Recovery of Extracorporeal Lungs Using Cross-Circulation with Injured Recipient Swine

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 prior to 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 (PaO2/FiO2 ratio 205 ± 39 mmHg versus 454 ± 111 mmHg 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, PaO2/FiO2 138 ± 28.2 mmHg; 24 hours, 539 ± 156 mmHg). 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.