Department of Biomedical Engineering, Columbia University, New York, NY; Department of Surgery, Columbia University Medical Center, New York, NY.
Department of Biomedical Engineering, Columbia University, New York, NY.
J Thorac Cardiovasc Surg. 2024 May;167(5):e106-e130. doi: 10.1016/j.jtcvs.2023.09.032. Epub 2023 Sep 21.
Lung transplantation remains limited by the shortage of healthy organs. Cross-circulation with a healthy swine recipient provides a durable physiologic environment to recover injured donor lungs. In a clinical application, a recipient awaiting lung transplantation could be placed on cross-circulation to recover damaged donor lungs, enabling eventual transplantation. Our objective was to assess the ability of recipient swine with respiratory compromise to tolerate cross-circulation and support recovery of donor lungs subjected to extended cold ischemia.
Swine donor lungs (n = 6) were stored at 4 °C for 24 hours while recipient swine (n = 6) underwent gastric aspiration injury before cross-circulation. Longitudinal multiscale analyses (blood gas, bronchoscopy, radiography, histopathology, cytokine quantification) were performed to evaluate recipient swine and extracorporeal lungs on cross-circulation.
Recipient swine lung injury resulted in sustained, impaired oxygenation (arterial oxygen tension/inspired oxygen fraction ratio 205 ± 39 mm Hg vs 454 ± 111 mm Hg at baseline). Radiographic, bronchoscopic, and histologic assessments demonstrated bilateral infiltrates, airway cytokine elevation, and significantly worsened lung injury scores. Recipient swine provided sufficient metabolic support for extracorporeal lungs to demonstrate robust functional improvement (0 hours, arterial oxygen tension/inspired oxygen fraction ratio 138 ± 28.2 mm Hg; 24 hours, 539 ± 156 mm Hg). Multiscale analyses demonstrated improved gross appearance, aeration, and cellular regeneration in extracorporeal lungs by 24 hours.
We demonstrate that acutely injured recipient swine tolerate cross-circulation and enable recovery of donor lungs subjected to extended cold storage. This proof-of-concept study supports feasibility of cross-circulation for recipients with isolated lung disease who are candidates for this clinical application.
肺移植仍然受到健康器官短缺的限制。与健康猪受者进行交叉循环可提供持久的生理环境,以恢复受损的供体肺。在临床应用中,可以将等待肺移植的受者置于交叉循环中,以恢复受损的供体肺,从而最终进行移植。我们的目的是评估呼吸功能受损的受者猪是否能够耐受交叉循环,并支持经过长时间冷缺血的供体肺的恢复。
在交叉循环前,将供体猪的肺(n=6)在 4°C 下储存 24 小时,同时受者猪(n=6)经历胃抽吸损伤。进行纵向多尺度分析(血气、支气管镜检查、放射学、组织病理学、细胞因子定量),以评估交叉循环中的受者猪和体外肺。
受者猪的肺损伤导致持续的氧合受损(动脉血氧分压/吸入氧分数比从基线时的 205±39mmHg 降至 454±111mmHg)。放射学、支气管镜和组织学评估显示双侧浸润、气道细胞因子升高和明显加重的肺损伤评分。受者猪为体外肺提供了足够的代谢支持,使体外肺的功能得到显著改善(0 小时时,动脉血氧分压/吸入氧分数比为 138±28.2mmHg;24 小时时,为 539±156mmHg)。多尺度分析显示,体外肺在 24 小时时外观、通气和细胞再生均有改善。
我们证明了急性损伤的受者猪能够耐受交叉循环,并使经过长时间冷储存的供体肺得以恢复。这项概念验证研究支持了对于患有孤立性肺病且适合这种临床应用的受者进行交叉循环的可行性。