Explore the vast range of titles available.

The number of available donor organs limits lung transplantation, the only lifesaving therapy for the increasing population of patients with end-stage lung disease. A prevalent etiology of injury that renders lungs unacceptable for transplantation is gastric aspiration, a deleterious insult to the pulmonary epithelium. Currently, severely damaged donor lungs cannot be salvaged with existing devices or methods. Here we report the regeneration of severely damaged lungs repaired to meet transplantation criteria by utilizing an interventional cross-circulation platform in a clinically relevant swine model of gastric aspiration injury. Enabled by cross-circulation with a living swine, prolonged extracorporeal support of damaged lungs results in significant improvements in lung function, cellular regeneration, and the development of diagnostic tools for non-invasive organ evaluation and repair. We therefore propose that the use of an interventional cross-circulation platform could enable recovery of otherwise unsalvageable lungs and thus expand the donor organ pool. Gastric aspiration severely injures donor lungs, frequently making them unacceptable for transplantation. Here the authors show that an interventional cross-circulation platform enables the regeneration of severely damaged lungs in a swine model of gastric aspiration injury.

The shortage of transplantable donor organs has profound consequences, especially for patients with end-stage lung disease, for which transplantation remains the only definitive treatment. Although advances in ex vivo lung perfusion have enabled the evaluation and reconditioning of marginally unacceptable donor lungs, clinical use of the technique is limited to ~6 h. Extending the duration of extracorporeal organ support from hours to days would enable longer recovery and recipient-specific manipulations of the donor lung, with the goal of expanding the donor organ pool and improving long-term outcomes. By using a clinically relevant swine model, here we report the development of a cross-circulation platform wherein recipient support enabled 36 h of normothermic perfusion that maintained healthy lungs and allowed for the recovery of injured lungs. Extended support enabled multiscale therapeutic interventions in all extracorporeal lungs. Lungs exceeded transplantation criteria, and recipients tolerated cross-circulation with no significant changes in physiologic parameters throughout 36 h of support. Our findings suggest that cross-circulation should enable extended support and interventions in extracorporeal organs. An extracorporeal cross-circulation approach enables, in a swine model, 36 hours of normothermic perfusion in healthy lungs, the recovery of injured lungs, and extended therapeutic interventions in all lungs.

Patients awaiting lung transplantation face high wait-list mortality, as injury precludes the use of most donor lungs. Although ex vivo lung perfusion (EVLP) is able to recover marginal quality donor lungs, extension of normothermic support beyond 6 h has been challenging. Here we demonstrate that acutely injured human lungs declined for transplantation, including a lung that failed to recover on EVLP, can be recovered by cross-circulation of whole blood between explanted human lungs and a Yorkshire swine. This xenogeneic platform provided explanted human lungs a supportive, physiologic milieu and systemic regulation that resulted in functional and histological recovery after 24 h of normothermic support. Our findings suggest that cross-circulation can serve as a complementary approach to clinical EVLP to recover injured donor lungs that could not otherwise be utilized for transplantation, as well as a translational research platform for immunomodulation and advanced organ bioengineering. In a new strategy for increasing the availability of lungs for transplantation, human lungs declined for transplantation because of their poor quality can be recuperated by connecting them to the circulation of a pig.

Donation after circulatory death (DCD) criteria serves as a potential strategy to expand the organ pool for heart transplantation. However, DCD procurement introduces prolonged warm ischemic times that accelerate endothelial and cardiomyocyte injury. Hypothermic oxygenated perfusion (HOPE) has emerged as a novel metabolic preservation strategy, yet its biological mechanisms remain undefined. We investigated how extended HOPE preservation modulates cardiomyocyte viability and metabolic stability after DCD in a porcine model. Following induced circulatory arrest and reperfusion with normothermic regional perfusion (NRP), porcine hearts were preserved either by static cold storage (SCS) for 2 h or by HOPE for 24 h. A third experimental group included hearts that were directly procured without NRP and preserved by HOPE for 2 h. All hearts were subsequently reperfused and reanimated using an extracorporeal circuit under normothermic conditions. Flow cytometry revealed measurable populations of troponin-positive viable cardiomyocytes even after 24-hour HOPE, in contrast to complete loss after 24-hour SCS. RNA sequencing and metabolomics demonstrated minimal transcriptional or metabolic shift between 2-hour SCS and 24-hour HOPE hearts, with preservation of oxidative and glycolytic balance and limited inflammatory activation. Furthermore, omission of NRP during procurement resulted in marked loss of contractility and cardiomyocyte integrity, underscoring its potential role in pre-preservation harvest in a porcine model. In a swine model extended hypothermic oxygenated perfusion preservation sustains myocardial and metabolic integrity after circulatory death by minimizing transcriptional and metabolic injury signatures.