Lung remains the least-utilized solid organ for transplantation. Efforts to recover donor lungs with reversible injuries using ex vivo perfusion systems are limited to <24 hours of support. Here, we demonstrate the feasibility of extending normothermic extracorporeal lung support to 4 days using cross-circulation with conscious swine.
A swine behavioral training program and custom enclosure were developed to enable multiday cross-circulation between extracorporeal lungs and recipient swine. Lungs were ventilated and perfused in a normothermic chamber for 4 days. Longitudinal analyses of extracorporeal lungs (ie, functional assessments, multiscale imaging, cytokine quantification, and cellular assays) and recipient swine (eg, vital signs and blood and tissue analyses) were performed.
Throughout 4 days of normothermic support, extracorporeal lung function was maintained (arterial oxygen tension/inspired oxygen fraction >400 mm Hg; compliance >20 mL/cm H2O), and recipient swine were hemodynamically stable (lactate <3 mmol/L; pH, 7.42 ± 0.05). Radiography revealed well-aerated lower lobes and consolidation in upper lobes of extracorporeal lungs, and bronchoscopy showed healthy airways without edema or secretions. In bronchoalveolar lavage fluid, granulocyte-macrophage colony-stimulating factor, interleukin (IL) 4, IL-6, and IL-10 levels increased less than 6-fold, whereas interferon gamma, IL-1α, IL-1β, IL-1ra, IL-2, IL-8, IL-12, IL-18, and tumor necrosis factor alpha levels decreased from baseline to day 4. Histologic evaluations confirmed an intact blood–gas barrier and outstanding preservation of airway and alveolar architecture. Cellular viability and metabolism in extracorporeal lungs were confirmed after 4 days.
We demonstrate feasibility of normothermic maintenance of extracorporeal lungs for 4 days by cross-circulation with conscious swine. Cross-circulation approaches could support the recovery of damaged lungs and enable organ bioengineering to improve transplant outcomes… Continue reading.
Medical, surgical and technological advancements in organ transplantation continue to expand life-saving treatment options for patients with end-stage lung disease, but transplantation remains limited by the low availability of donor organs. As chronic respiratory disease is the third-leading cause of death worldwide1, the need for innovative solutions to reduce associated morbidity and mortality is imperative. In 2020, lung transplantation remains the only definitive cure for end-stage lung disease, which has poor prognosis due to disease severity, insufficient donor lung availability and high rates of chronic allograft dysfunction. Strategies to increase organ supply involve utilizing extended criteria lungs, developing new technologies to recover donor lungs for transplantation and generating transplantable organs from xenogeneic sources, such as genetically engineered swine. Currently, the most utilized approach is to recover standard and extended criteria lungs by normothermic EVLP9. However, evidence of cellular regeneration in injured human lungs has not been robustly demonstrated in EVLP studies. To increase the quality and duration of extracorporeal lung support and investigate the potential for cellular regeneration, our group previously reported the development of an organ support platform in a swine model. While EVLP of healthy swine lungs perfused with whole blood has been reported, a study of injured swine lungs placed on EVLP with whole blood demonstrated insufficient recovery and resulted in impaired oxygenation and poor performance after transplantation13. In contrast, cross-circulation of severely injured swine lungs with a swine host enabled substantial cellular regeneration and functional recovery. Unlike EVLP systems, cross-circulation provides extracorporeal lungs with complete systemic support, including hepatic, pancreatic, renal and neurohormonal regulation, thereby enabling robust maintenance of healthy lungs outside the body for 4d… Continue reading....
WASHINGTON, D.C. — The American Institute for Medical and Biological Engineering (AIMBE) has announced the induction of Matthew Bacchetta, MD, H. William Scott, Jr Chair in Surgery and Associate Professor, Thoracic & Cardiac Surgery/Surgical Sciences, Vanderbilt University Medical Center, to its College of Fellows.
Election to the AIMBE College of Fellows is among the highest professional distinctions accorded to a medical and biological engineer. The College of Fellows is comprised of the top two percent of medical and biological engineers. College membership honors those who have made outstanding contributions to “engineering and medicine research, practice, or education” and to “the pioneering of new and developing fields of technology, making major advancements in traditional fields of medical and biological engineering, or developing/implementing innovative approaches to bioengineering education.”
Dr. Bacchetta was nominated, reviewed, and elected by peers and members of the College of Fellows for “seminal contributions to the fields of organ transplantation and organ regeneration and engineering.“...