Contributing factors in the development of acute lung injury in a murine double hit model

Störmann, Philipp; Becker, Nils; Künnemeyer, Leander; Wutzler, Sebastian; Vollrath, Jan Tilmann; Lustenberger, Thomas; Hildebrand, Frank; Marzi, Ingo; Relja, Borna

doi:10.1007/s00068-019-01121-5

Cited by 11 publications

(27 citation statements)

References 52 publications

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“…Thus, in line with the two-hit hypothesis, a traumatic insult as the first hit, followed by secondary surgeries or complications, may lead to detrimental outcomes. Consistent with the findings of other researchers, it was found that isolated experimental lung trauma induced a profound inflammatory reaction; however, it was insufficient to establish the ongoing pathological pulmonary changes associated with ALI ( 7 , 8 ). However, secondary CLP following TxT, as applied herein, reflected the human etiology of indirect lung damage ending in ALI ( 7 , 9 - 11 ).…”

Section: Introductionsupporting

confidence: 80%

“…Consistent with the findings of other researchers, it was found that isolated experimental lung trauma induced a profound inflammatory reaction; however, it was insufficient to establish the ongoing pathological pulmonary changes associated with ALI ( 7 , 8 ). However, secondary CLP following TxT, as applied herein, reflected the human etiology of indirect lung damage ending in ALI ( 7 , 9 - 11 ). Another murine 'double-hit' model that includes CLP, followed by inducing pneumonia via Pseudomonas aeruginosa 4-7 days later, significantly improved survival when pneumonia was induced after 7 days.…”

Section: Introductionsupporting

confidence: 80%

“…Furthermore, the recruitment of neutrophils to injured lung tissue, which is primarily responsible for pulmonary dysfunction following lung contusion, has been shown to be dependent on the expression of CXCL1, among other pro-inflammatory factors ( 6 ). Recently, the authors demonstrated that a 'double-hit' model of TxT, followed by cecal ligation and puncture (CLP) as the second hit, which was also applied in the underlying study, increased the expression of pro-inflammatory chemokines and cytokines, including CXCL1 ( 7 ). Thus, in line with the two-hit hypothesis, a traumatic insult as the first hit, followed by secondary surgeries or complications, may lead to detrimental outcomes.…”

Section: Introductionmentioning

confidence: 99%

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Early local neutralization of CC16 in sepsis‑induced ALI following blunt chest trauma leads to delayed mortality without benefitting overall survival

et al. 2020

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Blunt thoracic trauma (TxT) is a common injury pattern in polytraumatized patients. When combined with a secondary trigger, TxT often results in acute lung injury (ALI), which negatively affects outcomes. Recent findings suggest that ALI is caused by both local and systemic inflammatory reactions. Club cell protein (CC)16 is an anti-inflammatory peptide associated with lung injury following TxT. Recently, the anti-inflammatory properties of endogenous CC16 in a murine model of TxT with subsequent cecal-ligation and puncture (CLP) as the secondary hit were demonstrated by our group. The present study aimed to determine whether CC16 neutralization improves survival following 'double-hit'-induced ALI. For this purpose, a total of 120 C57BL/6N mice were subjected to TxT, followed by CLP after 24 h. Sham-operated animals underwent anesthesia without the induction of TxT + CLP. CC16 neutralization was performed by providing a CC16 antibody intratracheally following TxT (early) or following CLP (late). Survival was assessed in 48 animals for 6 days after CLP. Sacrifice was performed 6 or 24 h post-CLP to evaluate the anti-inflammatory effect of CC16. The results revealed that CC16 neutralization enhanced pro-inflammatory CXCL1 levels, thereby confirming the anti-inflammatory characteristics of CC16 in this model. Early CC16 neutralization immediately following TxT significantly prolonged survival within 60 h; however, the survival rate did not change until 6 days post-trauma. Late CC16 neutralization did not provide any survival benefits. On the whole, the present study demonstrated that neutralizing CC16 confirmed its anti-inflammatory potential in this double-hit ALI model. Early CC16 neutralization prolonged survival within 60 h; however, no survival benefits were observed after 6 days post-CLP in any group.

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Section: Introductionsupporting

confidence: 80%

Section: Introductionsupporting

confidence: 80%

Section: Introductionmentioning

confidence: 99%

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Early local neutralization of CC16 in sepsis‑induced ALI following blunt chest trauma leads to delayed mortality without benefitting overall survival

et al. 2020

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“…Both in vitro and in vivo modeling of the complex injury patterns of polytrauma and the subsequent immune response remain difficult. Although valid and reliable murine and porcine animal models have been developed within the NTF group [28][29][30], the translational process to the heterogenous situation in the clinical setting of polytrauma remains crucial. Noteworthy, despite improved treatment strategies with regard to traumatic injuries as well as to the posttraumatic immune response, both mortality and disability rates remain alarmingly high.…”

Section: Current Stagementioning

confidence: 99%

A nationwide fluidics biobank of polytraumatized patients: implemented by the Network “Trauma Research” (NTF) as an expansion to the TraumaRegister DGU® of the German Trauma Society (DGU)

Relja

Huber‐Lang

Griensven

et al. 2019

Eur J Trauma Emerg Surg

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To decrypt the complexity of the posttraumatic immune responses and to potentially identify novel research pathways for exploration, large-scale multi-center projects including not only in vivo and in vitro modeling, but also temporal sample and material collection along with clinical data capture from multiply injured patients is of utmost importance. To meet this gap, a nationwide biobank for fluidic samples from polytraumatized patients was initiated in 2013 by the task force Network "Trauma Research" (Netzwerk Traumaforschung, NTF) of the German Trauma Society (Deutsche Gesellschaft für Unfallchirurgie e.V., DGU). The NTF-Biobank completes the clinical NTF-Biobank Database and complements the TR-DGU with temporal biological samples from multiply injured patients. The concept behind the idea of the NTF-Biobank was to create a robust interface for meaningful innovative basic, translational and clinical research. For the first time, an integrated platform to prospectively evaluate and monitor candidate biomarkers and/or potential therapeutic targets in biological specimens of quality-controlled and documented patients is introduced, allowing reduction in variability of measurements with high impact due to its large sample size. Thus, the project was introduced to systemically evaluate and monitor multiply injured patients for their (patho-)physiological sequalae together with their clinical treatment strategies applied for overall outcome improval.

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“…Both studies, therefore, concluded that innovative prevention and treatment protocols for pneumonia have to be developed in future studies.Due to a significant heterogeneity of the trauma population, experimental studies are of upmost importance to investigate the underlying pathomechanisms of posttraumatic complications and to establish new strategies. A model was introduced by Stormann et al, who investigated contributing factors for the development of acute lung injury (ALI) in a murine double hit model [3]. To induce ALI, the authors induced either a double hit with blunt chest trauma and cecal ligation and puncture (CLP) or chest trauma alone.…”

mentioning

confidence: 99%

Focus on chest trauma: implications from clinical and experimental studies

Horst

Hildebrand

2020

Eur J Trauma Emerg Surg

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Chest trauma still represents one of the most frequent and devastating injuries after polytrauma. Besides the direct effects of the traumatic impact itself, lung integrity and function are also indirectly endangered by the systemic release of inflammatory mediators due to additional injuries of other body regions. Significant efforts have to be made to better understand the underlying pathomechanisms to improve diagnostic and therapeutic strategies. This issue of the European Journal of Trauma and Emergency Surgery therefore focuses on recent aspects of chest trauma based on data from clinical and experimental studies, which underlines the relevance of bidirectional translational research.The relevance of complications after chest trauma was a focus of the clinical studies of this issue. In a retrospective analysis, Huang et al. observed over an 8-year period [1] that almost 50% of the 10,362 trauma patients included in the study presented with chest trauma. Overall, thoracic injuries represented a risk factor for the development of adult respiratory distress syndrome (ARDS). However, ARDS-associated mortality was tenfold higher in patients without chest trauma. In these patients, ventilator-associated pneumonia (VAP) was the only preventable and treatable risk factor. In another clinical study, Hofman et al. analyzed the relevance of chest trauma and traumatic brain injury (TBI) in severely injured patients (ISS ≥ 16) [2]. In their retrospective analysis, chest trauma was an independent predictor of pneumonia. Pneumonia in turn represented the strongest independent predictor of in-hospital mortality, followed by combined chest trauma and TBI, TBI alone, and the duration of ventilation. The authors concluded that chest trauma seems to represent a direct risk factor, whereas TBI acts more as an indirect risk factor via a prolonged duration of ventilation. Duration of ventilation is by itself an independent predictor of pneumonia after trauma. Both studies, therefore, concluded that innovative prevention and treatment protocols for pneumonia have to be developed in future studies.Due to a significant heterogeneity of the trauma population, experimental studies are of upmost importance to investigate the underlying pathomechanisms of posttraumatic complications and to establish new strategies. A model was introduced by Stormann et al., who investigated contributing factors for the development of acute lung injury (ALI) in a murine double hit model [3]. To induce ALI, the authors induced either a double hit with blunt chest trauma and cecal ligation and puncture (CLP) or chest trauma alone. It was observed that lung injury alone was associated with moderate inflammatory changes and quick recovery while the double hit resulted in a significant activation of the inflammatory response and unfavorable outcomes. This model will help to discriminate the influence of direct (chest trauma) and indirect (e.g. systemic inflammatory response) in future experimental studies. The importance of factors potentially associated with ...

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Contributing factors in the development of acute lung injury in a murine double hit model

Cited by 11 publications

References 52 publications

Early local neutralization of CC16 in sepsis‑induced ALI following blunt chest trauma leads to delayed mortality without benefitting overall survival

Early local neutralization of CC16 in sepsis‑induced ALI following blunt chest trauma leads to delayed mortality without benefitting overall survival

A nationwide fluidics biobank of polytraumatized patients: implemented by the Network “Trauma Research” (NTF) as an expansion to the TraumaRegister DGU® of the German Trauma Society (DGU)

Focus on chest trauma: implications from clinical and experimental studies

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