Büren Carina, Lögters Tim, Oezel Lisa, Rommelfanger Golnessa, Scholz Armin Olaf, Windolf Joachim, Windolf Ceylan Daniela
Department for Trauma- and Hand Surgery, Medical Faculty, Heinrich-Heine-University, Düsseldorf Moorenstraße 5, Düsseldorf, Germany.
PLoS One. 2018 Jan 29;13(1):e0191594. doi: 10.1371/journal.pone.0191594. eCollection 2018.
Hyperbaric oxygen therapy (HBO) is applied very successfully in treatment of various diseases such as chronic wounds. It has been already suggested as adjunctive treatment option for osteitis by immune- and fracture modulating effects. This study evaluates the importance of HBO in an early implant-associated localized osteitis caused by Staphylococcus aureus (SA) compared to the standard therapy. In a standardized murine model the left femur of 120 BALB/c mice were osteotomized and fixed by a titanium locking plate. Osteitis has been induced with a defined amount of SA into the fracture gap. Debridément and lavages were progressed on day 7, 14, 28 and 56 to determine the local bacterial growth and the immune reaction. Hyperbaric oxygen (2 ATA, 90%) was applied for 90 minutes on day 7 to 21 for those mice allocated to HBO therapy. To evaluate the effect of HBO therapy the following groups were analyzed: Two sham-groups (12 mice / group) with and without HBO therapy, two osteotomy groups (24 mice / group) with plate osteosynthesis of the femur with and without HBO therapy, and two osteotomy SA infection groups (24 mice / group) with and without HBO therapy. Fracture healing was also quantified on day 7, 14, 28 and 56 by a.p. x-ray and bone healing markers from blood samples. Progression of infection was assessed by estimation of colony-forming units (CFU) and immune response was analyzed by determination of polymorphonuclear neutrophils (PMN), Interleukin (IL) - 6, and the circulating free DNA (cfDNA) in lavage samples. Osteitis induced significantly higher IL-6, cfDNA- and PMN-levels in the lavage samples (on day 7 and 14, each p < 0.05). HBO-therapy did not have a significant influence on the CFU and immune response compared to the standard therapy (each p > 0.05). At the same time HBO-therapy was associated with a delayed bone healing assessed by x-ray radiography and a higher rate of non-union until day 28. In conclusion, osteitis led to significantly higher bacterial count and infection parameters. HBO-therapy neither had a beneficial influence on local infection nor on immune response or fracture healing compared to the standard therapy in an osteitis mouse model.
高压氧疗法(HBO)在治疗各种疾病如慢性伤口方面应用非常成功。它已被建议作为通过免疫调节和骨折调节作用治疗骨髓炎的辅助治疗选择。本研究评估了与标准治疗相比,HBO在由金黄色葡萄球菌(SA)引起的早期植入物相关局限性骨髓炎中的重要性。在标准化的小鼠模型中,对120只BALB/c小鼠的左股骨进行截骨,并通过钛锁定板固定。将一定量的SA注入骨折间隙以诱导骨髓炎。在第7、14、28和56天进行清创和冲洗,以确定局部细菌生长和免疫反应。对于分配到HBO治疗组的小鼠,在第7天至21天给予90分钟的高压氧(2ATA,90%)。为了评估HBO治疗的效果,分析了以下几组:两个假手术组(每组12只小鼠),分别接受和不接受HBO治疗;两个截骨组(每组24只小鼠),分别进行股骨钢板内固定并接受和不接受HBO治疗;以及两个截骨SA感染组(每组24只小鼠),分别接受和不接受HBO治疗。在第7、14、28和56天,通过前后位X线片和血液样本中的骨愈合标志物对骨折愈合情况进行量化。通过估计菌落形成单位(CFU)评估感染进展,并通过测定灌洗样本中的多形核中性粒细胞(PMN)、白细胞介素(IL)-6和循环游离DNA(cfDNA)分析免疫反应。骨髓炎在灌洗样本中显著提高了IL-6、cfDNA和PMN水平(在第7天和14天,p均<0.05)。与标准治疗相比,HBO治疗对CFU和免疫反应没有显著影响(p均>0.05)。同时,通过X线摄影评估,HBO治疗与延迟的骨愈合相关,并且直到第28天不愈合率更高。总之,骨髓炎导致细菌计数和感染参数显著升高。在骨髓炎小鼠模型中,与标准治疗相比,HBO治疗对局部感染、免疫反应或骨折愈合均无有益影响。