LUNG PRESERVATION FOR TRANSPLANTATION

移植时的肺保存

• 批准号: 2219955
• 负责人: JOEL D COOPER
• 金额: $ 32.64万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-09-01 至 1996-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2219955
• 关键词: biopsy; cell adhesion molecules; cell cell interaction; diagnostic respiratory lavage; dogs; glucose metabolism; histopathology; immunocytochemistry; laboratory rabbit; laboratory rat; leukocytes; lung transplantation; monoclonal antibody; pulmonary surfactants; reperfusion; respiratory function; tumor necrosis factor alpha; vascular endothelium permeability

The long range goal of the proposed study is to facilitate successful lung transplantation by improving methods for lung preservation and improving early lung function following transplantation. Achievement of these goals would facilitate the logistics of organ retrieval and improve utilization of the current donor pool. Furthermore improved early graft function would reduce morbidity and mortality following lung transplantation. The research plan has two components: 1) To characterize alterations occurring in the lung during preservation with specific reference to vascular endothelium. This will involve analysis of functional changes (measurement of permeability) and alterations of vascular endothelial cell surface proteins (intercellular adhesion molecules) which play a role in leukocyte-mediated injury following reperfusion. 2) To explore the use of specific strategies to reduce or eliminate leukocyte-endothelial interactions following reperfusion. These interventions include the use of monoclonal antibodies against adhesion molecules; pharmacologic inhibition of neutrophil activation and cytokine release; and use of monoclonal antibodies directed against tumor necrosis factor, a cytokine which plays a major role in leukocyte-mediated injury.

拟议的研究的远距离目标是促进成功的肺 通过改善肺部保存和改进的方法来移植 移植后的早期肺功能。实现这些目标 将促进器官检索的物流并改善利用率 当前的捐助池。此外，提高了早期移植功能将 肺移植后降低发病率和死亡率。这 研究计划有两个组成部分：1）表征发生的变化 在保存过程中的肺中，具体参考血管 内皮。这将涉及对功能变化的分析（测量 渗透性）和血管内皮细胞表面的改变 蛋白质（细胞间粘附分子），在 再灌注后白细胞介导的损伤。 2）探索使用 减少或消除白细胞 - 内皮的特定策略 再灌注后的相互作用。 这些干预措施包括使用 抗粘附分子的单克隆抗体；药理学 抑制嗜中性粒细胞活化和细胞因子释放；并使用 针对肿瘤坏死因子的单克隆抗体，一种细胞因子 在白细胞介导的损伤中起主要作用。