Search

Abstract Air traveler numbers are predicted to reach 4.0 billion in 2024. Between 1/15,000–50,000 passengers will experience acute medical problems inflight with cardiac arrests requiring cardiopulmonary resuscitation (CPR) accounting for 0.3% of medical emergencies. Hypoxia in airplane cabins could impair oxygenation and physical performance of caregivers. We conducted a randomized controlled, double-blind study to test the hypothesis that hypoxia decreases the effectiveness in performing CPR. We randomized 24 healthcare professionals to two different study arms, each consisting of two conditions: arm (1) ‘hypoxia (FiO2 15%, equivalent to 2400 m altitude)’ versus ‘normoxia’; arm (2) ‘hypoxia + supplemental oxygen’ versus ‘normoxia + supplemental oxygen’. The order of conditions was counterbalanced and a minimum wash-out period of 24 h was granted between conditions. In each condition participants performed a 5-min cardiac compression only CPR (CCO-CPR) using a full-body manikin after one, three and six hours in an altitude chamber. Mixed ANOVAs with post-hoc false-discovery-rate adjusted pairwise comparisons indicated that although compression frequency was maintained, the number of compressions with correct depth was decreased at all times during hypoxia compared to normoxia (all p

Abstract Background Pre-hospital endotracheal intubation (ETI) is a sophisticated procedure with a comparatively high failure rate. Especially, ETI in confined spaces may result in higher difficulty, longer times, and a higher failure rate. This study analyses if Helicopter Emergency Medical Services (HEMS) intubation (time-to) success are influenced by noise, light, and restricted space in comparison to ground intubation. Available literature reporting these parameters was very limited, thus the reported differences between ETI in helicopter vs. ground by confronting parameters such as time to secure airway, first pass success rate and Cormack-Lehane Score were analysed. Methods A systematic review and meta-analysis were conducted using PUBMED, EMBASE, Cochrane Library, and Ovid on October 15th, 2022. The database search provided 2322 studies and 6 studies met inclusion and quality criteria. The research was registered with the International Prospective Register of Systematic Reviews (CRD42022361793). Results A total of six studies were selected and analysed as part of the systematic review and meta-analysis. The first pass success rate of ETI was more likely to fail in the helicopter setting as compared to the ground (82,4% vs. 87,3%), but the final success rate was similar between the two settings (96,8% vs. 97,8%). The success rate of intubation in literature was reported higher in physician-staffed HEMS than in paramedic-staffed HEMS. The impact of aircraft type and location inside the vehicle on intubation success rates was inconclusive across studies. The meta-analysis revealed inconsistent results for the mean duration of intubation, with one study reporting shorter intubation times in helicopters (13,0s vs.15,5s), another reporting no significant differences (16,5s vs. 16,8s), and a third reporting longer intubation times in helicopters (16,1s vs. 15,0s). Conclusion Further research is needed to assess the impact of environmental factors on the quality of ETI on HEMS. While the success rate of endotracheal intubation in helicopters vs. on the ground is not significantly different, the duration and time to secure the airway, and Cormack-Lehane Score may be influenced by environmental factors. However, the limited number of studies reporting on these factors highlights the need for further research in this area.

Abstract Background Despite the development of various analgesic concepts, prehospital oligoanalgesia remains very common. The present work examines prehospital analgesia by paramedics using morphine vs. nalbuphine + paracetamol. Methods Patients with out-of-hospital-analgesia performed by paramedics from the emergency medical services of the districts of Fulda (morphine) and Gütersloh (nalbuphine + paracetamol) were evaluated with regards to pain intensity at the beginning and the end of prehospital treatment using the Numeric-Rating-Scale for pain (NRS), sex, age, and complications. The primary endpoint was achievement of adequate analgesia, defined as NRS

Background: Cardiopulmonary resuscitation (CPR) is essential for saving lives during cardiac arrest, but performing CPR in extreme environments poses unique challenges. In scenarios ranging from hypogravity or microgravity to confined spaces like aeroplanes and underwater scenarios, traditional CPR techniques may be inadequate. This scoping review aims to identify alternative chest compression techniques, synthesise current knowledge, and pinpoint research gaps in resuscitation for cardiac arrest in extreme conditions. Methods: PubMed and the Cochrane Register of Controlled Trials as well as the website of ResearchGate was searched to identify relevant literature. Studies were eligible for inclusion if they evaluated alternative chest compression techniques, including manual or mixed CPR approaches, whilst assessing feasibility and effectiveness based on compression depth, rate, and/or impact on rescuer effort. Results: The database search yielded 9499 references. After screening 26 studies covering 6 different extreme environments were included (hypogravity: 2; microgravity: 9, helicopter: 1, aeroplane: 1, confined space: 11; avalanche: 2). 13 alternative chest compression techniques were identified, all of which tested using manikins to simulate cardiac arrest scenarios. Conclusion: To address the unique challenges in extreme environments, novel CPR techniques are emerging. However, evidence supporting their effectiveness remains limited.

Abstract Background Cardiopulmonary resuscitation (CPR) during hyperbaric oxygen therapy (HBOT) presents unique challenges due to limited access to patients in cardiac arrest (CA) and the distinct physiological conditions present during hyperbaric therapy. Despite these challenges, guidelines specifically addressing CPR during HBOT are lacking. This review aims to consolidate the available evidence and offer recommendations for clinical practice in this context. Materials and methods A comprehensive literature search was conducted in PubMed, EMBASE, Cochrane Library, and CINAHL using the search string: “(pressure chamber OR decompression OR hyperbaric) AND (cardiac arrest OR cardiopulmonary resuscitation OR advanced life support OR ALS OR life support OR chest compression OR ventricular fibrillation OR heart arrest OR heart massage OR resuscitation)”. Additionally, relevant publications and book chapters not identified through this search were included. Results The search yielded 10,223 publications, with 41 deemed relevant to the topic. Among these, 18 articles (primarily case reports) described CPR or defibrillation in 22 patients undergoing HBOT. The remaining 23 articles provided information or recommendations pertaining to CPR during HBOT. Given the unique physiological factors during HBOT, the limitations of current resuscitation guidelines are discussed. Conclusions CPR in the context of HBOT is a rare, yet critical event requiring special considerations. Existing guidelines should be adapted to address these unique circumstances and integrated into regular training for HBOT practitioners. This review serves as a valuable contribution to the literature on “CPR under special circumstances”.

Abstract Long duration spaceflights to the Moon or Mars are at risk for emergency medical events. Managing a hypoxemic distress and performing an advanced airway procedure such as oro-tracheal intubation may be complicated under weightlessness due to ergonomic constraints. An emergency free-floating intubation would be dangerous because of high failure rates due to stabilization issues that prohibits its implementation in a space environment. Nevertheless, we hypothesized that two configurations could lead to a high first-pass success score for intubation performed by a free-floating operator. In a non-randomized, controlled, cross-over simulation study during a parabolic flight campaign, we evaluated and compared the intubation performance of free-floating trained operators, using either a conventional direct laryngoscope in an ice-pick position or an indirect laryngoscopy with a video-laryngoscope in a classic position at the head of a high-fidelity simulation manikin, in weightlessness and in normogravity. Neither of the two tested conditions reached the minimal terrestrial ILCOR recommendations (95% first-pass success) and therefore could not be recommended for general implementation under weightlessness conditions. Free-floating video laryngoscopy at the head of the manikin had a significant better success score than conventional direct laryngoscopy in an ice-pick position. Our results, combined with the preexisting literature, emphasis the difficulties of performing oro-tracheal intubation, even for experts using modern airway devices, under postural instability in weightlessness. ClinicalTrials registration number NCT05303948.

Introduction Supplemental oxygen is commonly used in trauma patients, although it may lead to hyperoxaemia that has been associated with pulmonary complications and increased mortality. The primary objective of this trial, TRAUMOX2, is to compare a restrictive versus liberal oxygen strategy the first 8 hours following trauma.Methods and analysis TRAUMOX2 is an investigator-initiated, international, parallel-grouped, superiority, outcome assessor-blinded and analyst-blinded, randomised, controlled, clinical trial.Adult patients with suspected major trauma are randomised to eight hours of a restrictive or liberal oxygen strategy. The restrictive group receives the lowest dosage of oxygen (>21%) that ensures an SpO2 of 94%. The liberal group receives 12–15 L O2/min or FiO2=0.6–1.0.The primary outcome is a composite of 30-day mortality and/or development of major respiratory complications (pneumonia and/or acute respiratory distress syndrome).With 710 participants in each arm, we will be able to detect a 33% risk reduction with a restrictive oxygen strategy if the incidence of our primary outcome is 15% in the liberal group.Ethics and dissemination TRAUMOX2 is carried out in accordance with the Helsinki II Declaration. It has been approved by the Danish Committee on Health Research Ethics for the Capital Region (H-21018062) and The Danish Medicines Agency, as well as the Dutch Medical Research Ethics Committee Erasmus MS (NL79921.078.21 and MEC-2021-0932). A website (www.traumox2.org) is available for updates and study results will be published in an international peer-reviewed scientific journal.Trial registration numbers EudraCT 2021-000556-19; NCT05146700.

Abstract In the next few years, the number of long-term space missions will significantly increase. Providing safe concepts for emergencies including airway management will be a highly challenging task. The aim of the present trial is to compare different airway management devices in simulated microgravity using a free-floating underwater scenario. Five different devices for airway management [laryngeal mask (LM), laryngeal tube (LT), I-GEL, direct laryngoscopy (DL), and video laryngoscopy (VL)] were compared by n = 20 paramedics holding a diving certificate in a randomized cross-over setting both under free-floating conditions in a submerged setting (pool, microgravity) and on ground (normogravity). The primary endpoint was the successful placement of the airway device. The secondary endpoints were the number of attempts and the time to ventilation. A total of 20 paramedics (3 female, 17 male) participated in this study. Success rate was highest for LM and LT and was 100% both during simulated microgravity and normogravity followed by the I-GEL (90% during microgravity and 95% during normogravity). However, the success rate was less for both DL (60% vs. 95%) and VL (20% vs. 60%). Fastest ventilation was performed with the LT both in normogravity (13.7 ± 5.3 s; n = 20) and microgravity (19.5 ± 6.1 s; n = 20). For the comparison of normogravity and microgravity, time to ventilation was shorter for all devices on the ground (normogravity) as compared underwater (microgravity). In the present study, airway management with supraglottic airways and laryngoscopy was shown to be feasible. Concerning the success rate and time to ventilation, the optimum were supraglottic airways (LT, LM, I-GEL) as their placement was faster and associated with a higher success rate. For future space missions, the use of supraglottic airways for airway management seems to be more promising as compared to tracheal intubation by DL or VL.

Abstract Background Mechanical ventilation in helicopter emergency medical service (HEMS) environments is a procedure which carries a significant risk of complications. Limited data on the quality and performance of mechanical ventilation in HEMS are available in the literature. Method We conducted an international survey to evaluate mechanical ventilation infrastructure in HEMS and collect data of transported ventilated patients. From June 20–22, 2019, the participating HEMS bases were asked to provide data via a web-based platform. Vital parameters and ventilation settings of the patients at first patient contact and at handover were compared using non-parametric statistical tests. Results Out of 215 invited HEMS bases, 53 responded. Respondents were from Germany, Denmark, United Kingdom, Luxembourg, Austria and Switzerland. Of the HEMS bases, all teams were physician staffed, mainly anesthesiologists (79%), the majority were board certified (92.5%) and trained in intensive care medicine (89%) and had a median (range) experience in HEMS of 9 (0–25) years. HEMS may provide a high level of expertise in mechanical ventilation whereas the majority of ventilators are able to provide pressure controlled ventilation and continuous positive airway pressure modes (77%). Data of 30 ventilated patients with a median (range) age of 54 (21–100) years and 53% male gender were analyzed. Of these, 24 were primary missions and 6 interfacility transports. At handover, oxygen saturation (p

Abstract Background With the “Artemis”-mission mankind will return to the Moon by 2024. Prolonged periods in space will not only present physical and psychological challenges to the astronauts, but also pose risks concerning the medical treatment capabilities of the crew. So far, no guideline exists for the treatment of severe medical emergencies in microgravity. We, as a international group of researchers related to the field of aerospace medicine and critical care, took on the challenge and developed a an evidence-based guideline for the arguably most severe medical emergency – cardiac arrest. Methods After the creation of said international group, PICO questions regarding the topic cardiopulmonary resuscitation in microgravity were developed to guide the systematic literature research. Afterwards a precise search strategy was compiled which was then applied to “MEDLINE”. Four thousand one hundred sixty-five findings were retrieved and consecutively screened by at least 2 reviewers. This led to 88 original publications that were acquired in full-text version and then critically appraised using the GRADE methodology. Those studies formed to basis for the guideline recommendations that were designed by at least 2 experts on the given field. Afterwards those recommendations were subject to a consensus finding process according to the DELPHI-methodology. Results We recommend a differentiated approach to CPR in microgravity with a division into basic life support (BLS) and advanced life support (ALS) similar to the Earth-based guidelines. In immediate BLS, the chest compression method of choice is the Evetts-Russomano method (ER), whereas in an ALS scenario, with the patient being restrained on the Crew Medical Restraint System, the handstand method (HS) should be applied. Airway management should only be performed if at least two rescuers are present and the patient has been restrained. A supraglottic airway device should be used for airway management where crew members untrained in tracheal intubation (TI) are involved. Discussion CPR in microgravity is feasible and should be applied according to the Earth-based guidelines of the AHA/ERC in relation to fundamental statements, like urgent recognition and action, focus on high-quality chest compressions, compression depth and compression-ventilation ratio. However, the special circumstances presented by microgravity and spaceflight must be considered concerning central points such as rescuer position and methods for the performance of chest compressions, airway management and defibrillation.

Abstract Background Blood products are a lifesaving commodity in the treatment of major trauma. Although there is little evidence for use of pre-hospital blood products (PHBP) in seriously injured patients, an increasing number of emergency medical services have started using PHBP for treatment of major haemorrhage. The primary aim of this survey was to establish the degree of prehospital blood product use throughout Europe and discover main indications. The secondary aim was to evaluate opinions about PHBP and also the experience and the personal views of its users. Methods The subcommittee for Critical Emergency Medicine of the European Society of Anaesthesiology (ESA) held an online survey of European Helicopter Emergency Services (HEMS) and all French Services d’Aide Médicale Urgente (SAMU) regions. It contained 13 questions both open and multiple-choice about the frequency transfusions are carried out, the PHBP used and the perceived benefit. The survey was distributed to the corresponding HEMS leads in 14 European countries. Results In total there were 172 valid responses; overall 48% of all respondents have prehospital access to packed red cells, 22% to fresh plasma and 14% use lyophilised plasma. Besides blood product administration, 94% of all services use tranexamic acid. Sixty five percent of all replies came from French and from German services (37 and 28% respectively). PHBP were mainly used for trauma related emergencies. France has the highest uptake of use of blood products at 89%, whereas the rate in Germany was far lower at 6%. Fifty five percent of the service leads felt that PHBP are beneficial, and even lifesaving in individual cases despite being needed infrequently. Conclusions We found remarkable dissimilarities in practice between the different European countries. Even if there is not an absolute consensus amongst providers on the benefit of PHBP, the majority feel they are beneficial. The difference in practice is possibly related to the perceived lack of evidence on prehospital blood transfusion. We suggest to include the use of PHBP in trauma registries in order to consolidate the existing evidence.

BackgroundResveratrol may improve organ dysfunction after experimental hemorrhagic or septic shock, and some of these effects appear to be mediated by estrogen receptors. However, the influence of resveratrol on liver function and hepatic microcirculation after hemorrhagic shock is unknown, and a presumed mediation via estrogen receptors has not been investigated in this context.MethodsMale Sprague-Dawley rats (200-300g, n = 14/group) underwent hemorrhagic shock for 90 min (MAP 35±5 mmHg) and were resuscitated with shed blood and Ringer's solution. Animals were treated intravenously with vehicle (1% EtOH), resveratrol (0.2 mg/kg), the unselective estrogen receptor antagonist ICI 182,780 (0.05 mg/kg) or resveratrol + ICI 182,780 prior to retransfusion. Sham-operated animals did not undergo hemorrhage but were treated likewise. After 2 hours of reperfusion, liver function was assessed either by plasma disappearance rate of indocyanine green (PDRICG) or evaluation of hepatic perfusion and hepatic integrity by intravital microscopy, serum enzyme as well as cytokine levels.ResultsCompared to vehicle controls, administration of resveratrol significantly improved PDRICG, hepatic perfusion index and hepatic integrity after hemorrhagic shock. The co-administration of ICI 182,780 completely abolished the protective effect only with regard to liver function.ConclusionsThis study shows that resveratrol may improve liver function and hepatocellular integrity after hemorrhagic shock in rats; estrogen receptors mediate these effects at least partially.

The sensitivity of human immune system cells to gravity changes has been investigated in numerous studies. Human macrophages mediate innate and thus rapid immune defense on the one hand and activate T- and B-cell-based adaptive immune response on the other hand. In this process they finally act as immunoeffector cells, and are essential for tissue regeneration and remodeling. Recently, we demonstrated in the human Jurkat T cell line that genes are differentially regulated in cluster structures under altered gravity. In order to study an in vivo near system of immunologically relevant human cells under physically real microgravity, we performed parabolic flight experiments with primary human M1 macrophages under highly standardized conditions and performed chromatin immunoprecipitation DNA sequencing (ChIP-Seq) for whole-genome epigenetic detection of the DNA-binding loci of the main transcription complex RNA polymerase II and the transcription-associated epigenetic chromatin modification H3K4me3. We identified an overall downregulation of H3K4me3 binding loci in altered gravity, which were unequally distributed inter- and intrachromosomally throughout the genome. Three-quarters of all affected loci were located on the p arm of the chromosomes chr5, chr6, chr9, and chr19. The genomic distribution of the downregulated H3K4me3 loci corresponds to a substantial extent to immunoregulatory genes. In microgravity, analysis of RNA polymerase II binding showed increased binding to multiple loci at coding sequences but decreased binding to central noncoding regions. Detection of altered DNA binding of RNA polymerase II provided direct evidence that gravity changes can lead to altered transcription. Based on this study, we hypothesize that the rapid transcriptional response to changing gravitational forces is specifically encoded in the epigenetic organization of chromatin.

(1) Background: Cardiopulmonary resuscitation (CPR), as a form of basic life support, is critical for maintaining cardiac and cerebral perfusion during cardiac arrest, a medical condition with high expected mortality. Current guidelines emphasize the importance of rapid recognition and prompt initiation of high-quality CPR, including appropriate cardiac compression depth and rate. As space agencies plan missions to the Moon or even to explore Mars, the duration of missions will increase and with it the chance of life-threatening conditions requiring CPR. The objective of this review was to examine the effectiveness and feasibility of chest compressions as part of CPR following current terrestrial guidelines under hypogravity conditions such as those encountered on planetary or lunar surfaces; (2) Methods: A systematic literature search was conducted by two independent reviewers (PubMed, Cochrane Register of Controlled Trials, ResearchGate, National Aeronautics and Space Administration (NASA)). Only controlled trials conducting CPR following guidelines from 2010 and after with advised compression depths of 50 mm and above were included; (3) Results: Four different publications were identified. All studies examined CPR feasibility in 0.38 G simulating the gravitational force on Mars. Two studies also simulated hypogravity on the Moon with a force of 0.17 G/0,16 G. All CPR protocols consisted of chest compressions only without ventilation. A compression rate above 100/s could be maintained in all studies and hypogravity conditions. Two studies showed a significant reduction of compression depth in 0.38 G (−7.2 mm/−8.71 mm) and 0.17 G (−12.6 mm/−9.85 mm), respectively, with nearly similar heart rates, compared to 1 G conditions. In the other two studies, participants with higher body weight could maintain a nearly adequate mean depth while effort measured by heart rate (+23/+13.85 bpm) and VO2max (+5.4 mL·kg−1·min−1) increased significantly; (4) Conclusions: Adequate CPR quality in hypogravity can only be achieved under increased physical stress to compensate for functional weight loss. Without this extra effort, the depth of compression quickly falls below the guideline level, especially for light-weight rescuers. This means faster fatigue during resuscitation and the need for more frequent changes of the resuscitator than advised in terrestrial guidelines. Alternative techniques in the straddling position should be further investigated in hypogravity.

Introduction: Since Gagarin became the first human to travel into space and complete one orbit around the Earth, on 12 April 1961, the number of manned spaceflights has increased significantly. Spaceflight is still complex and has potential risk for incidents and accidents. The aim of this study was to analyze how safe it is for humans to travel in space. Objectives: This paper, therefore, summarizes incidents and accidents covering the six decades of manned spaceflight (1961–2020). Material and methods: Extensive PubMed, Cochrane, and Google Scholar searches were made with search strings of “incidents”, “accident”, “spaceflight”, and “orbit”, and including all vehicles so far. Search terms were combined by AND or OR in search strings. Of the results obtained, studies which evaluated manned spaceflight were included in the study. Data from the National Aeronautics Space Agency (NASA), the Russian Space Agency (ROSCOSMOS), the European Space Agency (ESA), and the Chinese Space Agency (CNSA), as well as from the Virgin Galactic and the SpaceX databases, were searched to complete data and to identify all the accomplished manned spaceflights, as well as all incidents and accidents that have occurred in the specific period. Search results were compared to findings on Wikipedia, Encyclopedia Astronautica, and other public webpages. Reference lists of included articles/homepages were also included for further potential data. Results: From 1961–2020, our data revealed an increasing number of manned space flights, n = 327. The number of times an astronaut has been sent to space, n = 1294, resulted in an accumulated n = 19,414 days spent in space. The number of days spent in orbit has constantly increased from 1961 until today. The number of incidents (altogether n = 36) and accidents (altogether n = 5) has constantly decreased. The number of astronauts who have died during spaceflight is represented by n = 19. The current statistical fatality rate is 5.8% (deaths per spaceflight) with the highest fatality rate in the 1960s (0.013 deaths/day spent in space), and the lowest rates in the 1990s and the period from 2010 until the present (no deaths). The most dangerous phases of spaceflight are launch, landing and staying in orbit. Altogether, n = 12 incidents (incident rate per spaceflight: 0.04) and one accident (accident rate: 0.003) during launch have been reported, n = 9 incidents (incident rate: 0.03) and two accidents (accident rate: 0.006) have been reported during landing and n = 10 incidents (incident rate: 0.03) have been reported in orbit. Discussion: Manned spaceflight over the last six decades has become significantly safer. Since 2003, no astronaut fatality has been reported. With greater international cooperation and maintaining of the International Space Station (ISS), the number of manned spaceflights and days spent in space has constantly increased, with constantly lower rates of incidents and accidents.

Abstract Background Airway management is crucial and, probably, even the most important key competence in anaesthesiology, which directly influences patient safety and outcome. However, high-quality research is rarely published and studies usually have different primary or secondary endpoints which impedes clear unbiased comparisons between studies. The aim of the present study was to gather and analyse primary and secondary endpoints in video laryngoscopy studies being published over the last ten years and to create a core set of uniform or homogeneous outcomes (COS). Methods Retrospective analysis. Data were identified by using MEDLINE® database and the terms “video laryngoscopy” and “video laryngoscope” limited to the years 2007 to 2017. A total of 3351 studies were identified by the applied search strategy in PubMed. Papers were screened by two anaesthesiologists independently to identify study endpoints. The DELPHI method was used for consensus finding. Results In the 372 studies analysed and included, 49 different outcome categories/columns were reported. The items “time to intubation” (65.86%), “laryngeal view grade” (44.89%), “successful intubation rate” (36.56%), “number of intubation attempts” (23.39%), “complications” (21.24%), and “successful first-pass intubation rate” (19.09%) were reported most frequently. A total of 19 specific parameters is recommended. Conclusions In recent video laryngoscopy studies, many different and inhomogeneous parameters were used as outcome descriptors/endpoints. Based on these findings, we recommend that 19 specific parameters (e.g., “time to intubation” (inserting the laryngoscope to first ventilation), “laryngeal view grade” (C&L and POGO), “successful intubation rate”, etc.) should be used in coming research to facilitate future comparisons of video laryngoscopy studies.

The human body reacts to hypobaric hypoxia, e.g., during a stay at high altitude, with several mechanisms of adaption. Even short-time exposition to hypobaric hypoxia leads to complex adaptions. Proteomics facilitates the possibility to detect changes in metabolism due to changes in proteins. The present study aims to identify time-dependent changes in protein expression due to hypobaric hypoxia for 30 and 60 min at a simulated altitude of 15,000 ft. N = 80 male subjects were randomized and assigned into four different groups: 40 subjects to ground control for 30 (GC30) and 60 min (GC60) and 40 subjects to 15,000 ft for 30 (HH30) and 60 min (HH60). Subjects in HH30 and HH60 were exposed to hypobaric hypoxia in a pressure chamber (total pressure: 572 hPa) equivalent to 15,000 ft for 30 vs. 60 min, respectively. Drawn blood was centrifuged and plasma frozen (−80 °C) until proteomic analysis. After separation of high abundant proteins, protein expression was analyzed by 2-DIGE and MALDI-TOF. To visualize the connected signaling cascade, a bio-informatical network analysis was performed. The present study was approved by the ethical committee of the University of Cologne, Germany. The study registry number is NCT03823677. In comparing HH30 to GC30, a total of seven protein spots had a doubled expression, and 22 spots had decreased gene expression. In a comparison of HH60 to GC60, a total of 27 protein spots were significantly higher expressed. HH60, as compared to GC30, revealed that a total of 37 spots had doubled expression. Vice versa, 12 spots were detected, which were higher expressed in GC30 vs. HH60. In comparison to GC, HH60 had distinct differences in the number of differential protein spots (noticeably more proteins due to longer exposure to hypoxia). There are indicators that changes in proteins are dependent on the length of hypobaric hypoxia. Some proteins associated with hemostasis were differentially expressed in the 60 min comparison.

An amendment to this paper has been published and can be accessed via the original article.

Melatonin receptors are highly relevant for the hepatoprotective effects of the pineal hormone melatonin after experimental hemorrhagic shock in rats. In this study, we sought to determine the spatial expression pattern and a putative regulation of two melatonin receptors, membrane bound type 1 and 2 (MT1 and MT2), in the liver of rats. In a male rat model (Sprague Dawley) of hemorrhage and resuscitation, we investigated the gene expression and protein of MT1 and MT2 in rat liver by utilizing real-time quantitative polymerase chain reaction, a western blot analysis, and immunohistochemistry. Plasma melatonin content was measured by an enzyme-linked immunosorbent assay. Male rats underwent hemorrhage and were resuscitated with shed blood and a Ringer’s solution (n = 8 per group). After 90 min of hemorrhage, animals were given vehicle, melatonin, or ramelteon (each 1.0 mg/kg intravenously). Sham-operated controls did not undergo hemorrhage but were treated likewise. Plasma melatonin was significantly increased in all groups treated with melatonin and also after hemorrhagic shock. Only MT1, but not the MT2 messenger ribonucleic acid (mRNA) and protein, was detected in the rat liver. The MT1 protein was located in pericentral fields of liver lobules in sham-operated animals. After hemorrhagic shock and treatment with melatonin or ramelteon, the hepatic MT1 protein amount was significantly attenuated in all groups compared to sham controls (50% reduction; p < 0.001). With respect to MT1 mRNA, no significant changes were observed between groups (p = 0.264). Our results indicate that both endogenous melatonin exposure from hemorrhagic shock, as well as exogenous melatonin and ramelteon exposure, may attenuate melatonin receptors in rat hepatocytes, possibly by means of desensitization.

Administration of oxygen is one of the most common interventions in medicine. Previous research showed that differential regulated proteins could be linked to hyperoxia-associated signaling cascades in different tissues. However, it still remains unclear which signaling pathways are activated by hyperoxia. The present study analyses hyperoxia-induced protein alterations in lung, brain, and kidney tissue using a proteomic and bioinformatic approach. Pooled data of 36 Wistar rats exposed to hyperoxia were used. To identify possible hyperoxia biomarkers, and to evaluate the relationship between protein alterations in hyperoxia affected organs and blood, proteomics data from brain, lung, and kidney were analyzed. Functional network analyses (IPA®, PathwaysStudio®, and GENEmania®) in combination with hierarchical cluster analysis (Perseus®) was used to identify relevant pathways and key proteins. Data of 54 2D-gels with more than 2500 significantly regulated spots per gel were collected. Thirty-eight differentially expressed proteins were identified and consecutively analyzed by bioinformatic methods. Most differences between hyperoxia and normoxia (21 proteins up-regulated, 17 proteins down-regulated) were found immediately after hyperoxia (15 protein spots), followed by day 3 (13 spots), and day 7 (10 spots). A highly significant association with inflammation and the inflammatory response was found. Cell proliferation, oxidative stress, apoptosis and cell death as well as cellular functions were revealed to be affected. Three hours of hyperoxia resulted in significant alterations of protein expression in different organs (brain, lung, kidney) up to seven days after exposure. Further studies are required to interpret the relevance of protein alterations in signaling cascades during/after hyperoxia.

Hypobaric hypoxia (HH) during airline travel induces several (patho-) physiological reactions in the human body. Whereas severe hypoxia is investigated thoroughly, very little is known about effects of moderate or short-term hypoxia, e.g. during airline flights. The aim of the present study was to analyse changes in serum protein expression and activation of signalling cascades in human volunteers staying for 30 min in a simulated altitude equivalent to airline travel. After approval of the local ethics committee, 10 participants were exposed to moderate hypoxia (simulation of 2400 m or 8000 ft for 30 min) in a hypobaric pressure chamber. Before and after hypobaric hypoxia, serum was drawn, centrifuged, and analysed by two-dimensional gel electrophoresis (2-DIGE) and matrix-assisted laser desorption/ionization followed by time-of-flight mass spectrometry (MALDI-TOF). Biological functions of regulated proteins were identified using functional network analysis (GeneMania®, STRING®, and Perseus® software). In participants, oxygen saturation decreased from 98.1 ± 1.3% to 89.2 ± 1.8% during HH. Expression of 14 spots (i.e., 10 proteins: ALB, PGK1, APOE, GAPDH, C1QA, C1QB, CAT, CA1, F2, and CLU) was significantly altered. Bioinformatic analysis revealed an association of the altered proteins with the signalling cascades “regulation of haemostasis” (four proteins), “metabolism” (five proteins), and “leukocyte mediated immune response” (five proteins). Even though hypobaric hypoxia was short and moderate (comparable to an airliner flight), analysis of protein expression in human subjects revealed an association to immune response, protein metabolism, and haemostasis