Exposure to 100% Oxygen Abolishes the Impairment of Fracture Healing after Thoracic Trauma

<div><p>In polytrauma patients a thoracic trauma is one of the most critical injuries and an important trigger of post-traumatic inflammation. About 50% of patients with thoracic trauma are additionally affected by bone fractures. The risk for fracture malunion is considerably increased in such patients, the pathomechanisms being poorly understood. Thoracic trauma causes regional alveolar hypoxia and, subsequently, hypoxemia, which in turn triggers local and systemic inflammation. Therefore, we aimed to unravel the role of oxygen in impaired bone regeneration after thoracic trauma. We hypothesized that short-term breathing of 100% oxygen in the early post-traumatic phase ameliorates inflammation and improves bone regeneration. Mice underwent a femur osteotomy alone or combined with blunt chest trauma 100% oxygen was administered immediately after trauma for two separate 3 hour intervals. Arterial blood gas tensions, microcirculatory perfusion and oxygenation were assessed at 3, 9 and 24 hours after injury. Inflammatory cytokines and markers of oxidative/nitrosative stress were measured in plasma, lung and fracture hematoma. Bone healing was assessed on day 7, 14 and 21. Thoracic trauma induced pulmonary and systemic inflammation and impaired bone healing. Short-term exposure to 100% oxygen in the acute post-traumatic phase significantly attenuated systemic and local inflammatory responses and improved fracture healing without provoking toxic side effects, suggesting that hyperoxia could induce anti-inflammatory and pro-regenerative effects after severe injury. These results suggest that breathing of 100% oxygen in the acute post-traumatic phase might reduce the risk of poorly healing fractures in severely injured patients.</p></div

Biomechanical and μCT analysis of the fracture callus 21 days post-injury.

<p>(A-C) The binding stiffness, moment of inertia and the apparent Young’s modulus of the fracture callus were decreased following TXT, O₂ treatment abolished these effects. Data represent medians and quartiles. Specimen numbers for each group are depicted. *p<0.05, **p < 0.001.</p

Cytokine/chemokine concentrations in lung homogenates.

<p>Data represent medians and quartiles. Specimen numbers for each group are depicted.</p><p>*p < 0.05 and</p><p>**p < 0.01 vs F</p><p>#p < 0.05 vs. F+TXT.</p><p>Cytokine/chemokine concentrations in lung homogenates.</p

Cytokine/chemokine concentrations in blood plasma and tail moments.

<p>Data represent medians and quartiles. Specimen numbers for each group are depicted.</p><p>*p < 0.05 and</p><p>**p < 0.01 vs F</p><p>#p < 0.05 and</p><p>##p < 0.01 vs. F+TXT.</p><p>Cytokine/chemokine concentrations in blood plasma and tail moments.</p

Enriched Air Nitrox Breathing Reduces Venous Gas Bubbles after Simulated SCUBA Diving: A Double-Blind Cross-Over Randomized Trial

<div><p>Objective</p><p>To test the hypothesis whether enriched air nitrox (EAN) breathing during simulated diving reduces decompression stress when compared to compressed air breathing as assessed by intravascular bubble formation after decompression.</p><p>Methods</p><p>Human volunteers underwent a first simulated dive breathing compressed air to include subjects prone to post-decompression venous gas bubbling. Twelve subjects prone to bubbling underwent a double-blind, randomized, cross-over trial including one simulated dive breathing compressed air, and one dive breathing EAN (36% O₂) in a hyperbaric chamber, with identical diving profiles (28 msw for 55 minutes). Intravascular bubble formation was assessed after decompression using pulmonary artery pulsed Doppler.</p><p>Results</p><p>Twelve subjects showing high bubble production were included for the cross-over trial, and all completed the experimental protocol. In the randomized protocol, EAN significantly reduced the bubble score at all time points (cumulative bubble scores: 1 [0–3.5] vs. 8 [4.5–10]; P < 0.001). Three decompression incidents, all presenting as cutaneous itching, occurred in the air versus zero in the EAN group (P = 0.217). Weak correlations were observed between bubble scores and age or body mass index, respectively.</p><p>Conclusion</p><p>EAN breathing markedly reduces venous gas bubble emboli after decompression in volunteers selected for susceptibility for intravascular bubble formation. When using similar diving profiles and avoiding oxygen toxicity limits, EAN increases safety of diving as compared to compressed air breathing.</p><p>Trial Registration</p><p><a href="http://www.isrctn.com/ISRCTN31681480" target="_blank">ISRCTN 31681480</a></p></div

Intravascular bubble scores of two air dives.

<p>Intravascular bubble scores of two air dives.</p

Immunohistological stainings of fractured femurs for markers of inflammation, nitrosative stress and vascularization.

<p>Left panels are representative slides of mice with isolated fracture, middle panels of animals with additional TXT, and right panels of mice with fracture, TXT and O₂ treatment. Images indicate cortical bone proximal to the fracture gap and periosteal callus, macrophage staining show the marrow cavity. (A-C) Neutrophil staining 3 days post-injury, (D-F) macrophage staining on day 7, (G-L) IL-6 and IL-10 staining on day 7, and (M-R) nitrotyrosine and PECAM-1 staining on day 14. Scale bars: 100 μm.</p

Tissue composition of fracture calli 14 and 21 days after injury.

<p>Callus composition of mice 14 and 21 days post-injury. (A) Mice with TXT displayed significantly more cartilage in comparison to O₂ treated mice after 14 days. (B) Analysis after 21 days did not reveal intergroup differences. (C-E) Representative Safranin-O stained callus sections 14 days after injury. Markedly more cartilage (stained red) was observed in F+TXT mice compared to the other groups. TOT = total osseous tissue, Cg = cartilage, FT = fibrous tissue. Scale bars: 500 μm. Data represent medians and quartiles. Specimen numbers for each group are depicted. *p<0.05.</p

Table_1_Mental but no bio-physiological long-term habituation to repeated social stress: A study on soldiers and the influence of mission abroad.docx

Soldiers regularly participate in missions abroad and subjectively adapt to this situation. However, they have an increased lifetime cardiovascular risk compared to other occupational groups. To test the hypothesis that foreign deployment results in different stress habituation patterns, we investigated long-term psychological and bio-physiological stress responses to a repeated social stress task in healthy soldiers with and without foreign deployment. Ninety-one female and male soldiers from the BEST study (German armed forces deployment and stress) participated three times in the Trier Social Stress Test for groups (TSST-G) prior to, 6–8 weeks after and 1 year after the mission abroad and were compared to a control group without foreign deployment during the study period. They completed the State-Trait-Anxiety Inventory scale (STAI), the Primary Appraisal Secondary Appraisal questionnaire (PASA) and the Multidimensional Mood State Questionnaire (MDBF). Salivary cortisol and α-amylase, blood pressure, heart rate and heart rate variability were determined. Soldiers showed mental habituation over the three times with a significant decrease after the TSST-G in anxiousness (STAI) and cognitive stress appraisal (PASA), they were calmer and reported better mood (MDBF). Prior to the social stress part, the mood (MDBF) declined significantly. None of the biological and physiological markers showed any adaptation to the TSST-G. Mission abroad did not significantly influence any measured psychobiological marker when compared to soldiers without foreign deployment. Foreign deployment does not result in alterations in psychobiological social stress response patterns over 1 year after mission abroad which indicates that adaptation to acute social stress is highly maintained in healthy soldiers. The discrepancy between subjective perception and objective stress response has numerous clinical implications and should receive more attention.</p

Inclusion and randomization flow diagram.

<p>EAN = Enriched air nitrox.</p