PDF(Pubmed)
Abstract：
OBJECTIVE: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
摘要：
目的：肺移植仍然受到健康器官短缺的限制。与健康猪受体的交叉循环提供了持久的生理环境以恢复受损的供体肺。在临床应用中，等待肺移植的受体可以进行交叉循环以恢复受损的供体肺，实现最终的移植。我们的目的是评估呼吸道受损的受体猪耐受交叉循环和支持长期冷缺血的供体肺恢复的能力。
方法：将猪供体肺（n=6）在4°C下储存24小时，而受体猪（n=6）在交叉循环之前经历了胃吸入性损伤。纵向多尺度分析(血气，支气管镜检查,射线照相术,组织病理学,细胞因子定量）用于评估受体猪和体外肺的交叉循环。
结果：受者猪肺损伤导致持续，氧合受损（基线时PaO2/FiO2比值205±39mmHg与454±111mmHg）。射线照相,支气管镜,组织学评估显示双侧浸润，气道细胞因子升高，并显著恶化肺损伤评分。受体猪为体外肺提供了足够的代谢支持，以证明其功能得到了强大的改善（0小时，PaO2/FiO2138±28.2mmHg;24小时,539±156mmHg）。多尺度分析表明总体外观有所改善，曝气,24小时后体外肺部细胞再生。
结论：我们证明了急性损伤的受体猪耐受交叉循环，并能够恢复经过长时间冷藏的供体肺。这项概念验证研究支持对孤立性肺部疾病的接受者进行交叉循环的可行性，谁是这种临床应用的候选人。
方法：将猪供体肺（n=6）在4°C下储存24小时，而受体猪（n=6）在交叉循环之前经历了胃吸入性损伤。纵向多尺度分析(血气，支气管镜检查,射线照相术,组织病理学,细胞因子定量）用于评估受体猪和体外肺的交叉循环。
结果：受者猪肺损伤导致持续，氧合受损（基线时PaO2/FiO2比值205±39mmHg与454±111mmHg）。射线照相,支气管镜,组织学评估显示双侧浸润，气道细胞因子升高，并显著恶化肺损伤评分。受体猪为体外肺提供了足够的代谢支持，以证明其功能得到了强大的改善（0小时，PaO2/FiO2138±28.2mmHg;24小时,539±156mmHg）。多尺度分析表明总体外观有所改善，曝气,24小时后体外肺部细胞再生。
结论：我们证明了急性损伤的受体猪耐受交叉循环，并能够恢复经过长时间冷藏的供体肺。这项概念验证研究支持对孤立性肺部疾病的接受者进行交叉循环的可行性，谁是这种临床应用的候选人。
