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

Kemmler J, Bindl R, McCook O, Wagner F, Gröger M, Wagner K, Scheuerle A, Radermacher P, Ignatius A - PLoS ONE (2015)

Bottom Line: Inflammatory cytokines and markers of oxidative/nitrosative stress were measured in plasma, lung and fracture hematoma.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.

View Article: PubMed Central - PubMed

Affiliation: Institute of Orthopaedic Research and Biomechanics, Center of Musculoskeletal Research, University of Ulm, Ulm, Germany.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

Microscopic and molecular analyses of lungs.(A) Lung tissue expression of HO-1 3 and 9 hours post-injury. (B) Quantitative analysis of lung histology after 1, 3 and 21 d. (C) Histological scoring of neutrophil stainings in the lungs and (D-F) representative slides 3 hours after injury showing increased numbers of neutrophils after TXT; arrows highlight positively stained neutrophils. (G) Analysis of caspase-3 staining and (H-J) representative slides of each group, 3 hours after injury. Values of outliers: #1 = 7.7x104; #2 = 6.69x104; #3 = 5.7x104; #4 = 2.96x105; #5 = 4.07x105; #6 = 6.16x104. (K-N) Positive nitrotyrosine staining was detected up to 21 days after surgery. O2 treatment significantly decreased the level of nitrotyrosine. Scale bars: 50 μm; box-plots represent medians and quartiles, whiskers represent the minimum and maximum values. Data represent medians and quartiles. Specimen numbers for each group are depicted. *p<0.05, **p < 0.001.
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pone.0131194.g001: Microscopic and molecular analyses of lungs.(A) Lung tissue expression of HO-1 3 and 9 hours post-injury. (B) Quantitative analysis of lung histology after 1, 3 and 21 d. (C) Histological scoring of neutrophil stainings in the lungs and (D-F) representative slides 3 hours after injury showing increased numbers of neutrophils after TXT; arrows highlight positively stained neutrophils. (G) Analysis of caspase-3 staining and (H-J) representative slides of each group, 3 hours after injury. Values of outliers: #1 = 7.7x104; #2 = 6.69x104; #3 = 5.7x104; #4 = 2.96x105; #5 = 4.07x105; #6 = 6.16x104. (K-N) Positive nitrotyrosine staining was detected up to 21 days after surgery. O2 treatment significantly decreased the level of nitrotyrosine. Scale bars: 50 μm; box-plots represent medians and quartiles, whiskers represent the minimum and maximum values. Data represent medians and quartiles. Specimen numbers for each group are depicted. *p<0.05, **p < 0.001.

Mentions: To exclude possible toxic side effects of the O2 treatment, we tested whole blood samples for DNA-strand breaks using the alkaline comet assay. Tail moments did not show any significant intergroup or time-dependent differences. HO-1 expression did not differ either following thoracic trauma or O2 exposure 3 and 9 hours after surgery, indicating the absence of additional oxidative stress (Fig 1A).


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

Kemmler J, Bindl R, McCook O, Wagner F, Gröger M, Wagner K, Scheuerle A, Radermacher P, Ignatius A - PLoS ONE (2015)

Microscopic and molecular analyses of lungs.(A) Lung tissue expression of HO-1 3 and 9 hours post-injury. (B) Quantitative analysis of lung histology after 1, 3 and 21 d. (C) Histological scoring of neutrophil stainings in the lungs and (D-F) representative slides 3 hours after injury showing increased numbers of neutrophils after TXT; arrows highlight positively stained neutrophils. (G) Analysis of caspase-3 staining and (H-J) representative slides of each group, 3 hours after injury. Values of outliers: #1 = 7.7x104; #2 = 6.69x104; #3 = 5.7x104; #4 = 2.96x105; #5 = 4.07x105; #6 = 6.16x104. (K-N) Positive nitrotyrosine staining was detected up to 21 days after surgery. O2 treatment significantly decreased the level of nitrotyrosine. Scale bars: 50 μm; box-plots represent medians and quartiles, whiskers represent the minimum and maximum values. Data represent medians and quartiles. Specimen numbers for each group are depicted. *p<0.05, **p < 0.001.
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Related In: Results  -  Collection

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pone.0131194.g001: Microscopic and molecular analyses of lungs.(A) Lung tissue expression of HO-1 3 and 9 hours post-injury. (B) Quantitative analysis of lung histology after 1, 3 and 21 d. (C) Histological scoring of neutrophil stainings in the lungs and (D-F) representative slides 3 hours after injury showing increased numbers of neutrophils after TXT; arrows highlight positively stained neutrophils. (G) Analysis of caspase-3 staining and (H-J) representative slides of each group, 3 hours after injury. Values of outliers: #1 = 7.7x104; #2 = 6.69x104; #3 = 5.7x104; #4 = 2.96x105; #5 = 4.07x105; #6 = 6.16x104. (K-N) Positive nitrotyrosine staining was detected up to 21 days after surgery. O2 treatment significantly decreased the level of nitrotyrosine. Scale bars: 50 μm; box-plots represent medians and quartiles, whiskers represent the minimum and maximum values. Data represent medians and quartiles. Specimen numbers for each group are depicted. *p<0.05, **p < 0.001.
Mentions: To exclude possible toxic side effects of the O2 treatment, we tested whole blood samples for DNA-strand breaks using the alkaline comet assay. Tail moments did not show any significant intergroup or time-dependent differences. HO-1 expression did not differ either following thoracic trauma or O2 exposure 3 and 9 hours after surgery, indicating the absence of additional oxidative stress (Fig 1A).

Bottom Line: Inflammatory cytokines and markers of oxidative/nitrosative stress were measured in plasma, lung and fracture hematoma.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.

View Article: PubMed Central - PubMed

Affiliation: Institute of Orthopaedic Research and Biomechanics, Center of Musculoskeletal Research, University of Ulm, Ulm, Germany.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus