• Panpan Chen, Julie Van Hassel, Meghan R Pinezich, Mohamed Diane, Maria R Hudock, Sarah R Kaslow, Olimpia P Gavaudan, Kenmond Fung, Mandy L Kain, Hermogenes Lopez, Anjali Saqi, Brandon A Guenthart, Ahmed E Hozain, Alexander Romanov, Matthew Bacchetta, and Gordana Vunjak-Novakovic.
• Department of Biomedical Engineering, Columbia University, New York, NY; Department of Surgery, Columbia University Medical Center, New York, NY.
• J. Thorac. Cardiovasc. Surg. 2024 May 1; 167 (5): e106e130e106-e130.

ObjectiveLung 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.MethodsSwine 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.ResultsRecipient 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.ConclusionsWe 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.Copyright © 2023 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

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