Instantly adhesive and ultra-elastic patches for dynamic organ and wound repair.

Bioadhesive materials and patches are promising alternatives to surgical sutures and staples. However, many existing bioadhesives do not meet the functional requirements of current surgical procedures and interventions. Here, we present a translational patch material that exhibits instant adhesion to tissues (2.5-fold stronger than Tisseel, an FDA-approved fibrin glue), ultra-stretchability (stretching to >300% its original length without losing elasticity), compatibility with rapid photo-projection (<2 min fabrication time/patch), and ability to deliver therapeutics. Using our established procedures for the in silico design and optimization of anisotropic-auxetic patches, we created next-generation patches for instant attachment to tissues while conforming to a broad range of organ mechanics ex vivo and in vivo. Patches coated with extracellular vesicles derived from mesenchymal stem cells demonstrate robust wound healing capability in vivo without inducing a foreign body response and without the need for patch removal that can cause pain and bleeding. We further demonstrate a single material-based, void-filling auxetic patch designed for the treatment of lung puncture wounds.

Design Optimization and Tradeoff Analysis of an Actuated Continuum Probe for Pulmonary Nodule Localization and Resection.

Pulmonary nodules are abnormal tissue masses in the lungs, typically less than 3.0 cm in diameter, commonly detected during imaging of the chest and lungs. While most pulmonary nodules are not cancerous, surgical resection may be required if growth is detected between scans. This resection is typically performed without the benefit of intraoperative imaging, making it difficult for surgeons to confidently provide appropriate margins. To enhance the efficacy of wedge resection, researchers have developed a modified ultrasound imaging approach that utilizes both multiple scattering (MS) and single scattering (SS) to enhance the accuracy of margin delineation. Clinical deployment of this novel ultrasound technology requires a highly maneuverable ultrasound probe, ideally one that could be deployed and actuated with minimal invasiveness. This study details the design optimization and tradeoff analysis of an actuated continuum probe for pulmonary nodule localization and resection. This device, deployed through intercostal ports, would enable the intraoperative imaging and precise mapping of nodules for improved margin delineation and patient outcomes. To achieve this objective, multiple objective genetic algorithms (MOGAs) and a design of experiments (DOE) study are used to explore the design space and quantify key dimensional relationships and their effects on probe actuation.

Outcomes Following Lung Transplant for COVID-19-Related Complications in the US.

Importance: The COVID-19 pandemic led to the use of lung transplant as a lifesaving therapy for patients with irreversible lung injury. Limited information is currently available regarding the outcomes associated with this treatment modality. Objective: To describe the outcomes following lung transplant for COVID-19-related acute respiratory distress syndrome or pulmonary fibrosis. Design, Setting, and Participants: In this cohort study, lung transplant recipient and donor characteristics and outcomes following lung transplant for COVID-19-related acute respiratory distress syndrome or pulmonary fibrosis were extracted from the US United Network for Organ Sharing database from March 2020 to August 2022 with a median (IQR) follow-up period of 186 (64-359) days in the acute respiratory distress syndrome group and 181 (40-350) days in the pulmonary fibrosis group. Overall survival was calculated using the Kaplan-Meier method. Cox proportional regression models were used to examine the association of certain variables with overall survival. Exposures: Lung transplant following COVID-19-related acute respiratory distress syndrome or pulmonary fibrosis. Main Outcomes and Measures: Overall survival and graft failure rates. Results: Among 385 included patients undergoing lung transplant, 195 had COVID-19-related acute respiratory distress syndrome (142 male [72.8%]; median [IQR] age, 46 [38-54] years; median [IQR] allocation score, 88.3 [80.5-91.1]) and 190 had COVID-19-related pulmonary fibrosis (150 male [78.9%]; median [IQR] age, 54 [45-62]; median [IQR] allocation score, 78.5 [47.7-88.3]). There were 16 instances of acute rejection (8.7%) in the acute respiratory distress syndrome group and 15 (8.6%) in the pulmonary fibrosis group. The 1-, 6-, and 12- month overall survival rates were 0.99 (95% CI, 0.96-0.99), 0.95 (95% CI, 0.91-0.98), and 0.88 (95% CI, 0.80-0.94) for the acute respiratory distress syndrome cohort and 0.96 (95% CI, 0.92-0.98), 0.92 (95% CI, 0.86-0.96), and 0.84 (95% CI, 0.74-0.90) for the pulmonary fibrosis cohort. Freedom from graft failure rates were 0.98 (95% CI, 0.96-0.99), 0.95 (95% CI, 0.90-0.97), and 0.88 (95% CI, 0.79-0.93) in the 1-, 6-, and 12-month follow-up periods in the acute respiratory distress cohort and 0.96 (95% CI, 0.92-0.98), 0.93 (95% CI, 0.87-0.96), and 0.85 (95% CI, 0.74-0.91) in the pulmonary fibrosis cohort, respectively. Receiving a graft from a donor with a heavy and prolonged history of smoking was associated with worse overall survival in the acute respiratory distress syndrome cohort, whereas the characteristics associated with worse overall survival in the pulmonary fibrosis cohort included female recipient, male donor, and high recipient body mass index. Conclusions and Relevance: In this study, outcomes following lung transplant were similar in patients with irreversible respiratory failure due to COVID-19 and those with other pretransplant etiologies.

Effect of a vascular endothelial cadherin antagonist in a rat lung transplant model.

BACKGROUND: Adherens junctions are critically important in control of endothelial cell permeability. Bß15-42 is a peptide product of fibrin degradation that binds to vascular endothelial cadherin, the major component of endothelial adherens junctions. We tested the hypothesis that Bß15-42 improves lung function in our rat lung transplant model. METHODS: Bß15-42 was administered to donors before lung retrieval and to recipients by continuous intravenous infusion, or just to recipients, or neither. Recipients were monitored, anesthetized and ventilated, for 6 hours. Outcome measures were indices of lung function (edema [wet-to-dry weight ratio], oxygenation, dynamic compliance) and bronchoalveolar fluid measures of inflammation (protein, cell count, differential, and cytokines). RESULTS: Bß15-42 therapy was associated with improved graft lung function, including less edema, and improved oxygenation and airway pressure, particularly if Bß15-42 was administered to both the donor and recipient. However, Bß15-42 had little or no effect on bronchoalveolar fluid measures of inflammation. Analysis of bronchoalveolar fluid protein concentration showed Bß15-42 may enhance alveolar fluid clearance. CONCLUSIONS: Bß15-42 may be a useful therapy to reduce edema and improve graft function after lung transplant, alone or as an adjunct to other therapies.

Postmortem and ex vivo carbon monoxide ventilation reduces injury in rat lungs transplanted from non-heart-beating donors.

OBJECTIVE: We sought to determine whether ventilation of lungs after death in non-heart-beating donors with carbon monoxide during warm ischemia and ex vivo lung perfusion and after transplant would reduce ischemia-reperfusion injury and improve lung function. METHODS: One hour after death, Sprague-Dawley rats were ventilated for another hour with 60% oxygen (control group) or 500 ppm carbon monoxide in 60% oxygen (CO-vent group; n=6/group). Then, lungs were flushed with 20 mL cold Perfadex, stored cold for 1 hour, then warmed to 37 °C in an ex vivo lung perfusion circuit perfused with Steen solution. At 37 °C, lungs were ventilated for 15 minutes with alveolar gas with or without 500 ppm carbon monoxide, then perfusion-cooled to 20 °C, flushed with cold Perfadex and stored cold for 2 hours. The left lung was transplanted using a modified cuff technique. Recipients were ventilated with 60% oxygen with or without carbon monoxide. One hour after transplant, we measured blood gases from the left pulmonary vein and aorta, and wet-to-dry ratio of both lungs. The RNA and protein extracted from graft lungs underwent real-time polymerase chain reaction and Western blotting, and measurement of cyclic guanosine monophosphate by enzyme-linked immunosorbent assay. RESULTS: Carbon monoxide ventilation begun 1 hour after death reduced wet/dry ratio after ex vivo lung perfusion. After transplantation, the carbon monoxide-ventilation group had better oxygenation; higher levels of tissue cyclic guanosine monophosphate, heme oxidase-1 expression, and p38 phosphorylation; reduced c-Jun N-terminal kinase phosphorylation; and reduced expression of interleukin-6 and interleukin-1ß messenger RNA. CONCLUSIONS: Administration of carbon monoxide to the deceased donor and non-heart-beating donor lungs reduces ischemia-reperfusion injury in rat lungs transplanted from non-heart-beating donors. Therapy to the deceased donor via the airway may improve post-transplant lung function.

Simulation experience enhances medical students' interest in cardiothoracic surgery.

BACKGROUND: Applications to cardiothoracic training programs have declined dramatically. Increased effort in recruiting trainees is paramount. In this study, we test our hypothesis that mentored instruction on cardiothoracic simulators will enhance the interest of junior medical students in cardiothoracic surgery. METHODS: First- and second-year medical students were recruited from a "surgery interest group" to receive mentored instruction on high-fidelity cardiothoracic simulators. Before and after simulation assessment tools were used to assess attitudes toward simulation, general surgery, and cardiothoracic surgery. RESULTS: Forty-four medical students participated in the study. Although 80% of the students were interested in pursuing a career in surgery before the course, the majority (64%) indicated they were "neutral" about pursuing a career in cardiothoracic surgery. After participating in the course, 61% of the students agreed or strongly agreed that they were interested in pursuing a career in cardiothoracic surgery (p = 0.001). When asked to select a surgical subspecialty for their third-year clerkship rotation, 18% of the students selected thoracic surgery before participating in the simulator course versus 39% after completing the course. This increase was most evident among the female participants, of whom only 3 (12%) selected a thoracic rotation before the simulator course versus 9 (35%) after completion of the course (p < 0.05). CONCLUSIONS: High-fidelity surgical simulators are an effective way to introduce medical students to cardiothoracic surgery. Participation in moderated simulator sessions improves attitudes toward cardiothoracic surgery as a career choice and correlates with a greater interest in selecting thoracic surgery as a third-year clerkship rotation. The role of surgical simulation as a recruitment tool should be further delineated.

In vitro modeling of nonhypoxic cold ischemia-reperfusion simulating lung transplantation.

OBJECTIVE: Although anoxia/reoxygenation of cultured cells has been used to model lung ischemia-reperfusion injury, this does not accurately mimic events experienced by lung cells while a lung is retrieved from a donor, stored, and transplanted. We developed an in vitro model of nonhypoxic ischemia-reperfusion injury to simulate these events. METHODS: Human umbilical vein endothelial cells underwent simulated cold ischemia by replacing 37 degrees C culture media with 4 degrees C Perfadex (Vitrolife, Kungsbacka, Sweden) solution for 5 hours in 100% O(2). Culture dishes were allowed to warm to room temperature for 1 hour (implantation), and then Perfadex solution was replaced with 37 degrees C culture media (reperfusion). RESULTS: During cold ischemia, the human umbilical vein endothelial cell filamentous actin cytoskeleton quickly became rearranged, and gaps developed in the previously confluent monolayer occupying 20% of the surface area. Simulated reperfusion resulted in reorganization to a confluent monolayer. Development of gaps was not due to enhanced necrosis based on lactate dehydrogenase retention assay. Endothelial cytoskeletal rearrangement could account for early edema caused by ischemia-reperfusion injury with reperfusion. Mitogen-activated protein kinase and nuclear factor kappaB activation occurred with simulated reperfusion despite normoxia. Levels of the proinflammatory cytokines interleukin 6 and interleukin 8 were significantly increased in media at the end of reperfusion. CONCLUSIONS: Exposing human umbilical vein endothelial cells to simulated cold ischemia without hypoxia causes reversible cytoskeletal alterations, activation of inflammatory pathways, and elaboration of cytokines. Because this model accurately depicts events occurring during lung transplantation, it will be useful to explore mechanisms regulating lung cell response to this unique form of ischemia-reperfusion injury.

Ex-vivo perfusion and ventilation of rat lungs from non-heart-beating donors before transplant.

BACKGROUND: We developed an ex-vivo circuit to evaluate human lungs retrieved from non-heart-beating donors. We assessed the effect of a similar circuit on the function of transplanted rat lungs retrieved from non-heart-beating donors. METHODS: One hour after death, Sprague-Dawley rat heart-lung blocks were flushed with 20 mL of cold Perfadex, stored cold for 1 hour, then warmed to 37 degrees C in a circuit perfused with Earle's crystalloid solution with or without washed porcine erythrocytes (hematocrit 12% to 15%). At 37 degrees C, lungs were ventilated for 15 minutes with alveolar gas, perfusion-cooled to 20 degrees C, flushed again with cold Perfadex, and then stored cold for 2.5 hours. The left lung was transplanted using a modified cuff technique with flow probes on the main and left pulmonary arteries. After 1 hour of reperfusion, arterial blood gases from the left pulmonary vein and wet/dry weight ratio (W/D) of both donor lungs were determined. Lungs transplanted after retrieval from heart-beating or non-heart-beating donors served as controls (n = 6 per group). RESULTS: Lungs gained weight in the circuit but W/D and PO2 were similar after transplantation for all groups. After transplantation, vascular resistance was higher and dynamic compliance was lower for lungs perfused in the circuit. Myeloperoxidase and conjugated diene levels were modestly elevated in lungs transplanted from non-heart-beating donors irrespective of perfusion in the circuit. CONCLUSIONS: Rat lungs are suitable for transplant after ex-vivo perfusion and ventilation. This model closely mimics methods used to evaluate the function of lungs retrieved from human non-heart-beating donors and can economically evaluate ex-vivo therapies for lungs retrieved from non-heart-beating donors.

Inhaled nitric oxide reduces ischemia-reperfusion injury in rat lungs from non-heart-beating donors.

OBJECTIVE: If lungs could be retrieved from non-heart-beating donors, the critical shortage of lungs for transplantation could be alleviated. However, lungs subjected to warm ischemia develop edema when reperfused. We hypothesized that ventilation of rat lungs from non-heart-beating donors with nitric oxide during the period of warm ischemia alone, with reperfusion, or both might reduce ischemia-reperfusion injury. METHODS: An isolated perfused rat lung model measured the filtration coefficient and accumulation of lung water by the wet/dry weight ratio. Donor rats were euthanized, and then lungs were retrieved immediately after death or 2 or 3 hours postmortem. Lungs retrieved postmortem were either not ventilated or ventilated with 100% oxygen alone or 40 ppm nitric oxide in oxygen. In the circuit, lungs were ventilated with alveolar gas with or without 40 ppm nitric oxide. RESULTS: Nitric oxide administration to the non-heart-beating donor or in the perfusion circuit reduced filtration coefficient and wet/dry weight ratio. Lungs retrieved 2 hours postmortem ventilated with nitric oxide or treated with nitric oxide on reperfusion had filtration coefficients and wet/dry weight ratios similar to those of lungs retrieved immediately after death. Nitric oxide was most beneficial when administered both during warm ischemia and at reperfusion in lungs retrieved 3 hours postmortem. Nitric oxide administration in the circuit was associated with increased lung levels of lung cyclic guanosine monophosphate, determined by enzyme-linked immunosorbent assay. CONCLUSIONS: Administration of nitric oxide to non-heart-beating donors during warm ischemia and with reperfusion might facilitate transplantation of lungs from non-heart-beating donors by reducing ischemia-reperfusion injury and capillary leak.

Ex vivo evaluation of human lungs for transplant suitability.

BACKGROUND: If lungs could be retrieved from non-heart-beating donors, the critical shortage of lungs for transplant could be alleviated. An obstacle to this approach is the inability to predict these lungs' suitability for transplant. We used human lungs deemed unsuitable for transplant to develop a method to perfuse and ventilate human lungs ex vivo to assess gas exchange and vascular resistance, and to perform bronchoscopic inspection and radiographic evaluation. METHODS: Lungs were retrieved from six brain-dead organ donors after cold Perfadex (Vitrolife, Kungsbacka, Sweden) flush, stored cold for 6 to 13 hours (mean, 8.7 hours) then perfused and rewarmed in a modified cardiopulmonary bypass circuit. Circuit perfusate was buffered colloid-crystalloid containing type-specific leukocyte-filtered blood (hematocrit of 10%-12%), circulated through a membrane oxygenator ventilated with CO2 and nitrogen to deoxygenate it. Lungs were ventilated with fraction of inspired oxygen (Fio2) 0.5 when 32 degrees C was reached. Gas exchange and vascular resistance was assessed at 5 L/minute flow at 37 degrees C, Fio2 0.5 and 1.0. Bronchoscopy, plain radiographs, and spiral computed tomographic (CT) scans were performed. Lung biopsies were obtained pre- and post-reperfusion. RESULTS: Ex vivo perfusion did not cause increased wet to dry ratio, or major abnormalities by microscopy but was associated with elevated tissue levels of conjugated dienes. The alveolar-arterial difference in partial pressure of oxygen (Pao2)/Fio2 ratio in the ex vivo circuit was generally higher than in the six donors. Ex vivo radiographs and CT scans were abnormal in all lungs, confirming unsuitability of these lungs for transplant. CONCLUSIONS: Ex vivo evaluation of human lungs is feasible and may be useful to evaluate transplant suitability of lungs retrieved after circulatory arrest from non-heart-beating donors.

Trends in lung pH and PO2 after circulatory arrest: implications for non-heart-beating donors and cell culture models of lung ischemia-reperfusion injury.

BACKGROUND: A better understanding of lung tissue environment after circulatory arrest would allow more accurate cell culture models to study ischemia-reperfusion lung injury and facilitate retrieval of lungs from non-heart-beating donors. METHODS: To establish the time course of changes in pH and PO2 in lung tissue after circulatory arrest, 12 Sprague-Dawley rats were sacrificed. After sternotomy, pH and PO2 microelectrodes were inserted into the lungs and sealed by application of Focal Seal. Rats were maintained at normothermia (37 degrees C). Two groups of rats (n = 6 atelectatic, n = 6 room air-inflated) were followed for 4 hours after arrest, when lung tissue adenine nucleotide levels were measured by chromatography and cell death was quantified by trypan blue exclusion. Human umbilical vein endothelial cells underwent simulated ischemia and 6 hours of cold storage by replacement of culture medium with cold Perfadex. Interleukin (IL)-6 and IL-8 were measured in medium 21 hours later by enzyme-linked immunosorbent assay (ELISA). RESULTS: In both groups of rats, lung [H+] increased linearly with time. In atelectatic lungs, PO2 fell precipitously, but in inflated lungs, PO2 decreased linearly for 60 to 75 minutes post-mortem and then became stable. After 4 hours at 37 degrees C, most parenchymal lung cells were dead in both groups. IL-6 and IL-8 levels increased significantly in medium of cultured endothelial cells subjected to cold storage without hypoxia. CONCLUSIONS: In room-air-inflated lungs maintained at 37 degrees C, oxygen consumption continues for at least 1 hour after circulatory arrest. Warm atelectasis is poorly tolerated. Hypothermic storage can induce elaboration of cytokines by endothelial cells in the absence of hypoxia.

Isoproterenol reduces ischemia-reperfusion lung injury despite beta-blockade.

BACKGROUND: If lungs could be retrieved from non-heart-beating donors (NHBDs), the shortage of lungs for transplantation could be alleviated. The use of lungs from NHBDs is associated with a mandatory warm ischemic interval, which results in ischemia-reperfusion injury upon reperfusion. In an earlier study, rat lungs retrieved 2-h postmortem from NHBDs had reduced capillary leak measured by filtration coefficient (Kfc) when reperfused with isoproterenol (iso), associated with an increase in lung tissue levels of cyclic AMP (cAMP). The objective was to determine if this decrease in Kfc was because of beta-stimulation, or would persist despite beta-blockade. MATERIALS AND METHODS: Donor rats were treated intraperitoneally with beta-blockade (propranolol or pindolol) or carrier, sacrificed, and lungs were retrieved immediately or 2 h postmortem. The lungs were reperfused with or without iso and the beta-blockers in the reperfusate. Outcome measures were Kfc, wet:dry weight ratio (W/D), lung levels of adenine nucleotides and cAMP. RESULTS: Lungs retrieved immediately after death had normal Kfc and W/D. After 2 h of ischemia, Kfc and W/D were markedly elevated in controls (no drug) and lungs reperfused with beta-blockers alone. Isoproterenol-reperfusion decreased Kfc and W/D significantly (P < 0.01) even in the presence of beta-blockade. Lung cAMP levels were increased only with iso in the absence of beta-blockade. CONCLUSIONS: The attenuation of ischemia-reperfusion injury because of iso occurs even in the presence of beta-blockade, and may not be a result of beta-stimulated increased cAMP.

Assessment of real-time 3D visualization for cardiothoracic diagnostic evaluation and surgery planning.

RATIONALE AND OBJECTIVES: Three-dimensional (3D) real-time volume rendering has demonstrated improvements in clinical care for several areas of radiological imaging. We test whether advanced real-time rendering techniques combined with an effective user interface will allow radiologists and surgeons to improve their performance for cardiothoracic surgery planning and diagnostic evaluation. MATERIAL AND METHODS: An interactive combination 3D and 2D visualization system developed at the University of North Carolina at Chapel Hill was compared against standard tiled 2D slice presentation on a viewbox. The system was evaluated for 23 complex cardiothoracic computed tomographic (CT) cases including heart-lung and lung transplantation, tumor resection, airway stent placement, repair of congenital heart defects, aortic aneurysm repair, and resection of pulmonary arteriovenous malformation. Radiologists and surgeons recorded their impressions with and without the use of the interactive visualization system. RESULTS: The cardiothoracic surgeons reported positive benefits to using the 3D visualizations. The addition of the 3D visualization changed the surgical plan (65% of cases), increased the surgeon's confidence (on average 40% per case), and correlated well with the anatomy found at surgery (95% of cases). The radiologists reported fewer and less major changes than the surgeons in their understanding of the case due to the 3D visualization. They found new findings or additional information about existing findings in 66% of the cases; however, they changed their radiology report in only 14% of the cases. CONCLUSION: With the appropriate choice of 3D real-time volume rendering and a well-designed user interface, both surgeons and radiologists benefit from viewing an interactive 3D visualization in addition to 2D images for surgery planning and diagnostic evaluation of complex cardiothoracic cases. This study finds that 3D visualization is especially helpful to the surgeon in understanding the case, and in communicating and planning the surgery. These results suggest that including real-time 3D visualization would be of clinical benefit for complex cardiothoracic CT cases.

Thoracoscopy using a substernal handport for palpation.

BACKGROUND: A substernal handport allows palpation of the lung and thus circumvents one of the major limitations of thoracoscopy. METHODS: This approach has been used in 24 consecutive patients, primarily during planned metastasectomy or when palpation was needed for deeper or smaller lesions that were difficult to find. RESULTS: No long-term complications from this procedure were noted, and the 3 early complications were either minor or unrelated to the procedure. This approach allowed adequate resection to be accomplished by a less invasive approach in 67% of patients, although conversion to an open procedure was necessary in 33% of patients for anatomic and technical reasons. Among the 16 patients who underwent this procedure alone, the median length of stay in the hospital was 3 days. The rate of incomplete resection and of recurrence after metastasectomy was comparable to that for an open approach. CONCLUSIONS: Our experience documents that a substernal handport is safe, does not compromise the ability to perform an adequate metastasectomy, and allows biopsy of lesions that are otherwise not amenable to a minimally invasive approach. This technique should be included in the standard armamentarium of approaches for thoracic surgery.

Trigger for intercellular adhesion molecule-1 expression in rat lungs transplanted from non-heart-beating donors.

BACKGROUND: Lung transplantation from non-heart-beating donors causes ischemia-reperfusion injury. We sought to determine the trigger for expression of intercellular adhesion molecule-1 (ICAM-1) caused by ischemia-reperfusion injury. METHODS: Thirty-six Sprague-Dawley rats underwent left lung transplant (six groups of 6). Lungs were transplanted immediately after arrest, or from non-heart-beating donors after 2 hours of oxygen-ventilation or no ventilation. Recipients were reperfused for 4 or 6 hours, then lungs were stained with a mouse anti-rat ICAM-1 monoclonal antibody, developed with avidin-biotin peroxidase to a biotinylated anti-mouse immunoglobin G antibody. Intercellular adhesion molecule-1 expression was graded by two masked observers as 0 = absent, 1 = weak, or 2 = strong in alveoli, arterioles, and venules. Explanted recipient left lungs served as negative controls, and positive controls were generated 6 hours after intraperitoneal injection of endotoxin. Intercellular adhesion molecule-1 expression above baseline among groups was compared by Fisher's exact test. RESULTS: Constitutive expression of ICAM-1 was present in rat lung alveoli, with 24 of 35 controls staining weakly and 4 of 35 strongly positive in alveolar areas. Intercellular adhesion molecule-1 expression was not increased in transplanted lungs evaluated after 4 hours of reperfusion, even lungs retrieved from non-heart-beating donors. But when non-heart-beating donor lungs were assessed 6 hours after onset of reperfusion, ICAM-1 expression was significantly more apparent in alveolar and arteriolar areas, compared with controls and lungs transplanted immediately after arrest. CONCLUSIONS: Lungs transplanted immediately after circulatory arrest do not sustain sufficient ischemia-reperfusion injury to upregulate ICAM-1. Onset of reperfusion is the signal for ICAM-1 expression, not the onset of ischemia or the total duration of ischemic and reperfusion time together. Strategies at reperfusion may minimize ICAM-1 expression.

Pulmonary preservation studies: effects on endothelial function and pulmonary adenine nucleotides.

BACKGROUND: Lung transplantation is an effective therapy plagued by a high incidence of early graft dysfunction, in part because of reperfusion injury. The optimal preservation solution for lung transplantation is unknown. We performed experiments using an isolated perfused rat lung model to test the effect of lung preservation with three solutions commonly used in clinical practice. METHODS: Lungs were retrieved from Sprague-Dawley rats and flushed with one of three solutions: modified Euro-Collins (MEC), University of Wisconsin (UW), or low potassium dextran and glucose (LPDG), then stored cold for varying periods before reperfusion with Earle's balanced salt solution using the isolated perfused rat lung model. Outcome measures were capillary filtration coefficient (Kfc), wet-to-dry weight ratio, and lung tissue levels of adenine nucleotides and cyclic AMP. RESULTS: All lungs functioned well after 4 hr of storage. By 6 hr, UW-flushed lungs had a lower Kfc than LPDG-flushed lungs. After 8 hr of storage, only UW-flushed lungs had a measurable Kfc. Adenine nucleotide levels were higher in UW-flushed lungs after prolonged storage. Cyclic AMP levels correlated with Kfc in all groups. CONCLUSIONS: Early changes in endothelial permeability seemed to be better attenuated in lungs flushed with UW compared with LPDG or MEC; this was associated with higher amounts of adenine nucleotides. MEC-flushed lungs failed earlier than LPDG-flushed or UW-flushed lungs. The content of the solution may be more important for lung preservation than whether the ionic composition is intracellular or extracellular.