfusion (706.00 ng/ml vs. 148.20 ng/ml; p < 0.001) and showed positive correlations with AST (r2 = 0.846) and GLDH (r2 = 0.918) levels. Molecular analyses during reconditioning of liver grafts provide insights into the degree of inflammation and cell damage and could thereby facilitate future interventions during NMP reducing acute and chronic graft injury.

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“…and development of pulmonary edema. 41 data showed elevations in inflammatory cytokines in EVLP2, which may be partially associated with impaired organ function. Therefore, our data might represent the disadvantage of intermittent EVLP.…”

Section: Discussionmentioning

confidence: 84%

Intermittent Ex Vivo Lung Perfusion in a Porcine Model for Prolonged Lung Preservation

Sakanoue,

Okamoto,

Ayyat

et al. 2023

Transplantation

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Background. Ex vivo lung perfusion expands the lung transplant donor pool and extends preservation time beyond cold static preservation. We hypothesized that repeated regular ex vivo lung perfusion would better maintain lung grafts. Methods. Ten pig lungs were randomized into 2 groups. The control underwent 16 h of cold ischemic time and 2 h of cellular ex vivo lung perfusion. The intermittent ex vivo lung perfusion group underwent cold ischemic time for 4 h, ex vivo lung perfusion (first) for 2 h, cold ischemic time for 10 h, and 2 h of ex vivo lung perfusion (second). Lungs were assessed, and transplant suitability was determined after 2 h of ex vivo lung perfusion. Results. The second ex vivo lung perfusion was significantly associated with better oxygenation, limited extravascular water, higher adenosine triphosphate, reduced intraalveolar edema, and well-preserved mitochondria compared with the control, despite proinflammatory cytokine elevation. No significant difference was observed in the first and second perfusion regarding oxygenation and adenosine triphosphate, whereas the second was associated with lower dynamic compliance and higher extravascular lung water than the first. Transplant suitability was 100% for the first and 60% for the second ex vivo lung perfusion, and 0% for the control. Conclusions. The second ex vivo lung perfusion had a slight deterioration in graft function compared to the first. Intermittent ex vivo lung perfusion created a better condition for lung grafts than cold static preservation, despite cytokine elevation. These results suggested that intermittent ex vivo lung perfusion may help prolong lung preservation.

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Cytokine Filtration Modulates Pulmonary Metabolism and Edema Formation During Ex Vivo Lung Perfusion

Cited by 8 publications

References 0 publications

Can we attenuate ischaemia-reperfusion injury of allografts in a porcine left lung transplant models by adsorption of cytokines?

Can we attenuate ischaemia-reperfusion injury of allografts in a porcine left lung transplant models by adsorption of cytokines?

Interleukin-18 and High-Mobility-Group-Protein B1 are Early and Sensitive Indicators for Cell Damage During Normothermic Machine Perfusion after Prolonged Cold Ischemic Storage of Porcine Liver Grafts

Intermittent Ex Vivo Lung Perfusion in a Porcine Model for Prolonged Lung Preservation

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