Porcine Lung Research Articles

A rapid and robust organ repair polyacrylamide/alginate adhesive hydrogel mediated via interfacial adhesion-trigger molecules

Adhesive hydrogels have been widely explored as tissue adhesives for wound sealing and repair. However, developing adhesive hydrogels with simple preparation techniques and strong adhesion to internal organs in a short time remains a challenge. In this study, we developed a strategy for robust and rapid tissue adhesion of internal organ sealing and repair by an interfacial adhesion-molecule triggered hydrogel system. In this system, polyphenol molecules act as adhesion-trigger reagents to achieve fast and strong adhesion of polyacrylamide/alginate hydrogels on the surface of wound tissue by rapidly forming abundant hydrogen bonds at the interface. The adhesion energy is significantly enhanced by 45 times under the mediation of polyphenol adhesion-trigger molecules, resulting in a robust (> 600 J m−2) tissue adhesion in just 30 s. This interfacial adhesion system demonstrates good biocompatibility, strong sealing performance on multiple organs (porcine heart, lung, stomach, and intestine), and excellent repair properties in gastric perforation wounds of rabbits in vivo. Moreover, immunocytochemical and transcriptomic analyses reveal that this interfacial adhesion system significantly promotes vascular regeneration and inhibits inflammatory responses during wound repairing. The proposed hydrogel provides a facile strategy for rapid and robust tissue adhesion, and shows potential applications in organ sealing and repair.

Comparative study of percutaneous and transbronchial lung parenchyma cryoablation using a porcine model

BACKGROUND: Cryoablation is less invasive for certain selected and inoperable pulmonary lesions, which can be treated via percutaneous or transbronchial approaches. OBJECTIVE: To examine the effect of percutaneous cryoablation using an porcine lung parenchyma model. MATERIALS AND METHODS: Nitrogen-cooled cryoprobe was inserted into the posterior lobe of the peripheral lung parenchyma of six healthy female pigs percutaneously under CT guidance. Double and triple freezethaw cycles were performed on the left lung and the right lung, respectively. CT images were obtained before, during and after cryoablation. Blood samples were collected at various time points for testing. Tissue samples from the ablation zone were obtained after cryoablation for histopathological analysis. Data from the percutaneous study were compared with previously published transbronchial cryoablation data. RESULTS: The cryoablation outcomes and inflammatory responses observed in the percutaneous group were largely consistent as compared to those previously published in the transbronchial groups. Similar trends in the histopathological transition from the center to the periphery of the ablation zone and tissue repair process was exhibited between two groups within 4 weeks. Two cases of pneumothorax occurred in the percutaneous group. CONCLUSION: Cryoablation of the peripheral lung parenchyma by both percutaneous and transbronchial methods is safe and effective. Transbronchial approach demonstrates a lower complication rate than the percutaneous method. Two approaches complement one another for minimally invasive treatment of lung cancers.

Therapeutic Use of Carbon Monoxide in Ex-Vivo Lung Perfusion in Donor With Prolonged Cold Ischemia

IntroductionCarbon monoxide (CO) has been shown to exert protective effects in multiple organs following ischemic injury, including the lung. The purpose of this study was to examine the effects of CO administration during ex vivo lung perfusion (EVLP) on lung grafts exposed to prolonged cold ischemia. MethodsTen porcine lungs were subjected to 18 h of cold ischemia followed by 6 h of EVLP. Lungs were randomized to EVLP alone (control, n = 5) or delivery of 500 ppm of CO during the 1st hour of EVLP (treatment, n = 5). Following EVLP, the left lungs were transplanted and reperfused for 4 h. ResultsAt the end of EVLP, pulmonary vascular resistance (P = 0.007) and wet to dry lung weight ratios (P = 0.027) were significantly reduced in CO treated lungs. Posttransplant, lung graft PaO2/FiO2 (P = 0.032) and compliance (P = 0.024) were significantly higher and peak airway pressure (P = 0.032) and wet to dry ratios (P = 0.003) were significantly lower in CO treated lungs. Interleukin-6 was significantly reduced in plasma during reperfusion in the CO treated group (P = 0.040). ConclusionsIn this preclinical porcine model, CO application during EVLP resulted in better graft performance and outcomes after reperfusion.

PneumaOCT: Pneumatic optical coherence tomography endoscopy for targeted distortion-free imaging in tortuous and narrow internal lumens.

The complex anatomy of internal luminal organs, like bronchioles, poses challenges for endoscopic optical coherence tomography (OCT). These challenges include limited steerability for targeted imaging and nonuniform rotation distortion (NURD) with proximal scanning. Using rotary micromotors for distal scanning could address NURD but raises concerns about electrical safety and costs. We present pneumaOCT, the first pneumatic OCT endoscope, comprising a steerable catheter with a soft pneumatic actuator and an imaging probe with a miniature pneumatic turbine. With a diameter of 2.8 mm, pneumaOCT allows for a bending angle of up to 237°, facilitating navigation through narrow turns. The pneumatic turbine enables adjustable imaging speeds from 51 to 446 revolutions per second. We demonstrate the pneumaOCT in vivo imaging of mouse esophagus and colon, as well as targeted and distortion-free imaging of peripheral bronchioles in a bronchial phantom and a porcine lung. This advancement substantially improves endoscopic OCT for navigational imaging in curved and narrow lumens.

Metabolomic studies reveal an organ-protective hibernation state in donor lungs preserved at 10 °C

ObjectivePrevious reports showed enhanced graft function in both healthy and injured porcine lungs after preservation at 10 °C. The objective of the study is to elucidate the mechanism of lung protection by 10 °C and identify potential therapeutic targets to improve organ preservation. MethodsMetabolomics data were analyzed from healthy and injured porcine lungs that underwent extended hypothermic preservation on ice and at 10 °C. Tissue sampled before and after preservation were subjected to untargeted metabolic profiling. Principal component analysis was performed to test for the separability of the paired samples. Significantly changed metabolites between the 2 time points were identified and analyzed to determine the underlying metabolic pathways. The levels of respiratory activity of lung tissue at hypothermic temperatures were confirmed using high resolution respirometry. ResultsIn both healthy and injured lungs (n = 5 per intervention), principal component analysis suggested minimal change in metabolites after ice preservation but significant change of metabolites after 10 °C preservation, which was associated with significantly improved lung function as assessed by ex vivo lung perfusion and lung transplantation. For healthy lungs, lipid energy pathway was found primarily active at 10 °C. For injured lungs, additional carbohydrate energy pathway and anti-ferroptosis pathways aiding organ repair were identified. These metabolic features are also key features involved in mammal hibernation. ConclusionsUntargeted metabolomics revealed a dynamic metabolic gradient for lungs stored at 10 °C. Elucidating the underlying mechanisms behind this pathway regulation may lead to strategies that will allow organs "hibernate" for days, potentially making organ banking a reality.

Microwave dielectric properties of normal, fibroelastotic, and malignant human lung tissue

Technological development of microwave treatment and detection techniques for lung cancer requires accurate and comprehensive knowledge of the microwave dielectric properties of human lung tissue. We characterize the dielectric properties of room temperature human lung tissue from 0.5 to 10 GHz for three lung tissue groups: normal, fibroelastotic, and malignant. We fit a two-pole Debye model to the measured frequency-dependent complex permittivity and calculate the median Debye parameters for the three groups. We find that malignant lung tissue is approximately 10% higher in relative permittivity and conductivity compared to normal lung tissue; this trend matches previously reported normal versus malignant data for other biological tissues. There is little contrast between benign lung tissue with fibroelastosis and malignant lung tissue. We extrapolate our data from room temperature to 37 °C using a temperature-dependence model for animal lung tissue and use the Maxwell-Garnett dielectric mixing model to predict the dielectric properties of inflation-dynamic human lung tissue; both approximations correspond with previously reported dielectric data of bovine and porcine lung tissue.

Guidelines for power and time variables for microwave ablation in porcine lung in vitro.

Determination of the appropriate ablative parameters is the key to the success and safety of microwave ablation (MWA) of lung tumors. The purpose of this study was to provide guidelines and recommendations for the optimal time and power for lung tumor MWA. MWA using a 2450-MHz system was evaluated in a porcine lung. The independent variables were power (30, 40, 50, 60, 70, and 80 W) and time (2, 4, 6, 8, 10, and 12 min), and the outcome variable was the volume of ablation. Lung tissues were procured after MWA for measurement and histological evaluation. Analysis of variance was used for statistical analysis, followed by least significant difference (LSD) t-tests where appropriate. A P value of <0.05 was considered statistically significant. The outcome variable (ablative volume) was significantly affected by time, power, and time/power interaction (P < 0.05). When the total output energy was kept constant, the combination of higher power and shorter time obtained a larger ablative volume, especially in the low- and medium-energy groups (P < 0.01). We propose guidelines for ablative volume based on different time and power variables to provide a reference for clinical applications.

Feasibility and Pathologic Outcomes of Peripheral Lung Vascular Targeted Photodynamic Therapy in a Normal Porcine Lung Model

Feasibility and Pathologic Outcomes of Peripheral Lung Vascular Targeted Photodynamic Therapy in a Normal Porcine Lung Model

Bronchoscopy-Guided High-Power Microwave Ablation in an in vivo Porcine Lung Model.

Percutaneous microwave ablation (MWA) is clinically accepted for the treatment of lung tumors and oligometastatic disease. Bronchoscopic MWA is under development and evaluation in the clinical setting. We previously reported on the development of a bronchoscopy-guided MWA system integrated with clinical virtual bronchoscopy and navigation and demonstrated the feasibility of transbronchial MWA, using a maximum power of 60 W at the catheter input. Here, we assessed the performance of bronchoscopy-guided MWA with an improved catheter (maximum power handling of up to 120 W) in normal porcine lung in vivo (as in the previous study). A total of 8 bronchoscopy-guided MWA were performed (n = 2 pigs; 4 ablations per pig) with power levels of 90 W and 120 W applied for 5 and 10 min, respectively. Virtual bronchoscopy planning and navigation guided transbronchial or endobronchial positioning of the MWA applicator for ablation of lung parenchyma. Following completion of ablations and post-procedure CT imaging, the lungs were harvested and sectioned for gross and histopathologic ablation analysis. Bronchoscopy-guided MWA with applied energy levels of 90 W/5 min and 120 W/10 min yielded ablation zones with short-axis diameters in the range of 20-28 mm (56-116% increase) as compared to ∼13 mm from our previous study (60 W/10 min). Histology of higher-power and previous lower-power ablations was consistent, including a central necrotic zone, a thermal fixation zone with intact tissue architecture, and a hemorrhagic periphery. Catheter positioning and its confirmation via intra-procedural 3D imaging (e.g., cone-beam CT) proved to be critical for ablation consistency. Bronchoscopy-guided MWA with an improved catheter designed for maximum power 120 W yields large ablations in normal porcine lung in vivo.

Near‐Infrared Afterglow Luminescence Amplification via Albumin Complexation of Semiconducting Polymer Nanoparticles for Surgical Navigation in Ex Vivo Porcine Models

AbstractAfterglow imaging, leveraging persistent luminescence following light cessation, has emerged as a promising modality for surgical interventions. However, the scarcity of efficient near‐infrared (NIR) responsive afterglow materials, along with their inherently low brightness and lack of cyclic modulation in afterglow emission, has impeded their widespread adoption. Addressing these challenges requires a strategic repurposing of afterglow materials that improve on such limitations. Here, an afterglow probe, composed of bovine serum albumin (BSA) coated with an afterglow material, a semiconducting polymer dye (SP1), called BSA@SP1 demonstrating a substantial amplification of the afterglow luminescence (≈3‐fold) compared to polymer‐lipid coated PFODBT (DSPE‐PEG@SP1) under same experimental conditions is developed. This enhancement is believed to be attributed to the electron‐rich matrix provided by BSA that immobilizes SP1 and enhances the generation of 1O2 radicals, which improves the afterglow luminescence brightness. Through molecular docking, physicochemical characterization, and optical assessments, BSA@SP1's superior afterglow properties, cyclic afterglow behavior, long‐term colloidal stability, and biocompatibility are highlighted. Furthermore, superior tissue permeation profiling of afterglow signals of BSA@SP1's compared to fluorescence signals using ex vivo tumor‐mimicking phantoms and various porcine tissue types (skin, muscle, and fat) is demonstrated. Expanding on this, to showcase BSA@SP1's potential in image‐guided surgeries, tumor‐mimicking phantoms within porcine lungs and conducted direct comparisons between fluorescence and afterglow‐guided interventions to illustrate the latter's superiority is implanted. Overall, the study introduces a promising strategy for enhancing current afterglow materials through protein complexation, resulting in both ultrahigh signal‐to‐background ratios and cyclic afterglow signals.

Restoring discarded porcine lungs by ex vivo removal of neutrophil extracellular traps

BackgroundBy causing inflammation and tissue damage, neutrophil extracellular traps (NETs) constitute an underlying mechanism of aspiration-induced lung injury, a major factor of the low utilization of donor lungs in lung transplantation (LTx). MethodTo determine whether NET removal during ex vivo lung perfusion (EVLP) can restore lung function and morphology in aspiration-damaged lungs, gastric aspiration lung injury was induced in 12 pigs. After confirmation of acute respiratory distress syndrome, the lungs were explanted and assigned to NET removal connected to EVLP (treated) (n=6) or EVLP only (non-treated) (n=6). Hemodynamic measurements were taken, and blood and tissue samples were collected to assess lung function, morphology, levels of cell-free DNA, extracellular histones, and nucleosomes as markers of NETs as well as cytokine levels. ResultsAfter EVLP and NET removal in porcine lungs, PaO2/FiO2 ratios increased significantly compared to those undergoing EVLP alone (p=0.0411). Treated lungs had lower cell-free DNA (p=0.0260) and lower levels of extracellular histones in EVLP perfusate than non-treated lungs (p=0.0260). According to histopathology, treated lungs showed less immune cell infiltration and less oedema compared with non-treated lungs which was reflected in decreased levels of pro-inflammatory cytokines in EVLP perfusate and BALF. ConclusionTo conclude, removing NETs during EVLP improved lung function and morphology in aspiration-damaged donor lungs. The ability to remove NETs during EVLP could represent a new therapeutic approach for LTx and potentially expand the donor pool for transplantation.

Normothermic Perfusion is Superior to Cold Perfusion in Porcine Ex Situ Lung Perfusion

BackgroundCold ex situ lung perfusion (ESLP) has demonstrated improved preservation in small animal ESLP compared to normothermic ESLP and cold static preservation. We hypothesized that cold negative pressure ventilation (NPV)-ESLP would improve graft function in a porcine transplantation model. MethodsFour perfusate temperatures were examined with 12 hours NPV-ESLP in a large animal transplantation model. Pig lungs were allotted to four groups: (1) Normothermia (38°C, n = 6); (2) profound hypothermia (10°C, n = 6); (3) moderate hypothermia (20°C, n = 3); (4) subnormothermia (32°C, n = 3). A fifth group subnormothermic low-flow (SNLF) perfusion was examined to assess the effect of reduced cardiac output with cold perfusion (32°C, 10% cardiac output, n = 6). ResultsOnly Normothermic and SNLF groups demonstrated acceptable oxygenation after 12 hours NPV-ESLP and were transplanted. All other groups failed prematurely. After 12 hours of ESLP, Normothermic lungs demonstrated significantly greater dynamic compliance compared to SNLF lungs (P = .03). Edema formation post-ESLP was significantly worse in the SNLF group (P = .01). There was no significant difference in pulmonary artery pressures after ESLP (P = .10); however, pulmonary vascular resistance was significantly greater in the SNLF (P = .04). Isolated left lung oxygenation 4-hours post-transplant and left lung edema formation was not significantly different between Normothermic and SNLF post-transplant (P = .09). Proinflammatory cytokines were significantly greater during SNLF-ESLP (tumor necrosis factor alpha, P < .05). ConclusionsProlonged normothermic (38°C) NPV-ESLP is superior to 10, 20, and 32°C perfusion. Normothermic ESLP of porcine lungs results in superior graft function and reduced inflammation versus SNLF-ESLP.

Porcine lungs perfused with three different flows using the 8-h open-atrium cellular ex vivo lung perfusion technique.

The number of lung transplantations is limited due to the shortage of donor lungs fulfilling the standard criteria. The ex vivo lung perfusion (EVLP) technique provides the ability of re-evaluating and potentially improving and treating marginal donor lungs. Accordingly, the technique has emerged as an essential tool to increase the much-needed donor lung pool. One of the major EVLP protocols, the Lund protocol, characterized by high pulmonary artery flow (100% of cardiac output [CO]), an open atrium, and a cellular perfusate, has demonstrated encouraging short-EVLP duration results. However, the potential of the longer EVLP duration of the protocol is yet to be investigated, a duration which is considered necessary to rescue more marginal donor lungs in future. This study aimed to achieve stable 8-h EVLP using an open-atrium cellular model with three different pulmonary artery flows in addition to determining the most optimal flow in terms of best lung performance, including lung electrolytes and least lung edema formation, perfusate and tissue inflammation, and histopathological changes, using the porcine model. EVLP was performed using a flow of either 40% (n = 6), 80% (n = 6), or 100% (n = 6) of CO. No flow rate demonstrated stable 8-h EVLP. Stable 2-h EVLP was observed in all three groups. Insignificant deterioration was observed in dynamic compliance, peak airway pressure, and oxygenation between the groups. Pulmonary vascular resistance increased significantly in the 40% group (p < .05). Electrolytes demonstrated an insignificant worsening trend with longer EVLP. Interleukin-8 (IL-8) in perfusate and tissue, wet-to-dry weight ratio, and histopathological changes after EVLP were insignificantly time dependent between the groups. This study demonstrated that stable 8-h EVLP was not feasible in an open-atrium cellular model regardless of the flow of 40%, 80%, or 100% of CO. No flow was superior in terms of lung performance, lung electrolytes changes, least lung edema formation, minimal IL-8 expression in perfusate and tissue, and histopathological changes.

Exposure to O3 and NO2 on the interfacial chemistry of the pulmonary surfactant and the mechanism of lung oxidative damage

Exposure to ozone (O3) and nitrogen dioxide (NO2) are related to pulmonary dysfunctions and various lung diseases, but the underlying biochemical mechanisms remain uncertain. Herein, the effect of inhalable oxidizing gas pollutants on the pulmonary surfactant (PS, extracted from porcine lungs), a mixture of active lipids and proteins that plays an important role in maintaining normal respiratory mechanics, is investigated in terms of the interfacial chemistry using in-vitro experiments; and the oxidative stress induced by oxidizing gases in the simulated lung fluid (SLF) supplemented with the PS is explored. The results showed that O3 and NO2 individually increased the surface tension of the PS and reduced its foaming ability; this was accompanied by the surface pressure-area isotherms of the PS monolayers shifting toward lower molecular areas, with O3 exhibiting more severe effects than NO2. Moreover, both O3 and NO2 produced reactive oxygen species (ROS) resulting in lipid peroxidation and protein damage to the PS. The formation of superoxide radicals (O2•–) was correlated with the decomposition of O3 and the reactions of O3 and NO2 with antioxidants in the SLF. These radicals, in the presence of antioxidants, led to the formation of hydrogen peroxide and hydroxyl radicals (•OH). Additionally, the direct oxidation of unsaturated lipids by O3 and NO2 further caused an increase in the ROS content. This change in the ROS chemistry and increased •OH production tentatively explain how inhalable oxidizing gases lead to oxidative stress and adverse health effects. In summary, our results indicated that inhaled O3 and NO2 exposure can significantly alter the interfacial properties of the PS, oxidize its active ingredients, and induce ROS formation in the SLF. The results of this study provide a basis for the elucidation of the potential hazards of inhaled oxidizing gas pollutants in the human respiratory system.

Characterizing the accuracy of robotic bronchoscopy in localization & targeting of small pulmonary lesions.

Considering the recent implementation of lung cancer screening guidelines, it is crucial that small pulmonary nodules are accurately diagnosed. There is a significant need for quick, precise, and minimally invasive biopsy methods, especially for patients with small lung lesions in the outer periphery. Robotic bronchoscopy (RB) has recently emerged as a novel solution. The purpose of this study was to evaluate the accuracy of RB compared to the existing standard, electromagnetic navigational bronchoscopy (EM-NB). A prospective, single-blinded, and randomized-controlled study was performed to compare the accuracy of RB to EM-NB in localizing and targeting pulmonary lesions in a porcine lung model. Four operators were tasked with navigating to four pulmonary targets in the outer periphery of a porcine lung, to which they were blinded, using both the RB and EM-NB systems. The dependent variable was accuracy. Accuracy was measured as a rate of success in lesion localization and targeting, the distance from the center of the pulmonary target, and by anatomic location. The independent variable was the navigation system, RB was compared to EM-NB using 1:1 randomization. Of 75 attempts, 72 were successful in lesion localization and 60 were successful in lesion targeting. The success rate for lesion localization was 100% with RB and 91% with EM- NB. The success rate for lesion targeting was 93% with RB and 80% for EM-NB. RB demonstrated superior accuracy in reaching the distance from the center of the lesion, at 0.62mm compared to EM-NB at 1.28mm (p = 0.001). Accuracy was improved using RB compared to EM- NB for lesions in the LLL (p = 0.025), LUL (p < 0.001), and RUL (p < 0.001). Our findings support RB as a more accurate method of navigating and localizing small peripheral pulmonary targets when compared to standard EM-NB in a porcine lung model. This may be attributed to the ability of RB to reduce substantial tissue displacement seen with standard EM-NB navigation. As the development and application of RB advances, so will the ability to accurately diagnose small peripheral lung cancer nodules, providing patients with early-stage lung cancer the best possible outcomes.

New insight on porcine carboxylesterases expression and activity in lung tissues

Over the course of the last twenty years, there has been a growing recognition of the pig's potential as a valuable model for studying human drug metabolism. This study aimed to investigate the expression, enzymatic activity, inhibitory susceptibility, and cellular localization of carboxylesterases (CES) in porcine lung tissue not yet explored. Our results showed that CESs hydrolysis activity followed Michaelis-Menten kinetics in both cytosolic and microsomal fractions of porcine lung tissues (N = 8), with comparable hydrolysis rates for tested substrates, namely 4-nitrophenyl acetate (pNPA), 4-methylumbelliferyl acetate (4-MUA), and fluorescein diacetate (FD). We also determined the CESs hydrolysis activity in a representative sample of the porcine liver that, as expected, displayed higher activity than the lung ones. The study demonstrated variable levels of enzyme activities and interindividual variability in both porcine lung fractions. Inhibition studies used to assess the CESs' involvement in the hydrolysis of pNPA, 4-MUA, and FD suggested that CESs may be the enzymes primarily involved in the metabolism of ester compounds in the pig lung tissue. Overall, this study provides insight into the distribution and diversity of CES isoforms involved in substrate hydrolysis across different cellular fractions (cytosol and microsomes) in porcine lungs.

Porcine lung tissue slices: a culture model for PRCV infection and innate immune response investigations

Respiratory coronaviruses (RCoVs) significantly threaten human health, necessitating the development of an ex vivo respiratory culture system for investigating RCoVs infection. Here, we successfully generated a porcine precision-cut lung slices (PCLSs) culture system, containing all resident lung cell types in their natural arrangement. Next, this culture system was inoculated with a porcine respiratory coronavirus (PRCV), exhibiting clinical features akin to humans who were infected by SARS-CoV-2. The results demonstrated that PRCV efficiently infected and replicated within PCLSs, targeting ciliated cells in the bronchioles, terminal bronchioles, respiratory bronchioles, and pulmonary alveoli. Additionally, through RNA-Seq analysis of the innate immune response in PCLSs following PRCV infection, expression levels of interferons, inflammatory cytokines and IFN stimulated genes were significantly upregulated. This ex vivo model may not only offer new insights into PRCV infection in the porcine respiratory tract but also serve as a valuable tool for studying human respiratory CoVs infection.

BipoJet Scissors as an Alternative to Laser in Lung Wedge Resection.

An important goal in every lung resection is airtight closure of the resected lung surface. This can be achieved with several techniques, including clamp resection, stapler, laser, and various high-frequency methods.By quantitatively measuring the air fistulaacross the resection surface of porcine lungs, two resection techniques were compared in our study: BipoJet dissecting scissors (Aesculap, Inc., Tuttlingen,Germany) and laser (Ceralas HPD®, Biolitec Inc., Jena, Germany). Following a stencil, wedge resections were performed in porcine lungs using water-irrigated bipolar scissors and laser (1350nm, 40watts, non-contact mode). The volumeof the air fistula was then measured. The irrigation technique involved the attachment of an irrigation channel to a pair of standard surgical scissors. Asodium chloride (NaCl) solution was fed at a defined flow rate, along the blades of the scissors onto the parenchyma. This technique was used on a total of 10 specimens each. Somewhat better pneumostasis was achieved with laser resection, though the difference was small and not statistically significant. The flow rate was 124mL/min/cm² after laser resection and 145 mL/min/cm² after using the BipoJet scissors. The difference was not statistically significant.Water irrigation during resection with the BipoJet scissors prevents the temperature in the tissue from exceeding 100°Cthus avoiding tissue carbonization. These scissors offer the following advantages: ease of use, no need to change instruments, no need for staff training, no protective measures, all-in-one incision/coagulation/dissection, low cost, and a clear surgical field due to the irrigation effect. Resection of lung parenchyma, e.g., during resection of metastases, is easier with BipoJet scissors and comparable to laser resection. This was established both experimentally and by resecting lung metastases.

Maximum resistance pressure at the time of lung tissue rupture after porcine lung transection using automatic linear staplers with different reinforcement methods.

Polyglycolic acid (PGA) sheets, fibrin glue, and staple line reinforcement are frequently used to prevent air leakage during lung resection. However, the optimal staple-line reinforcement method remains unclear. Cranial lung lobes of pigs were used to evaluate different staple line reinforcement methods (n = 6). Ventilator-assisted manometry was used to measure the maximum resistance pressure at the time of rupture of the lung tissue after stapling. The mean maximum resistance pressures at the time of lung tissue rupture after using the stapler alone, stapler with PGA sheet and fibrin glue, and stapler with reinforcement were 38.0 cmH2O, 51.3 cmH2O, and 62.7 cmH2O, respectively. A significant increase in the maximum resistance pressure was observed with stapler reinforcement (P < 0.001), while the differences between the other groups were not statistically significant (P = 0.055, P = 0.111). A histological assessment revealed disruption of alveolar structures near the needle-stitching site in the stapler alone, and in the stapler with PGA sheet and fibrin glue groups. Pleural rupture near the staple line was observed in the stapler with reinforcement group. The maximum resistance pressure before air leakage was significantly higher when using a stapler with reinforcement than when using a stapler alone.

Transient receptor potential vanilloid 4 channel inhibition attenuates lung ischemia-reperfusion injury in a porcine lung transplant model

ObjectiveTransient receptor potential vanilloid 4 (TRPV4) is a nonselective cation channel important in many physiological and pathophysiological processes, including pulmonary disease. Using a murine model, we previously demonstrated that TRPV4 mediates lung ischemia-reperfusion injury, the major cause of primary graft dysfunction after transplant. The current study tests the hypothesis that treatment with a TRPV4 inhibitor will attenuate lung ischemia-reperfusion injury in a clinically relevant porcine lung transplant model. MethodsA porcine left-lung transplant model was used. Animals were randomized to 2 treatment groups (n = 5/group): vehicle or GSK2193874 (selective TRPV4 inhibitor). Donor lungs underwent 30 minutes of warm ischemia and 24 hours of cold preservation before left lung allotransplantation and 4 hours of reperfusion. Vehicle or GSK2193874 (1 mg/kg) was administered to the recipient as a systemic infusion after recipient lung explant. Lung function, injury, and inflammatory biomarkers were compared. ResultsAfter transplant, left lung oxygenation was significantly improved in the TRPV4 inhibitor group after 3 and 4 hours of reperfusion. Lung histology scores and edema were significantly improved, and neutrophil infiltration was significantly reduced in the TRPV4 inhibitor group. TRPV4 inhibitor-treated recipients had significantly reduced expression of interleukin-8, high mobility group box 1, P-selectin, and tight junction proteins (occludin, claudin-5, and zonula occludens-1) in bronchoalveolar lavage fluid as well as reduced angiopoietin-2 in plasma, all indicative of preservation of endothelial barrier function. ConclusionsTreatment of lung transplant recipients with TRPV4 inhibitor significantly improves lung function and attenuates ischemia-reperfusion injury. Thus, selective TRPV4 inhibition may be a promising therapeutic strategy to prevent primary graft dysfunction after transplant.