Lung-Mimetic Hydrofoam Sealant to Treat Pulmonary Air Leak.

Pulmonary air leak is the most common complication of lung surgery, contributing to post-operative morbidity in up to 60% of patients; yet, there is no reliable treatment. Available surgical sealants do not match the demanding deformation mechanics of lung tissue; and therefore, fail to seal air leak. To address this therapeutic gap, a sealant with structural and mechanical similarity to subpleural lung is designed, developed, and systematically evaluated. This "lung-mimetic" sealant is a hydrofoam material that has alveolar-like porous ultrastructure, lung-like viscoelastic properties (adhesive, compressive, tensile), and lung extracellular matrix-derived signals (matrikines) to support tissue repair. In biocompatibility testing, the lung-mimetic sealant shows minimal cytotoxicity and immunogenicity in vitro. Human primary monocytes exposed to sealant matrikines in vitro upregulate key genes (MARCO, PDGFB, VEGF) known to correlate with pleural wound healing and tissue repair in vivo. In rat and swine models of pulmonary air leak, this lung-mimetic sealant rapidly seals air leak and restores baseline lung mechanics. Altogether, these data indicate that the lung-mimetic sealant can effectively seal pulmonary air leak and promote a favorable cellular response in vitro.

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 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.

Predictors of Outcomes After Thoracic Surgery in Orthotopic Liver Transplant Recipients With Pleural Disease.

Orthotopic liver transplant (OLT) recipients are at high risk for postoperative pulmonary complications. We aim to determine factors associated with morbidity and mortality in OLT recipients that required thoracic surgery for pleural space complications. A retrospective review was performed of 42 patients who underwent thoracic surgery after OLT between 2005 and 2015. Preoperative data and postoperative outcomes were reviewed. Time to mortality was summarized using Kaplan-Meier curves. Outcomes associated with 30-day morbidity and mortality as well as long-term mortality were analyzed with univariate analysis. Between 2005 and 2015, 1735 OLTs were performed at our institution. We identified 42 patients who required thoracic surgery. Of these 42 OLT recipients, 33 patients required thoracic surgery for pleural space complications. The median interval between OLT and thoracic surgery for pleural space complications was 5.7 months (interquartile range 2.2-14.1). The most common surgical indications were chronic pleural effusion (n = 12, 36.4%) and empyema (n = 10, 30.3%). The most common thoracic operations were decortication and empyema evacuation. The 30-day morbidity was 69.7%. Bilirubin and empyema were significantly associated with 30-day morbidity (odds ratio [OR] = 2.3, P = 0.023; OR = 16.3, P = 0.015). The 30-day, 1-year, and 5-year mortality rates were 15.2%, 57.6%, and 70.2%, respectively. Vasopressor requirement was significantly associated with 30-day mortality (OR = 10.2, P = 0.031). The development of pleural space complications requiring surgery in OLT recipients suggests a poor prognosis. Hyperbilirubinemia and pleural space infections were associated with high postoperative morbidity in OLT recipients requiring thoracic surgery for pleural space complications.