University Hospital Essen, University Duisburg-Essen, Department of Thoracic and Cardiovascular Surgery, Thoracic Transplantation, West German Heart and Vascular Center, Essen, Germany; University Hospital Essen, University Duisburg-Essen, Institute of Molecular Biology, Essen, Germany.
University Hospital Essen, University Duisburg-Essen, Institute of Molecular Biology, Essen, Germany.
J Heart Lung Transplant. 2024 Jan;43(1):100-110. doi: 10.1016/j.healun.2023.08.021. Epub 2023 Sep 4.
Ex vivo lung perfusion (EVLP) has expanded the donor pool for lung transplantation. Pulmonary Staphylococcus aureus infection, especially that caused by multidrug-resistant strains, is a severe threat to posttransplantation outcomes. Sphingosine is a lipid compound that exhibits broad-spectrum antibacterial activity. Therefore, we aimed to evaluate the effects of S aureus infection on EVLP and whether sphingosine administration during EVLP prevents infection with S aureus.
Eighteen pigs were randomly assigned to 3 groups: uninfected, infected with S aureus with NaCl treatment, or infected with sphingosine treatment. Bacterial numbers were determined before and after treatment. Sphingosine concentrations in the lung tissues were determined using biochemical assays. Lung histology, lung physiological parameters, perfusate content, lung weight, and cell death were measured to analyze the effects of infection and sphingosine administration on EVLP.
Sphingosine administration significantly reduced the bacterial load. The concentration of sphingosine in the bronchial epithelium was elevated after sphingosine administration. S aureus infection increased pulmonary artery pressure and pulmonary vascular resistance. Lung edema, histology scores, lactate and lactate dehydrogenase levels in the perfusate, ΔPO in the perfusate, static lung compliance, and lung peak airway pressure did not differ among the groups.
Infection of S aureus did not affect the lung function during EVLP but induced higher pulmonary artery pressure and pulmonary vascular resistance. Administration of sphingosine effectively eliminated S aureus without side effects in isolated, perfused, and ventilated pig lungs.
体外肺灌注 (EVLP) 扩大了肺移植的供体池。金黄色葡萄球菌感染，尤其是耐多药菌株引起的感染，对移植后的结果构成了严重威胁。神经鞘氨醇是一种具有广谱抗菌活性的脂质化合物。因此，我们旨在评估金黄色葡萄球菌感染对 EVLP 的影响，以及 EVLP 期间施用神经鞘氨醇是否可以预防金黄色葡萄球菌感染。
将 18 头猪随机分为 3 组：未感染组、金黄色葡萄球菌感染+NaCl 处理组和金黄色葡萄球菌感染+神经鞘氨醇处理组。治疗前后测定细菌数量。采用生化测定法测定肺组织中的神经鞘氨醇浓度。测量肺组织学、肺生理参数、灌洗液含量、肺重量和细胞死亡，以分析感染和神经鞘氨醇给药对 EVLP 的影响。
神经鞘氨醇给药可显著降低细菌负荷。神经鞘氨醇给药后支气管上皮中的神经鞘氨醇浓度升高。金黄色葡萄球菌感染增加肺动脉压和肺血管阻力。肺水肿、灌洗液中的组织学评分、乳酸和乳酸脱氢酶水平、灌洗液中的ΔPO、静态肺顺应性和肺峰气道压在各组之间无差异。
金黄色葡萄球菌感染不会影响 EVLP 期间的肺功能，但会引起更高的肺动脉压和肺血管阻力。在离体、灌注和通气的猪肺中，施用神经鞘氨醇可有效消除金黄色葡萄球菌，且无副作用。
