Science.gov

Sample records for potential lung perfusion

  1. Ex vivo lung perfusion.

    PubMed

    Reeb, Jeremie; Cypel, Marcelo

    2016-03-01

    Lung transplantation is an established life-saving therapy for patients with end-stage lung disease. Unfortunately, greater success in lung transplantation is hindered by a shortage of lung donors and the relatively poor early-, mid-, and long-term outcomes associated with severe primary graft dysfunction. Ex vivo lung perfusion has emerged as a modern preservation technique that allows for a more accurate lung assessment and improvement in lung quality. This review outlines the: (i) rationale behind the method; (ii) techniques and protocols; (iii) Toronto ex vivo lung perfusion method; (iv) devices available; and (v) clinical experience worldwide. We also highlight the potential of ex vivo lung perfusion in leading a new era of lung preservation.

  2. The evolving potential for pediatric ex vivo lung perfusion.

    PubMed

    Luc, Jessica G Y; Nagendran, Jayan

    2016-02-01

    Despite the rise in the number of adult lung transplantations performed, rates of pediatric lung transplantation remain low. Lung transplantation is an accepted therapy for pediatric end-stage lung disease; however, it is limited by a shortage of donor organs. EVLP has emerged as a platform for assessment and preservation of donor lung function. EVLP has been adopted in adult lung transplantation and has successfully led to increased adult lung transplantations and donor lung utilization. We discuss the future implications of EVLP utilization, specifically, its potential evolving role in overcoming donor shortages in smaller children and adolescents to improve the quality and outcomes of lung transplantation in pediatric patients.

  3. Ex vivo lung perfusion

    PubMed Central

    Machuca, Tiago N.

    2014-01-01

    Lung transplantation (LTx) is an established treatment option for eligible patients with end-stage lung disease. Nevertheless, the imbalance between suitable donor lungs available and the increasing number of patients considered for LTx reflects in considerable waitlist mortality. Among potential alternatives to address this issue, ex vivo lung perfusion (EVLP) has emerged as a modern preservation technique that allows for more accurate lung assessment and also improvement of lung function. Its application in high-risk donor lungs has been successful and resulted in safe expansion of the donor pool. This article will: (I) review the technical details of EVLP; (II) the rationale behind the method; (III) report the worldwide clinical experience with the EVLP, including the Toronto technique and others; (IV) finally, discuss the growing literature on EVLP application for donation after cardiac death (DCD) lungs. PMID:25132972

  4. Contemporary review of the organ care system in lung transplantation: potential advantages of a portable ex-vivo lung perfusion system.

    PubMed

    Schmack, Bastian; Weymann, Alexander; Mohite, Prashant; Garcia Saez, Diana; Zych, Bartlomiej; Sabashnikov, Anton; Zeriouh, Mohamed; Schamroth, Joel; Koch, Achim; Soresi, Simona; Ananiadou, Olga; De Robertis, Fabio; Karck, Matthias; Simon, Andre Ruediger; Popov, Aron Frederik

    2016-11-01

    Lung transplantation remains the definite treatment for various end-stage lung diseases. Cold flush perfusion, the standard method for organ procurement has severe limitations. Organ Care System (OCS; TransMedics, Inc., Andover, USA) is an approved method to preserve hearts for transplantation that allows for greatly reduced cold ischemic time. Consequently, the use of an adapted OCS lung as a portable full ex-vivo lung perfusion system in lung transplantation is currently under close evaluation. Areas covered: The aim of this article is to review the advantages and the role of the OCS in the field of lung transplantation by reviewing the latest literature and evaluating this novel procurement technique in the context of conventional methods like cold flush and regular ex-vivo lung perfusion. Expert commentary: The use of OCS in the field of lung transplantation has great potential for improved patients outcomes and is justified in cases with (i) marginal donor lungs, (ii) foreseeable long time of transportation (iii) high-risk recipient or donor /recipient profiles, particularly in the setting of an overall increasing need for suitable donor organs. Results from two major multi-centre prospective studies are pending to objectively assess the possible advantages of this portable ex-vivo lung perfusion system.

  5. (68) Ga-Ca-phytate particles: A potential lung perfusion agent of synthetic origin prepared in a cold kit format.

    PubMed

    Hsieh, William; Ali, Masood; Praehofer, Renee; Tsopelas, Chris

    2016-10-01

    The objective of this study was to investigate the radiosynthesis of (68) Ga-Ca-phytate particles and then characterize the formulation for radiochemical purity, radioactive particle size distribution, and biodistribution in normal rats. This radiotracer was prepared using a commercial phytate cold kit after reconstitution with saline, (68) Ga-chloride generator eluent, calcium chloride, and air, then heating at 100°C for 30 minutes to achieve 99% radiochemical purity of (68) Ga-particles that were 21% 3-5 μm, 8% 5-15 μm, and 71% >15 μm in diameter. This optimal formulation was stable for 2 hours at room temperature. Intravenous administration of (68) Ga-particles in rats resulted in an uptake of 93% in the lungs, 4% in the liver plus spleen, and 3% in the carcass after 20 minutes. Two-thirds of the carcass activity was radioactive blood, likely to be (68) Ga-transferrin. The positron emission tomography image was superior than the (99m) Tc-MAA image because it displayed high lung uptake against a low background. Low uptake by the liver, spleen did not interfere with the diagnostic quality, and faint activity in the submandibular (salivary) glands was due to (68) Ga-transferrin. The preclinical data so far indicate that (68) Ga-Ca-phytate particles have good potential as a lung perfusion imaging agent. Copyright © 2016 John Wiley & Sons, Ltd.

  6. Ex Vivo Lung Perfusion: Establishment and Operationalization in Iran.

    PubMed

    Shafaghi, Shadi; Abbasi Dezfuli, Azizollah; Ansari Aval, Zahra; Sheikhy, Kambiz; Farzanegan, Behrooz; Mortaz, Esmaeil; Emami, Habib; Aigner, Clemens; Hosseini-Baharanchi, Fatemeh Sadat; Najafizadeh, Katayoun

    2017-02-01

    Although the number of lung transplants is limited because of general shortage of organ donors, ex vivo lung perfusion is a novel method with 2 main benefits, including better evaluation of lung potential and recovery of injured lungs. The main aim of this study was to establish and operationalize ex vivo lung perfusion as the first experience in Iran. This was a prospective operational research study on 5 cases, including 1 pig from Vienna Medical University and 4 patients from Masih Daneshvari Hospital. All organ donations from brain dead donors were evaluated according to lung transplant or ex vivo lung perfusion criteria from May 2013 to July 2015 in Tehran, Iran. If a donor did not have any sign of severe chest trauma or pneumonia but had poor oxygenation due to possible atelectasis or neurogenic pulmonary edema, their lungs were included for ex vivo lung perfusion. A successful trend in the difference between the pulmonary arterial Po2 and the left atrial Po2 was observed, as well as an increasing pattern in other functional parameters, including dynamic lung compliance and a decreasing trend in pulmonary vascular resistance. These initial trials indicate that ex vivo lung perfusion can lead to remarkable progress in lung transplant in Iran. They also provide several important pieces of guidance for successful ex vivo lung perfusion, including the necessity of following standard lung retrieval procedures and monitoring temperature and pressure precisely. The development of novel methods can provide opportunities for further research studies on lungs of deceased donors and lead to undiscovered findings. By keeping this science up to date in Iran and developing such new and creative methods, we can reveal effective strategies to promote the quality of donor lungs to support patients on transplant wait lists.

  7. Ventilation/perfusion lung scintigraphy. Multiple applications besides pulmonary embolism.

    PubMed

    Sinzinger, Helmut; Rodrigues, Margarida; Kummer, Friedrich

    2013-01-01

    Ventilation/perfusion scintigraphy is the diagnostic tool of choice for detection and monitoring of pulmonary embolism. However, the knowledge on its value for other or concurrent pathologies is poor. In this review scintigraphic characteristics of the main pathologies, interpretation and artefacts are described. Together with the understanding of pathophysiology of the lung, the potential gain of information derived from ventilation/perfusion scintigraphy is much higher than generally believed. In conclusion, ventilation/perfusion scintigraphy not only in PE but also in other lung diseases is underused, its value and clinical potential underestimated.

  8. Transplantation of initially rejected donor lungs after ex vivo lung perfusion.

    PubMed

    Wallinder, Andreas; Ricksten, Sven-Erik; Hansson, Christoffer; Riise, Gerdt C; Silverborn, Martin; Liden, Hans; Olausson, Michael; Dellgren, Göran

    2012-11-01

    Ex vivo lung perfusion has the potential to increase the number of patients treated with lung transplantation. Our initial clinical experience with ex vivo lung perfusion is reviewed as well as early clinical outcome in patients transplanted with reconditioned lungs. Six pairs of donor lungs deemed unsuitable for transplantation underwent ex vivo lung perfusion with Steen solution mixed with red blood cells to a hematocrit of 10% to 15%. After reconditioning, lung function was evaluated and acceptable lungs were transplanted. Technical experience with ex vivo lung perfusion as well as clinical outcome for patients transplanted with ex vivo lung perfusion-treated lungs were evaluated. Donor lungs initially rejected either as a result of an inferior partial pressure of arterial oxygen/ fraction of inspired oxygen (n = 5; mean, 20.5 kPa; range, 9.1-29.9 kPa) or infiltrate on chest radiograph (n = 1) improved their oxygenation capacity to a mean partial pressure of arterial oxygen/fraction of inspired oxygen of 57 ± 10 kPa during the ex vivo lung perfusion (mean improvement, 33.6 kPa; range, 21-51 kPa; P < .01). During evaluation, hemodynamic (flow, vascular resistance, pressure) and respiratory (peak airway pressure, compliance) parameters were stable. Two single lungs were not used for lung transplantation because of subpleural hematoma or edema. Six recipients from the regular waiting list underwent single (n = 2) or double (n = 4) lung transplantation. One patient had primary graft dysfunction grade 2 at 72 hours. Median time to extubation was 7 hours. All patients survived 30 days and were discharged in good condition from the hospital. The use of ex vivo lung perfusion seems safe and indicates that some lungs otherwise refused for lung transplantation can be recovered and transplanted with acceptable short-term results. Copyright © 2012 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

  9. Distributions of perfusion and lung water.

    PubMed

    Ekeh, S U; Chu, R Y; Ficken, V J; Allen, E W; Ryals, C J

    1990-01-01

    We investigated the feasibility of using 123I-iodoantipyrine (123I-IAP) and 99mTc-labeled macroaggregated albumin (99mTc-MAA) to describe and compare the distributions of perfusion and water content in lung injuries. These radiopharmaceuticals were administered to 9 rabbits, 5 control and 4 with lung injuries. Isolated lungs were imaged by a scintillation gamma camera. The distribution of 123I-IAP outlined the entire lung mass whereas perfusion defect in the distribution of 99mTc-MAA was seen clearly in the case of severe lung injury.

  10. The low specificity of postoperative perfusion lung scan defects.

    PubMed Central

    Walker, I; Aukland, P; Hirsh, J; Coates, G; Cockshott, P; Taylor, R; Hull, R

    1981-01-01

    Ventilation and perfusion lung scans were performed preoperatively and postoperatively in 169 patients and classified blindly according to preset criteria. Perfusion lung scan abnormalities were present in 25 (15%) of the preoperative scans and 42 (25%) of the postoperative scans; 16 (38%) of the 42 abnormal postoperative scans were identical to the preoperative scans. Perfusion defects indicating a "high probability" of pulmonary embolism (lobar or segmental defects) were present in 5 preoperative scans and 10 postoperative scans; the 10 postoperative scans were classified as showing "definite" (5), "possible" (1) or "no" (4) pulmonary embolism on the basis of the preoperative scan and the ventilation scan; none of the 10 patients had clinical evidence of pulmonary embolism. Venous thrombosis was present in 12 patients, including 4 of the patients whose lung scans showed definite pulmonary embolism. Thus, postoperative perfusion lung scan defects are potentially misleading even when large. PMID:7459778

  11. The effect of ex vivo lung perfusion on microbial load in human donor lungs.

    PubMed

    Andreasson, Anders; Karamanou, Danai M; Perry, John D; Perry, Audrey; Ӧzalp, Faruk; Butt, Tanveer; Morley, Katie E; Walden, Hannah R; Clark, Stephen C; Prabhu, Mahesh; Corris, Paul A; Gould, Kate; Fisher, Andrew J; Dark, John H

    2014-09-01

    Ex vivo lung perfusion (EVLP) has emerged as a technique to potentially recondition unusable donor lungs for transplantation. Beneficial effects of EVLP on physiologic function have been reported, but little is known about the effect of normothermic perfusion on the infectious burden of the donor lung. In this study, we investigated the effect of EVLP on the microbial load of human donor lungs. Lungs from 18 human donors considered unusable for transplantation underwent EVLP with a perfusate containing high-dose, empirical, broad-spectrum anti-microbial agents. Quantitative cultures of bacteria and fungi were performed on bronchoalveolar lavage fluid from the donor lung before and after 3 to 6 hours of perfusion. The identification of any organisms and changes in number of colony forming units before and after EVLP were assessed and anti-microbial susceptibilities identified. Thirteen out of 18 lungs had positive cultures, with bacterial loads significantly decreasing after EVLP. Yeast loads increased when no anti-fungal treatment was given, but were reduced when prophylactic anti-fungal treatment was added to the circuit. Six lungs were ultimately transplanted into patients, all of whom survived to hospital discharge. There was 1 death at 11 months. Our study shows that EVLP with high-dose, empirical anti-microbial agents in the perfusate is associated with an effective reduction in the microbial burden of the donor lung, a benefit that has not previously been demonstrated. Copyright © 2014 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

  12. Lung Perfusion Scanning in Hepatic Cirrhosis

    PubMed Central

    Stanley, N. N.; Ackrill, P.; Wood, J.

    1972-01-01

    Abnormal lung perfusion scans using radioactive particles were found in five out of six cases of hepatic cirrhosis with arterial hypoxaemia. None had clinical evidence of cardiopulmonary disease or signs of pulmonary embolism on arteriography. The scan defects are probably caused by a disorder of the pulmonary microvasculature, which may show regional variation in severity. ImagesFIG. 1FIG. 2 PMID:4645896

  13. Lung Ventilation/Perfusion Scan

    MedlinePlus

    ... Scan Lung VQ Scan Related Topics Arrhythmia Cough Deep Vein Thrombosis Pulmonary Embolism Send a link to NHLBI to someone by ... this topic. Related reading Chest X Ray Cough Deep Vein Thrombosis Pulmonary Embolism Rate This Content: Updated: December 9, 2016 Twitter ...

  14. Lung perfusion studies after transcatheter closure of persistent ductus arteriosus with the Amplatzer duct occluder.

    PubMed

    Polat, Tugcin Bora; Celebi, Ahmet; Hacımahmutoglu, Sevim; Akdeniz, Celal; Erdem, Abdullah; Fırat, Fatih

    2010-09-01

    Reduced left lung perfusion has been described after transcatheter closure of the patent ductus arteriosus (PDA) with several prostheses. Although the Amplatzer ductal occluder (ADO) device is currently the most widely used occluder for closure of large-sized PDAs, the potential consequences of flow distribution to the lungs of this device have not been completely clarified. We evaluated lung perfusion following occlusion of PDA with the ADO device. Forty-seven patients underwent successful transcatheter PDA occlusion using the ADO device were included in this study. Lung perfusion scans were performed 6 months after the procedure. Decreased perfusion to the left lung (defined as < 40% of total lung flow) was observed in 17 patients (36%), 5 of whom were low-weight symptomatic infants. Ductal ampulla length was significantly shorter and minimal ductal diameter to ampulla diameter ratio was significantly higher in patients with decreased left lung perfusion and correlated well with left lung perfusion values (r = 0.516 and r = -0.501, respectively). A cut-off value of ≤ 5.8 mm for the ductal ampulla length and ≥ 1.9 for ampulla diameter to ampulla length ratio showed high sensitivity and specificity for reduced lung perfusion. The incidence of abnormal left lung perfusion is high 6 months after transcatheter closure of PDA with the ADO, more likely in the low weight symptomatic infants and in patients with a short duct or a relatively shallow duct having abrupt narrowing of a large ampulla.

  15. Cytokine expression profile in human lungs undergoing normothermic ex-vivo lung perfusion.

    PubMed

    Sadaria, Miral R; Smith, Phillip D; Fullerton, David A; Justison, George A; Lee, Joon H; Puskas, Ferenc; Grover, Frederick L; Cleveland, Joseph C; Reece, T Brett; Weyant, Michael J

    2011-08-01

    A donor lung shortage prevents patients from receiving life-saving transplants. Ex-vivo lung perfusion (EVLP) is a viable means of expanding the donor pool by evaluating and potentially improving donor lung function. The metabolic and inflammatory effects of EVLP on human lung tissue are currently unknown. We sought to establish representative cytokine expression in human donor lungs meeting acceptable lung transplant criteria after prolonged normothermic EVLP. Seven single human lungs not meeting traditional transplantation criteria for various reasons underwent normothermic EVLP. Lungs were perfused with deoxygenated colloid, rewarmed, and ventilated per standard protocol. Lung function was evaluated every hour. Biopsies were taken at 1, 6, and 12 hours. Inflammatory cytokines were quantitatively measured using a human cytokine magnetic bead-based multiplex assay. All lungs met traditional transplant criteria after EVLP. The partial pressure of arterial oxygen and physiologic lung function significantly improved (p<0.05). No pulmonary edema was formed, and histology demonstrated no evidence of acute lung injury. Interleukin (IL)-6, IL-8, granulocyte colony-stimulating factor, and monocyte chemotactic protein-1 were upregulated, while granulocyte macrophage colony-stimulating factor was downregulated during EVLP (p<0.05). IL-1β, IL-4, IL-7, IL-12, interferon-γ, macrophage inflammatory protein-1β, and tumor necrosis factor-α were detectable and unchanged. Ex-vivo lung perfusion demonstrates the ability to improve oxygenation and physiologic lung function in donor lungs unacceptable for transplantation without injury to the lung. We establish here a cytokine expression profile in human lungs undergoing normothermic EVLP. These data can be used in the future to explore novel targeted therapies for ischemia-reperfusion injury. Copyright © 2011 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  16. Initial experience of dual-energy lung perfusion CT using a dual-source CT system in children.

    PubMed

    Goo, Hyun Woo

    2010-09-01

    Initial experience of dual-source dual-energy (DE) lung perfusion CT in children is described. In addition to traditional identification of pulmonary emboli, the assessment of lung perfusion is technically feasible with dual-source DE CT in children with acceptable radiation dose. This article describes how to perform dual-source DE lung perfusion CT in children, including the optimization of intravenous injection method and CT dose parameters. How to produce weighted-average CT images for the assessment of pulmonary emboli and colour-coded perfusion maps for the assessment of regional lung perfusion is also detailed. Lung perfusion status can then be evaluated on perfusion maps by means of either qualitative or quantitative analysis. Potential advantages and disadvantages of this emerging CT technique compared to lung perfusion scintigraphy and cardiac MRI are discussed.

  17. Ex vivo lung perfusion allows successful transplantation of donor lungs from hanging victims.

    PubMed

    Bennett, Daine T; Reece, T Brett; Smith, Phillip D; Grandhi, Miral Sadaria; Rove, Jessica A Yu; Justison, George A; Mitchell, John D; Fullerton, David A; Zamora, Martin R; Weyant, Michael J

    2014-09-01

    Donor lungs acquired from victims of asphyxiation by hanging are not routinely used for lung transplantation because of the associated lung injury. Ex vivo lung perfusion (EVLP) is a technique to evaluate marginal donor lungs before transplantation. We report here our experience with the use of EVLP in donor lungs procured from victims of asphyxia by hanging. Lungs from 5 donors who became brain dead secondary to hanging were evaluated by EVLP. Donor organs were perfused according to trial protocol. Donor lungs were accepted for transplantation if they maintained a PaO2 greater than or equal to 350 mm Hg, had a clear roentgenogram, and had no significant worsening of physiologic metrics. Perfused organs included single and double lung blocs, and all were perfused without technical incident. Three of the 5 donor organs evaluated met criteria for transplantation after 3 hours of EVLP and were transplanted. Donor organs rejected for transplantation showed either signs of worsening PaO2 or deterioration of physiologic metrics. There were no intraoperative complications in the patients who underwent transplantation, and all were alive at 30 days. We report here the successful use of EVLP to assess donor lungs acquired from victims of asphyxiation by hanging. The use of EVLP in this particular group of donors has the potential to expand the available donor pool. We demonstrate that EVLP is a viable option for evaluating the function of lung allografts before transplantation and would recommend that all donor lungs obtained from hanging victims undergo EVLP to assess their suitability for transplantation. Copyright © 2014 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  18. Lung transplantation from donors after circulatory death using portable ex vivo lung perfusion

    PubMed Central

    Bozso, Sabin; Vasanthan, Vishnu; Luc, Jessica GY; Kinaschuk, Katie; Freed, Darren; Nagendran, Jayan

    2015-01-01

    BACKGROUND: Donation after circulatory death is a novel method of increasing the number of donor lungs available for transplantation. Using organs from donors after circulatory death has the potential to increase the number of transplants performed. METHODS: Three bilateral lung transplants from donors after circulatory death were performed over a six-month period. Following organ retrieval, all sets of lungs were placed on a portable ex vivo lung perfusion device for evaluation and preservation. RESULTS: Lung function remained stable during portable ex vivo perfusion, with improvement in partial pressure of oxygen/fraction of inspired oxygen ratios. Mechanical ventilation was discontinued within 48 h for each recipient and no patient stayed in the intensive care unit longer than eight days. There was no postgraft dysfunction at 72 h in two of the three recipients. Ninety-day mortality for all recipients was 0% and all maintain excellent forced expiratory volume in 1 s and forced vital capacity values post-transplantation. CONCLUSION: The authors report excellent results with their initial experience using donors after circulatory death after portable ex vivo lung perfusion. It is hoped this will allow for the most efficient use of available donor lungs, leading to more transplants and fewer deaths for potential recipients on wait lists. PMID:25379654

  19. Perfusion lung scanning: differentiation of primary from thromboembolic pulmonary hypertension

    SciTech Connect

    Lisbona, R.; Kreisman, H.; Novales-Diaz, J.; Derbekyan, V.

    1985-01-01

    Of eight patients with pulmonary arterial hypertension, final diagnosis established by autopsy or angiography, four had primary hypertension and four hypertension from thromboembolism. The perfusion lung scan was distinctly different in the two groups. The lung scan in primary pulmonary hypertension was associated with nonsegmental, patchy defects of perfusion, while in thromboembolic hypertensives it was characterized by segmental and/or lobar defects of perfusion with or without subsegmental defects. The perfusion lung scan is a valuable, noninvasive study in the evaluation of the patient with pulmonary hypertension of undetermined cause and in the exclusion of occult large-vessel pulmonary thromboembolism.

  20. Ex Vivo Lung Perfusion: A Key Tool for Translational Science in the Lungs.

    PubMed

    Tane, Shinya; Noda, Kentaro; Shigemura, Norihisa

    2017-02-23

    Ex vivo lung perfusion (EVLP) promises to be a comprehensive platform for assessment, re-conditioning, and preservation for donor lungs and has been dramatically changing the face of clinical lung transplantation. Besides its increasing role in lung transplantation, EVLP has also been recognized as a useful tool for translational research involving the lungs. Based on recent remarkable evidence and experience using EVLP in lung transplantation, there is growing interest in and expectations for the use of EVLP beyond the field of lung transplantation. By combining EVLP with advances in regenerative medicine, stem cell biology, and oncology, the evolving technology of EVLP has a tremendous potential to advance pulmonary medicine and science. In this review, we revisit recent advances in EVLP technology and research and discuss the future translation of EVLP applications into life-changing medicine.

  1. Scintigraphic perfusion patterns in patients with diffuse lung disease

    SciTech Connect

    Newman, G.E.; Sullivan, D.C.; Gottschalk, A.; Putman, C.E.

    1982-04-01

    Perfusion scintigrams of 55 patients with radiographic evidence of diffuse lung disease were reviewed. Thirty-nine had acute and/or chronic changes caused by congestive heart failure, and 16 had diffuse reticulonodular disease. A normal or near-normal perfusion pattern was seen in 40/55 (73%), and this finding was equally common in the two groups. The authors conclude that perfusion scintigraphy is useful in excluding pulmonary embolism in patients with radiographic evidence of diffuse, symmetrical lung disease.

  2. Automated quantitative analysis of ventilation-perfusion lung scintigrams

    SciTech Connect

    Burton, G.H.; Vernon, P.; Seed, W.A.

    1984-05-01

    An automated computer analysis of ventilation (Kr-81m) and perfusion (Tc-99m) lung images has been devised that produces a graphical image of the distribution of ventilation and perfusion, and of ventilation-perfusion ratios. The analysis has overcome the following problems: the identification of the midline between two lungs and the lung boundaries, the exclusion of extrapulmonary radioactivity, the superimposition of lung images of different sizes, and the format for presentation of the data. Therefore, lung images of different sizes and shapes may be compared with each other. The analysis has been used to develop normal ranges from 55 volunteers. Comparison of younger and older age groups of men and women show small but significant differences in the distribution of ventilation and perfusion, but no differences in ventilation-perfusion ratios.

  3. Reversible ventilation and perfusion abnormalities in unilateral obstructed lung

    SciTech Connect

    Ward, H.E.; Jones, R.L.; King, E.G.; Sproule, B.J.; Fortune, R.L.

    1982-01-01

    An intraluminal carcinoid tumor obstructing the left mainstem bronchus produced hypoxemia through alteration in ventilation/perfusion matching. Studies of regional lung function using 133-xenon (/sup 133/Xe) and a multiprobe computerized instrumentation system documented a reduction of perfusion to 22 percent and ventilation to 6 percent of the total. There was negligible washout of intravenously injected /sup 133/Xe from the left lung consistent with air trapping. Four days after left mainstem bronchial sleeve resection, perfusion, ventilation and washout of injected xenon had significantly improved and by four months postresection, all measurements were virtually normal, although complete restoration of perfusion in relation to ventilation was delayed. Regional lung function studied with a multiprobe system in this patient provided a clinical model for the study of ventilation and perfusion inter-relationships in large airway obstruction and demonstrated that a prolonged time may be required for return of perfusion to normal.

  4. The stripe sign: correlation of radionuclide ventilation and perfusion with He-3 magnetic resonance lung imaging

    PubMed

    Teates; Brookeman; Daniel; Truwit; Parekh; Mugler; de Lange EE

    1999-10-01

    PURPOSE: The aim of this study was to correlate regional ventilation and perfusion images and perfusion SPECT with images made using a newly developed magnetic resonance ventilation (MRV) method. MATERIALS AND METHODS: The investigation included a single patient with chronic obstructive pulmonary disease and a healthy control participant. Ventilation and perfusion images using Xe-133 and Tc-99m MAA, including perfusion SPECT, were compared with single-breath MRV with hyperpolarized He-3. RESULTS: Ventilation and perfusion defects correspond to areas of poor ventilation on MRV. High-resolution MRV images show preservation of bronchi and acinus units in areas of the "stripe sign" on the V/Q study. CONCLUSIONS: MRV imaging confirms that the stripe sign seen on nuclear perfusion imaging correlates with subsegmental preserved lung. MRV imaging has the potential for high-resolution innovative studies of subsegmental lung function, using either He-3 or Xe-129 hyperpolarized gases.

  5. Perfusion Scintigraphy and Patient Selection for Lung Volume Reduction Surgery

    PubMed Central

    Chandra, Divay; Lipson, David A.; Hoffman, Eric A.; Hansen-Flaschen, John; Sciurba, Frank C.; DeCamp, Malcolm M.; Reilly, John J.; Washko, George R.

    2010-01-01

    Rationale: It is unclear if lung perfusion can predict response to lung volume reduction surgery (LVRS). Objectives: To study the role of perfusion scintigraphy in patient selection for LVRS. Methods: We performed an intention-to-treat analysis of 1,045 of 1,218 patients enrolled in the National Emphysema Treatment Trial who were non–high risk for LVRS and had complete perfusion scintigraphy results at baseline. The median follow-up was 6.0 years. Patients were classified as having upper or non–upper lobe–predominant emphysema on visual examination of the chest computed tomography and high or low exercise capacity on cardiopulmonary exercise testing at baseline. Low upper zone perfusion was defined as less than 20% of total lung perfusion distributed to the upper third of both lungs as measured on perfusion scintigraphy. Measurements and Main Results: Among 284 of 1,045 patients with upper lobe–predominant emphysema and low exercise capacity at baseline, the 202 with low upper zone perfusion had lower mortality with LVRS versus medical management (risk ratio [RR], 0.56; P = 0.008) unlike the remaining 82 with high perfusion where mortality was unchanged (RR, 0.97; P = 0.62). Similarly, among 404 of 1,045 patients with upper lobe–predominant emphysema and high exercise capacity, the 278 with low upper zone perfusion had lower mortality with LVRS (RR, 0.70; P = 0.02) unlike the remaining 126 with high perfusion (RR, 1.05; P = 1.00). Among the 357 patients with non–upper lobe–predominant emphysema (75 with low and 282 with high exercise capacity) there was no improvement in survival with LVRS and measurement of upper zone perfusion did not contribute new prognostic information. Conclusions: Compared with optimal medical management, LVRS reduces mortality in patients with upper lobe–predominant emphysema when there is low rather than high perfusion to the upper lung. PMID:20538961

  6. Perfusion scintigraphy and patient selection for lung volume reduction surgery.

    PubMed

    Chandra, Divay; Lipson, David A; Hoffman, Eric A; Hansen-Flaschen, John; Sciurba, Frank C; Decamp, Malcolm M; Reilly, John J; Washko, George R

    2010-10-01

    It is unclear if lung perfusion can predict response to lung volume reduction surgery (LVRS). To study the role of perfusion scintigraphy in patient selection for LVRS. We performed an intention-to-treat analysis of 1,045 of 1,218 patients enrolled in the National Emphysema Treatment Trial who were non-high risk for LVRS and had complete perfusion scintigraphy results at baseline. The median follow-up was 6.0 years. Patients were classified as having upper or non-upper lobe-predominant emphysema on visual examination of the chest computed tomography and high or low exercise capacity on cardiopulmonary exercise testing at baseline. Low upper zone perfusion was defined as less than 20% of total lung perfusion distributed to the upper third of both lungs as measured on perfusion scintigraphy. Among 284 of 1,045 patients with upper lobe-predominant emphysema and low exercise capacity at baseline, the 202 with low upper zone perfusion had lower mortality with LVRS versus medical management (risk ratio [RR], 0.56; P = 0.008) unlike the remaining 82 with high perfusion where mortality was unchanged (RR, 0.97; P = 0.62). Similarly, among 404 of 1,045 patients with upper lobe-predominant emphysema and high exercise capacity, the 278 with low upper zone perfusion had lower mortality with LVRS (RR, 0.70; P = 0.02) unlike the remaining 126 with high perfusion (RR, 1.05; P = 1.00). Among the 357 patients with non-upper lobe-predominant emphysema (75 with low and 282 with high exercise capacity) there was no improvement in survival with LVRS and measurement of upper zone perfusion did not contribute new prognostic information. Compared with optimal medical management, LVRS reduces mortality in patients with upper lobe-predominant emphysema when there is low rather than high perfusion to the upper lung.

  7. Magnetic Resonance Imaging of Ventilation and Perfusion in the Lung

    NASA Technical Reports Server (NTRS)

    Prisk, Gordon Kim (Inventor); Hopkins, Susan Roberta (Inventor); Buxton, Richard Bruce (Inventor); Pereira De Sa, Rui Carlos (Inventor); Theilmann, Rebecca Jean (Inventor); Cronin, Matthew Vincent (Inventor)

    2017-01-01

    Methods, devices, and systems are disclosed for implementing a fully quantitative non-injectable contrast proton MRI technique to measure spatial ventilation-perfusion (VA/Q) matching and spatial distribution of ventilation and perfusion. In one aspect, a method using MRI to characterize ventilation and perfusion in a lung includes acquiring an MR image of the lung having MR data in a voxel and obtaining a breathing frequency parameter, determining a water density value, a specific ventilation value, and a perfusion value in at least one voxel of the MR image based on the MR data and using the water density value to determine an air content value, and determining a ventilation-perfusion ratio value that is the product of the specific ventilation value, the air content value, the inverse of the perfusion value, and the breathing frequency.

  8. Serial perfusion in native lungs in patients with idiopathic pulmonary fibrosis and other interstitial lung diseases after single lung transplantation.

    PubMed

    Sokai, Akihiko; Handa, Tomohiro; Chen, Fengshi; Tanizawa, Kiminobu; Aoyama, Akihiro; Kubo, Takeshi; Ikezoe, Kohei; Nakatsuka, Yoshinari; Oguma, Tsuyoshi; Hirai, Toyohiro; Nagai, Sonoko; Chin, Kazuo; Date, Hiroshi; Mishima, Michiaki

    2016-04-01

    Lung perfusions after single lung transplantation (SLT) have not been fully clarified in patients with interstitial lung disease (ILD). The present study aimed to investigate temporal changes in native lung perfusion and their associated clinical factors in patients with ILD who have undergone SLT. Eleven patients were enrolled. Perfusion scintigraphy was serially performed up to 12 months after SLT. Correlations between the post-operative perfusion ratio in the native lung and clinical parameters, including pre-operative perfusion ratio and computed tomography (CT) volumetric parameters, were evaluated. On average, the perfusion ratio of the native lung was maintained at approximately 30% until 12 months after SLT. However, the ratio declined more significantly in idiopathic pulmonary fibrosis (IPF) than in other ILDs (p = 0.014). The perfusion ratio before SLT was significantly correlated with that at three months after SLT (ρ = 0.64, p = 0.048). The temporal change of the perfusion ratio in the native lung did not correlate with those of the CT parameters. The pre-operative perfusion ratio may predict the post-operative perfusion ratio of the native lung shortly after SLT in ILD. Perfusion of the native lung may decline faster in IPF compared with other ILDs. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. Assessment of lung tumor response by perfusion CT.

    PubMed

    Coche, E

    2013-01-01

    Perfusion CT permits evaluation of lung cancer angiogenesis and response to therapy by demonstrating alterations in lung tumor vascularity. It is advocated that perfusion CT performed shortly after initiating therapy may provide a better evaluation of physiological changes rather than the conventional size assessment obtained with RECIST. The radiation dose,the volume of contrast medium delivered to the patient and the reproducibility of blood flow parameters remain an issue for this type of investigation.

  10. Surface Fluorescence Studies of Tissue Mitochondrial Redox State in Isolated Perfused Rat Lungs

    PubMed Central

    Staniszewski, Kevin; Audi, Said H.; Sepehr, Reyhaneh; Jacobs, Elizabeth R.; Ranji, Mahsa

    2012-01-01

    We designed a fiber-optic-based optoelectronic fluorometer to measure emitted fluorescence from the auto-fluorescent electron carriers NADH and FAD of the mitochondrial electron transport chain (ETC). The ratio of NADH to FAD is called the redox ratio (RR = NADH/FAD) and is an indicator of the oxidoreductive state of tissue. We evaluated the fluorometer by measuring the fluorescence intensities of NADH and FAD at the surface of isolated, perfused rat lungs. Alterations of lung mitochondrial metabolic state were achieved by the addition of rotenone (complex I inhibitor), potassium cyanide (KCN, complex IV inhibitor) and/or pentachlorophenol (PCP, uncoupler) into the perfusate recirculating through the lung. Rotenone- or KCN-containing perfusate increased RR by 21% and 30%, respectively. In contrast, PCP-containing perfusate decreased RR by 27%. These changes are consistent with the established effects of rotenone, KCN, and PCP on the redox status of the ETC. Addition of blood to perfusate quenched NADH and FAD signal, but had no effect of RR. This study demonstrates the capacity of fluorometry to detect a change in mitochondrial redox state in isolated perfused lungs, and suggests the potential of fluorometry for use in in vivo experiments to extract a sensitive measure of lung tissue’s health in real-time. PMID:23238793

  11. Ex Vivo Perfusion Treatment of Infection in Human Donor Lungs.

    PubMed

    Nakajima, D; Cypel, M; Bonato, R; Machuca, T N; Iskender, I; Hashimoto, K; Linacre, V; Chen, M; Coutinho, R; Azad, S; Martinu, T; Waddell, T K; Hwang, D M; Husain, S; Liu, M; Keshavjee, S

    2016-04-01

    Ex vivo lung perfusion (EVLP) is a platform to treat infected donor lungs with antibiotic therapy before lung transplantation. Human donor lungs that were rejected for transplantation because of clinical concern regarding infection were randomly assigned to two groups. In the antibiotic group (n = 8), lungs underwent EVLP for 12 h with high-dose antibiotics (ciprofloxacin 400 mg or azithromycin 500 mg, vancomycin 15 mg/kg, and meropenem 2 g). In the control group (n = 7), lungs underwent EVLP for 12 h without antibiotics. A quantitative decrease in bacterial counts in bronchoalveolar lavage (BAL) was found in all antibiotic-treated cases but in only two control cases. Perfusate endotoxin levels at 12 h were significantly lower in the antibiotic group compared with the control group. EVLP with broad-spectrum antibiotic therapy significantly improved pulmonary oxygenation and compliance and reduced pulmonary vascular resistance. Perfusate endotoxin levels at 12 h were strongly correlated with levels of perfusates tumor necrosis factor α, IL-1β and macrophage inflammatory proteins 1α and 1β at 12 h. In conclusion, EVLP treatment of infected donor lungs with broad-spectrum antibiotics significantly reduced BAL bacterial counts and endotoxin levels and improved donor lung function. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

  12. Ex vivo lung perfusion: a comprehensive review of the development and exploration of future trends.

    PubMed

    Roman, Marius A; Nair, Sukumaran; Tsui, Steven; Dunning, John; Parmar, Jasvir S

    2013-09-01

    There is a critical mismatch between the number of donor lungs available and the demand for lungs for transplantation. This has created unacceptably high waiting-list mortality for lung transplant recipients. Currently (2012) in the United Kingdom, there are 216 patients on the lung transplant waiting list and 17 on heart and lung transplant list. The waiting times for suitable lungs average 412 days, with an increasing mortality and morbidity among the patients on the lung transplant list. Ex vivo lung perfusion (EVLP) has emerged as a technique for the assessment, resuscitation, and potential repair of suboptimal donor lungs. This is a rapidly developing field with significant clinical implications. In this review article, we critically appraise the background developments that have led to our current clinical practice. In particular, we focus on the human and animal experience, the different perfusion-ventilation strategies, and the impact of different perfusates and leukocyte filters. Finally, we examine EVLP as a potential research tool. This will provide insight into EVLP and its future development in the field of clinical lung transplantation.

  13. Comparison of lung preservation solutions in human lungs using an ex vivo lung perfusion experimental model.

    PubMed

    Medeiros, Israel L; Pêgo-Fernandes, Paulo M; Mariani, Alessandro W; Fernandes, Flávio G; Unterpertinger, Fernando V; Canzian, Mauro; Jatene, Fabio B

    2012-09-01

    Experimental studies on lung preservation have always been performed using animal models. We present ex vivo lung perfusion as a new model for the study of lung preservation. Using human lungs instead of animal models may bring the results of experimental studies closer to what could be expected in clinical practice. Brain-dead donors whose lungs had been declined by transplantation teams were used. The cases were randomized into two groups. In Group 1, Perfadex®was used for pulmonary preservation, and in Group 2, LPDnac, a solution manufactured in Brazil, was used. An ex vivo lung perfusion system was used, and the lungs were ventilated and perfused after 10 hours of cold ischemia. The extent of ischemic-reperfusion injury was measured using functional and histological parameters. After reperfusion, the mean oxygenation capacity was 405.3 mmHg in Group 1 and 406.0 mmHg in Group 2 (p = 0.98). The mean pulmonary vascular resistance values were 697.6 and 378.3 dyn·s·cm-5, respectively (p =0.035). The mean pulmonary compliance was 46.8 cm H20 in Group 1 and 49.3 ml/cm H20 in Group 2 (p =0.816). The mean wet/dry weight ratios were 2.06 and 2.02, respectively (p=0.87). The mean Lung Injury Scores for the biopsy performed after reperfusion were 4.37 and 4.37 in Groups 1 and 2, respectively (p = 1.0), and the apoptotic cell counts were 118.75/mm² and 137.50/mm², respectively (p=0.71). The locally produced preservation solution proved to be as good as Perfadex®. The clinical use of LPDnac may reduce costs in our centers. Therefore, it is important to develop new models to study lung preservation.

  14. Argon and xenon ventilation during prolonged ex vivo lung perfusion.

    PubMed

    Martens, An; Montoli, Matteo; Faggi, Giulio; Katz, Ira; Pype, Jan; Vanaudenaerde, Bart M; Van Raemdonck, Dirk E M; Neyrinck, Arne P

    2016-03-01

    Evidence supports the use of ex vivo lung perfusion (EVLP) as a platform for active reconditioning before transplantation to increase the potential donor pool and to reduce the incidence of primary graft dysfunction. A promising reconditioning strategy is the administration of inhaled noble gases based on their organoprotective effects. Our aim was to validate a porcine warm ischemic lung injury model and investigate postconditioning with argon (Ar) or xenon (Xe) during prolonged EVLP. Domestic pigs were divided in four groups (n = 5 per group). In the negative control group, lungs were flushed immediately. In the positive control (PC) and treatment (Ar, Xe) groups, lungs were flushed after a warm ischemic interval of 2-h in situ. All grafts were evaluated and treated during normothermic EVLP for 6 h. In the control groups, lungs were ventilated with 70% N2/30% O2 and in the treatment groups with 70% Ar/30% O2 or 70% Xe/30% O2, respectively. Outcome parameters were physiological variables (pulmonary vascular resistance, peak airway pressures, and PaO2/FiO2), histology, wet-to-dry weight ratio, bronchoalveolar lavage, and computed tomography scan. A significant difference between negative control and PC for pulmonary vascular resistance, peak airway pressures, PaO2/FiO2, wet-to-dry weight ratio, histology, and computed tomography-imaging was observed. No significant differences between the injury group (PC) and the treatment groups (Ar, Xe) were found. We validated a reproducible prolonged 6-h EVLP model with 2 h of warm ischemia and described the physiological changes over time. In this model, ventilation during EVLP with Ar or Xe administered postinjury did not improve graft function. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Propofol attenuates oxidant-induced acute lung injury in an isolated perfused rabbit-lung model.

    PubMed

    Yumoto, Masato; Nishida, Osamu; Nakamura, Fujio; Katsuya, Hirotada

    2005-01-01

    Reactive oxygen species have been strongly implicated in the pathogenesis of acute lung injury (ALI). Some animal studies suggest that free radical scavengers inhibit the onset of oxidant-induced ALI. Propofol (2,6-diisopropylphenol) is chemically similar to phenol-based free radical scavengers such as the endogenous antioxidant vitamin E. Both in vivo and in vitro studies have suggested that propofol has antioxidant potential. We hypothesized that propofol may attenuate ALI by acting as a free-radical scavenger. We investigated the effects of propofol on oxidant-induced ALI induced by purine and xanthine oxidase (XO), in isolated perfused rabbit lung, in two series of experiments. In series 1, we examined the relationship between the severity of ALI and the presence of hydrogen peroxide (H2O2). In series 2, we evaluated the effects of propofol on attenuating ALI and the dose dependence of these effects. The lungs were perfused for 90 min, and we evaluated the effects on the severity of ALI by monitoring the pulmonary capillary filtration coefficient (Kfc), pulmonary arterial pressure (Ppa), and the pulmonary capillary hydrostatic pressure (Ppc). In series 1, treatment with catalase (an H2O2 scavenger) prior to the addition of purine and XO resulted in complete prevention of ALI, suggesting that H2O2 may be involved closely in the pathogenesis of ALI. In series 2, pretreatment with propofol at concentrations in excess of 0.5 mM significantly inhibited the increases in the Kfc values, and that in excess of 0.75 mM significantly inhibited the increase in the Ppa values. Propofol attenuates oxidant-induced ALI in an isolated perfused rabbit lung model, probably due to its antioxidant action.

  16. Evaluation of pulmonary perfusion in lung regions showing isolated xenon-133 ventilation washout defects

    SciTech Connect

    Bushnell, D.L.; Sood, K.B.; Shirazi, P.; Pal, I. )

    1990-08-01

    Xenon-133 washout phase imaging is often used to help determine whether the etiology of a perfusion defect is embolic or due to pulmonary parenchymal pathology, such as chronic obstructive pulmonary disease. This study was designed to evaluate the pulmonary blood flow patterns associated with isolated defects on xenon washout images. Scintigraphic lung studies were reviewed until 100 cases with abnormal ventilation results were obtained. Ventilation abnormalities were compared with the corresponding perfusion scan results at the same anatomic site. Of the 208 individual lung regions with xenon abnormalities, 111 showed isolated washout defects (that is, with normal washin). Ninety-four of these 111 sites showed either normal perfusion or a small, nonsegmental corresponding perfusion defect. Three segmental perfusion defects were noted in association with isolated xenon retention. In each of these cases, however, the patient was felt actually to have pulmonary embolism. Thus, it is recommended that, for interpretation of scintigraphic images in the assessment of pulmonary embolism, lung pathology associated with isolated xenon retention not be considered a potential cause for large or segmental perfusion defects.

  17. A novel dual ex vivo lung perfusion technique improves immediate outcomes in an experimental model of lung transplantation.

    PubMed

    Tanaka, Y; Noda, K; Isse, K; Tobita, K; Maniwa, Y; Bhama, J K; D'Cunha, J; Bermudez, C A; Luketich, J D; Shigemura, N

    2015-05-01

    The lungs are dually perfused by the pulmonary artery and the bronchial arteries. This study aimed to test the feasibility of dual-perfusion techniques with the bronchial artery circulation and pulmonary artery circulation synchronously perfused using ex vivo lung perfusion (EVLP) and evaluate the effects of dual-perfusion on posttransplant lung graft function. Using rat heart-lung blocks, we developed a dual-perfusion EVLP circuit (dual-EVLP), and compared cellular metabolism, expression of inflammatory mediators, and posttransplant graft function in lung allografts maintained with dual-EVLP, standard-EVLP, or cold static preservation. The microvasculature in lung grafts after transplant was objectively evaluated using microcomputed tomography angiography. Lung grafts subjected to dual-EVLP exhibited significantly better lung graft function with reduced proinflammatory profiles and more mitochondrial biogenesis, leading to better posttransplant function and compliance, as compared with standard-EVLP or static cold preservation. Interestingly, lung grafts maintained on dual-EVLP exhibited remarkably increased microvasculature and perfusion as compared with lungs maintained on standard-EVLP. Our results suggest that lung grafts can be perfused and preserved using dual-perfusion EVLP techniques that contribute to better graft function by reducing proinflammatory profiles and activating mitochondrial respiration. Dual-EVLP also yields better posttransplant graft function through increased microvasculature and better perfusion of the lung grafts after transplantation. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

  18. Ventilation and perfusion magnetic resonance imaging of the lung

    PubMed Central

    Bauman, Grzegorz; Eichinger, Monika

    2012-01-01

    Summary A close interaction between the respiratory pump, pulmonary parenchyma and blood circulation is essential for a normal lung function. Many pulmonary diseases present, especially in their initial phase, a variable regional impairment of ventilation and perfusion. In the last decades various techniques have been established to measure the lung function. Besides the global pulmonary function tests (PFTs) imaging techniques gained increasing importance to detect local variations in lung function, especially for ventilation and perfusion assessment. Imaging modalities allow for a deeper regional insight into pathophysiological processes and enable improved planning of invasive procedures. In contrast to computed tomography (CT) and the nuclear medicine techniques, magnetic resonance imaging (MRI), as a radiation free imaging modality gained increasing importance since the early 1990 for the assessment of pulmonary function. The major inherent problems of lung tissue, namely the low proton density and the pulmonary and cardiac motion, were overcome in the last years by a constant progress in MR technology. Some MR techniques are still under development, a process which is driven by scientific questions regarding the physiology and pathophysiology of pulmonary diseases, as well as by the need for fast and robust clinically applicable imaging techniques as safe therapy monitoring tools. MRI can be considered a promising ionizing-free alternative to techniques like CT or nuclear medicine techniques for the evaluation of lung function. The goal of this article is to provide an overview on selected MRI techniques for the assessment of pulmonary ventilation and perfusion. PMID:22802864

  19. Protective effect of plasmin in marginal donor lungs in an ex vivo lung perfusion model.

    PubMed

    Motoyama, Hideki; Chen, Fengshi; Ohsumi, Akihiro; Hijiya, Kyoko; Okita, Kenji; Nakajima, Daisuke; Sakamoto, Jin; Yamada, Tetsu; Sato, Masaaki; Aoyama, Akihiro; Bando, Toru; Date, Hiroshi

    2013-05-01

    Donor lung thrombi are considered an important etiology for primary graft dysfunction in lung transplantation. We hypothesized that thrombolysis before lung transplantation could alleviate ischemia-reperfusion injury. This study was designed to evaluate the effect of the fibrinolytic agent plasmin on lungs damaged by thrombi in an ex vivo lung perfusion (EVLP) system. Rats were divided into control, non-plasmin, and plasmin groups (n = 7 each). In the control and plasmin groups, cardiac arrest was induced by withdrawal of mechanical ventilation without heparinization. Ventilation was restarted 150 minutes after cardiac arrest. The lungs were flushed, and the heart and lungs were excised en bloc. The lungs were perfused in the EVLP system for 60 minutes, and plasmin or placebo was administered upon EVLP initiation. Fibrin/fibrinogen degradation products in the perfusate were significantly higher in the plasmin group than in the control and non-control groups (p < 0.001 for both). Plasmin administration significantly decreased pulmonary vascular resistance (plasmin vs non-plasmin, p = 0.011) and inhibited the exacerbation of dynamic compliance (plasmin vs non-plasmin, p = 0.003). Lung weight gain was less in the plasmin group than in the non-plasmin group (p = 0.04). Our results confirmed that plasmin administration in an EVLP model dissolved thrombi in the lungs, resulting in reconditioning of the lungs as assessed by various physiologic parameters. Copyright © 2013 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

  20. Regional pulmonary perfusion following human heart-lung transplantation

    SciTech Connect

    Lisbona, R.; Hakim, T.S.; Dean, G.W.; Langleben, D.; Guerraty, A.; Levy, R.D. )

    1989-08-01

    Ventilation and perfusion scans were obtained in six subjects who had undergone heart-lung transplantation with consequent denervation of the cardiopulmonary axis. Two of the subjects had developed obliterative bronchiolitis, which is believed to be a form of chronic rejection. Their pulmonary function tests demonstrated airflow obstruction and their scintigraphic studies were abnormal. In the remaining four subjects without obstructive airways disease, ventilation and planar perfusion scans were normal. Single photon emission computed tomography imaging of pulmonary perfusion in these patients revealed a layered distribution of blood flow indistinguishable from that of normal individuals. It is concluded that neurogenic mechanisms have little influence on the pattern of local pulmonary blood flow at rest.

  1. Dual-energy lung perfusion and ventilation CT in children.

    PubMed

    Goo, Hyun Woo

    2013-03-01

    Dual-energy thoracic CT provides two key insights into lung physiology, i.e. regional perfusion and ventilation, and has been actively investigated to find clinically relevant applications since the introduction of dual-source CT. This functional information provided by dual-energy thoracic CT is supplementary because high-resolution thoracic anatomy is entirely preserved on dual-energy thoracic CT. In addition, virtual non-contrast imaging can omit pre-contrast scanning. In this respect, dual-energy CT imaging technique is at least dose-neutral, which is a critical requirement for paediatric imaging. In this review, imaging protocols, analysis methods, clinical applications and diagnostic pitfalls of dual-energy thoracic CT for evaluating lung perfusion and ventilation in children are described.

  2. Pretreatment with perfluorohexane vapor attenuates fMLP-induced lung injury in isolated perfused rabbit lungs.

    PubMed

    Bleyl, Jörg U; Heller, Axel R; Fehrenbach, Antonia; Heintz, Manuel; Fehrenbach, Heinz; Klenz, Gesa; Gama de Abreu, Marcelo; Hübler, Matthias; Spieth, Peter M; Koch, Thea

    2010-08-01

    The authors investigated the protective effects and dose dependency of perfluorohexane (PFH) vapor on leukocyte-mediated lung injury in isolated, perfused, and ventilated rabbit lungs. Lungs received either 18 vol.% (n = 7), 9 vol.% (n = 7), or 4.5 vol.% (n = 7) PFH. Fifteen minutes after beginning of PFH application, lung injury was induced with formyl-Met-Leu-Phe (fMLP). Control lungs (n = 7) received fMLP only. In addition 5 lungs (PFH-sham) remained uninjured receiving 18 vol.% PFH only. Pulmonary artery pressure (mPAP), peak inspiratory pressure (P(max)), and lung weight were monitored for 90 minutes. Perfusate samples were taken at regular intervals for analysis and representative lungs were fixed for histological analysis. In the control, fMLP application led to a significant increase of mPAP, P(max), lung weight, and lipid mediators. Pretreatment with PFH attenuated the rise in these parameters. This was accompanied by preservation of the structural integrity of the alveolar architecture and air-blood barrier. In uninjured lungs, mPAP, P(max), lung weight, and lipid mediator formation remained uneffected in the presence of PFH. The authors concluded that pretreatment with PFH vapor leads to an attenuation of leukocyte-mediated lung injury. Vaporization of perfluorocarbons (PFCs) offers new therapeutic options, making use of their protective and anti-inflammatory properties in prophylaxis or in early treatment of acute lung injury.

  3. Utilization of the organ care system as ex-vivo lung perfusion after cold storage transportation.

    PubMed

    Mohite, P N; Maunz, O; Popov, A-F; Zych, B; Patil, N P; Simon, A R

    2015-11-01

    The Organ Care System (OCS) allows perfusion and ventilation of the donor lungs under physiological conditions. Ongoing trials to compare preservation with OCS Lung with standard cold storage do not include donor lungs with suboptimal gas exchange and donor lungs treated with OCS following cold storage transportation. We present a case of a 48-yr-old man who received such lungs after cold storage transportation treated with ex-vivo lung perfusion utilizing OCS. © The Author(s) 2015.

  4. Perfusion lung scan: an aid in detection of lymphangitic carcinomatosis

    SciTech Connect

    Bates, S.E.; Tranum, B.L.

    1982-07-15

    Lymphangitic carcinomatosis is usually a late manifestation of metastatic disease. The patient usually presents with cough or dyspnea, and the chest radiograph is often nondiagnostic. Two patients are presented who developed symptoms while on adjuvant chemotherapy. Both had abnormal perfusion lung scans. One had matching ventilation defects; the other a normal ventilation study. Biopsy revealed metastatic carcinoma; in one case tumor was seen in both the pulmonary lymphatics and arterioles; in technique which can speed diagnosis and institution of therapy in lymphangitic carcinomatosis.

  5. Perfusion lung scan: an aid in detection of lymphangitic carcinomatosis

    SciTech Connect

    Bates, S.E.; Tranum, B.L.

    1982-07-15

    Lymphangitic carcinomatosis is usually a late manifestation of metastatic disease. The patient usually presents with cough or dyspnea, and the chest radiograph is often nondiagnostic. Two patients are presented who developed symptoms while on adjuvant chemotherapy. Both had abnormal perfusion lung scans. One had matching ventilation defects; the other a normal ventilation study. Biopsy revealed metastatic carcinoma; in one case tumor was seen in both the pulmonary lymphatics and arterioles; in the other, tumor was identified but the site could not be specified. The radionuclide lung scan is a technique which can speed diagnosis and institution of therapy in lymphangitic carcinomatosis.

  6. A physiologic and biochemical profile of clinically rejected lungs on a normothermic ex vivo lung perfusion platform.

    PubMed

    George, Timothy J; Arnaoutakis, George J; Beaty, Claude A; Jandu, Simran K; Santhanam, Lakshmi; Berkowitz, Dan E; Shah, Ashish S

    2013-07-01

    Although ex vivo lung perfusion (EVLP) is increasingly being used to evaluate and manipulate potential donor lungs before lung transplantation (LTx), data on the biochemistry of lungs during EVLP are limited. In this study, we examined the physiology and biochemistry of human lungs on an EVLP circuit. We recovered unallocated double lungs in standard fashion and split them into single lungs. All lungs received a nebulized arginase inhibitor, 2-S-amino-6-boronohexanoic acid (ABH), at either the onset (n = 6) or after 3 h (n = 8) of EVLP. Serial biochemical analysis included levels of arginase, endogenous nitric oxide synthase (eNOS), cyclic guanosine monophosphate, and reactive oxygen species. We considered lungs transplantable if they sustained a PaO2:FiO2 ≥ 350 in addition to stable pulmonary function during EVLP. We recovered a total of 14 single lungs. We deemed three single lungs from different donors to be transplantable after EVLP. These lungs had superior oxygenation, lower carbon dioxide, and more stable pulmonary artery pressures. Transplantable lungs had higher baseline levels of eNOS and higher final levels of cyclic guanosine monophosphate than non-transplantable lungs. Early ABH administration was associated with a transient increase in dynamic compliance. In this biochemical characterization of lungs deemed unsuitable for LTx, early levels of eNOS and late levels of cyclic guanosine monophosphate appear to be associated with improved allograft function during EVLP. In addition, nebulized ABH is associated with a significant increase in dynamic compliance. These data suggest that biochemical markers during EVLP may predict acceptable allograft function, and that this platform can be used to biochemically manipulate donor lungs before LTx. Copyright © 2013 Elsevier Inc. All rights reserved.

  7. Reconditioning of lungs donated after circulatory death with normothermic ex vivo lung perfusion.

    PubMed

    Nakajima, Daisuke; Chen, Fengshi; Yamada, Tetsu; Sakamoto, Jin; Ohsumi, Akihiro; Bando, Toru; Date, Hiroshi

    2012-02-01

    The use of donation-after-circulatory-death (DCD) donors for lung transplantation has come into practice. In this study we investigated whether DCD lungs can be resuscitated after warm ischemia with normothermic ex vivo lung perfusion (EVLP). Four hours after cardiac arrest, beagle dogs were divided into two groups (n = 6 each): those with static cold storage (SCS group) and those with normothermic EVLP (EVLP group), for 3.5 hours. Physiologic lung functions were evaluated during EVLP. In both groups, the left lungs were then transplanted and reperfused for 4 hours to evaluate post-transplant lung functions. Lung tissue adenosine triphosphate (ATP) levels were measured at given time-points. Lung oxygenation was significantly improved with EVLP (p < 0.01), and lung oxygenation at the end of EVLP significantly reflected post-transplant lung oxygenation (r = 0.99, p < 0.01). Post-transplant lung oxygenation was significantly better in the EVLP group than in the SCS group (p < 0.05). Both dynamic pulmonary compliance and wet-to-dry lung weight ratio 4 hours after transplantation were also significantly better in the EVLP group than in the SCS group (p < 0.05). Microthrombi in the donor lungs before transplantation were microscopically detected more often in the SCS group. The lung tissue ATP levels 4 hours after transplantation were significantly higher in the EVLP group compared with the SCS group (p = 0.03). Normothermic ex vivo lung perfusion could resuscitate DCD lungs injured by warm ischemia, and may ameliorate ischemia-reperfusion injury. Copyright © 2012 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

  8. Extravascular Lung Water and Tissue Perfusion Biomarkers After Lung Resection Surgery Under a Normovolemic Fluid Protocol.

    PubMed

    Assaad, Sherif; Kyriakides, Tassos; Tellides, George; Kim, Anthony W; Perkal, Melissa; Perrino, Albert

    2015-08-01

    The optimal fluid management for lung resection surgery remains undefined. Concern related to postoperative pulmonary edema has led to the practice of fluid restriction. This practice risks hypovolemia and tissue hypoperfusion. The authors examined the extravascular lung water accumulation and tissue perfusion biomarkers under protective lung ventilation and normovolemia. A prospective observational study. A single-center study. Forty patients aged 18 years or older undergoing lung resection surgery. Patients were maintained on protective lung ventilation and a normovolemic fluid protocol. Hemodynamic variables, including global end-diastolic volume index, cardiac index, and extravascular lung water index, together with tissue perfusion biomarkers, including serum creatinine, lactic acid, central venous oxygen saturation, and brain natriuretic peptide, were measured perioperatively. Parametric or nonparametric techniques were used to assess changes of these parameters over 72 hours postoperatively. The global end-diastolic volume index was maintained; cardiac index was increased, without a significant change in extravascular lung water index. Acute kidney injury based on AKIN criteria occurred in 3 patients (7.5%), and in 1 patient (2.5 %) based on RIFLE criteria. Lactic acid and central venous oxygen saturation remained within normal limits, and brain natriuretic peptide showed an insignificant increase. In patients undergoing lesser lung resections, a fluid protocol targeting normovolemia together with protective lung ventilation did not increase extravascular lung water. These results suggest further study to identify the optimal fluid regimen to mitigate pulmonic and extrapulmonic complications after lung resection. Published by Elsevier Inc.

  9. Pressure- and flow-controlled media perfusion differently modify vascular mechanics in lung decellularization.

    PubMed

    da Palma, Renata K; Campillo, Noelia; Uriarte, Juan J; Oliveira, Luis V F; Navajas, Daniel; Farré, Ramon

    2015-09-01

    Organ biofabrication is a potential future alternative for obtaining viable organs for transplantation. Achieving intact scaffolds to be recellularized is a key step in lung bioengineering. Perfusion of decellularizing media through the pulmonary artery has shown to be effective. How vascular perfusion pressure and flow vary throughout lung decellularization, which is not well known, is important for optimizing the process (minimizing time) while ensuring scaffold integrity (no barotrauma). This work was aimed at characterizing the pressure/flow relationship at the pulmonary vasculature and at how effective vascular resistance depends on pressure- and flow-controlled variables when applying different methods of media perfusion for lung decellularization. Lungs from 43 healthy mice (C57BL/6; 7-8 weeks old) were investigated. After excision and tracheal cannulation, lungs were inflated at 10 cmH2O airway pressure and subjected to conventional decellularization with a solution of 1% sodium dodecyl sulfate (SDS). Pressure (PPA) and flow (V'PA) at the pulmonary artery were continuously measured. Decellularization media was perfused through the pulmonary artery: (a) at constant PPA=20 cmH2O or (b) at constant V'PA=0.5 and 0.2 ml/min. Effective vascular resistance was computed as Rv=PPA/V'PA. Rv (in cmH2O/(ml/min)); mean±SE) considerably varied throughout lung decellularization, particularly for pressure-controlled perfusion (from 29.1±3.0 in baseline to a maximum of 664.1±164.3 (p<0.05), as compared with flow-controlled perfusion (from 49.9±3.3 and 79.5±5.1 in baseline to a maximum of 114.4±13.9 and 211.7±70.5 (p<0.05, both), for V'PA of 0.5 and 0.2 ml/min respectively. Most of the media infused to the pulmonary artery throughout decellularization circulated to the airways compartment across the alveolar-capillary membrane. This study shows that monitoring perfusion mechanics throughout decellularization provides information relevant for optimizing the process

  10. Ventilation/perfusion mismatch during lung aeration at birth.

    PubMed

    Lang, Justin A R; Pearson, James T; te Pas, Arjan B; Wallace, Megan J; Siew, Melissa L; Kitchen, Marcus J; Fouras, Andreas; Lewis, Robert A; Wheeler, Kevin I; Polglase, Graeme R; Shirai, Mikiyasu; Sonobe, Takashi; Hooper, Stuart B

    2014-09-01

    At birth, the transition to newborn life is triggered by lung aeration, which stimulates a large increase in pulmonary blood flow (PBF). Current theories predict that the increase in PBF is spatially related to ventilated lung regions as they aerate after birth. Using simultaneous phase-contrast X-ray imaging and angiography we investigated the spatial relationships between lung aeration and the increase in PBF after birth. Six near-term (30-day gestation) rabbits were delivered by caesarean section, intubated and an intravenous catheter inserted, before they were positioned for X-ray imaging. During imaging, iodine was injected before ventilation onset, after ventilation of the right lung only, and after ventilation of both lungs. Unilateral ventilation increased iodine levels entering both left and right pulmonary arteries (PAs) and significantly increased heart rate, iodine ejection per beat, diameters of both left and right PAs, and number of visible vessels in both lungs. Within the 6th intercostal space, the mean gray level (relative measure of iodine level) increased from 68.3 ± 11.6 and 70.3 ± 7.5%·s to 136.3 ± 22.6 and 136.3 ± 23.7%·s in the left and right PAs, respectively. No differences were observed between vessels in the left and right lungs, despite the left lung not initially being ventilated. The increase in PBF at birth is not spatially related to lung aeration allowing a large ventilation/perfusion mismatch, or pulmonary shunting, to occur in the partially aerated lung at birth.

  11. Does perfusion CT play a role in the evaluation of percutaneous microwave-ablated lung tumours?

    PubMed

    Parvizi, N; Chung, D; Little, M W; Gleeson, F V; Anderson, E M

    2016-11-01

    To assess the clinical utility of perfusion computed tomography (pCT) parameters in microwave ablation (MWA) of lung tumours. Patients were included who had primary or metastatic lung tumours and underwent pCT studies immediately pre- and post-MWA. Perfusion maps of the tumours were constructed using CT perfusion software (GE, Milwaukee, WI, USA). Regions of interest were drawn on sequential axial sections to extract the pCT parameters, blood volume (BV), average blood flow (BF), and mean transit time (MTT) from the entire tumour volume. Direct visualisation of perfusion maps were performed by two experienced readers blinded to outcome. Data were analysed using the Mann-Whitney test. Thirty-one patients with 34 lung tumours had follow-up data at 12 months. The median tumour diameter was 19 mm (10-52 mm). Seven patients developed local tumour progression (LTP) at 12 months. There was no statistical difference between patients with LTP and complete treatment based on quantitative pCT parameters. Using radiologist visualisation of perfusion maps, there was moderate agreement between the two readers (kappa coefficient 0.53) with a combined 96% sensitivity, 62% specificity, 91% positive predictive value, and 80% negative predictive value. Quantitative pCT parameters do not help differentiate between LTP and complete treatment, but subjective analysis of perfusion maps may be a useful assessment tool for identifying treatment adequacy potentially enabling identification of areas requiring further treatment at the time of the procedure. Copyright © 2016 The Royal College of Radiologists. All rights reserved.

  12. PREOPERATIVE PREDICTION OF LUNG FUNCTION IN PNEUMONECTOMY BY SPIROMETRY AND LUNG PERFUSION SCINTIGRAPHY

    PubMed Central

    Cukic, Vesna

    2012-01-01

    Introduction: Nowadays an increasing number of lung resections are being done because of the rising prevalence of lung cancer that occurs mainly in patients with limited lung function, what is caused by common etiologic factor - smoking cigarettes. Loss of lung tissue in such patients can worsen much the postoperative pulmonary function. So it is necessary to asses the postoperative pulmonary function especially after maximal resection, i.e. pneumonectomy. Objective: To check over the accuracy of preoperative prognosis of postoperative lung function after pneumonectomy using spirometry and lung perfusion scinigraphy. Material and methods: The study was done on 17 patients operated at the Clinic for thoracic surgery, who were treated previously at the Clinic for Pulmonary Diseases “Podhrastovi” in the period from 01. 12. 2008. to 01. 06. 2011. Postoperative pulmonary function expressed as ppoFEV1 (predicted postoperative forced expiratory volume in one second) was prognosticated preoperatively using spirometry, i.e.. simple calculation according to the number of the pulmonary segments to be removed and perfusion lung scintigraphy. Results: There is no significant deviation of postoperative achieved values of FEV1 from predicted ones obtained by both methods, and there is no significant differences between predicted values (ppoFEV1) obtained by spirometry and perfusion scintigraphy. Conclusion: It is necessary to asses the postoperative pulmonary function before lung resection to avoid postoperative respiratory failure and other cardiopulmonary complications. It is absolutely necessary for pneumonectomy, i.e.. maximal pulmonary resection. It can be done with great possibility using spirometry or perfusion lung scintigraphy. PMID:23378687

  13. Histologic and functional evaluation of lungs reconditioned by ex vivo lung perfusion.

    PubMed

    Medeiros, Israel Lopes; Pêgo-Fernandes, Paulo Manuel; Mariani, Alessandro Wasum; Fernandes, Flávio Guimarães; do Vale Unterpertinger, Fernando; Canzian, Mauro; Jatene, Fabio Biscegli

    2012-03-01

    Only about 15% of donor lungs are considered suitable for transplantation (LTx). Ex vivo lung perfusion (EVLP) has been developed as a method to reassess and repair damaged lungs. We report our experience with EVLP in non-acceptable donor lungs and evaluate its ability to recondition these lungs. We studied lungs from 16 brain-dead donors rejected for LTx. After harvesting, the lungs were stored at 4°C for 10 hours and subjected to normothermic EVLP with Steen Solution (Vitrolife, Göteborg, Sweden) for 60 minutes. For functional evaluation, the following variables were assessed: partial pressure of arterial oxygen (Pao(2)), pulmonary vascular resistance (PVR), and lung compliance (LC). For histologic assessment, lung biopsy was done before harvest and after EVLP. Tissue samples were examined under light microscopy. To detect and quantify apoptosis, terminal deoxynucleotide transferase-mediated deoxy uridine triphosphate nick-end labeling assay was used. Thirteen lung donors were refused for having impaired lung function. The mean Pao(2) obtained in the organ donor at the referring hospital was 193.7 mm Hg and rose to 489 mm Hg after EVLP. During EVLP, the mean PVR was 652.5 dynes/sec/cm(5) and the mean LC was 48 ml/cm H(2)O. There was no significant difference between the mean Lung Injury Score before harvest and after EVLP. There was a trend toward a reduction in the median number of apoptotic cells after EVLP. EVLP improved lung function (oxygenation capacity) of organs considered unsuitable for transplantation. Lung tissue structure did not deteriorate even after 1 hour of normothermic perfusion. Copyright © 2012 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

  14. Distribution of lung blood on modified bilateral Glenn shunt evaluated by Tc-99m-MAA lung perfusion scintigraphy

    PubMed Central

    Si, Biao; Luan, Zhao-sheng; Wang, Tong-jian; Ning, Yan-song; Li, Na; Zhu, Meng; Liu, Zhong-min; Ding, Guang-hong; Qiao, Bin

    2016-01-01

    Abstract The aim of the present study was to determine the distribution of lung blood in a modified bilateral Glenn procedure designed in our institute with lung perfusion scintigraphy. Sixteen consecutive patients who underwent modified bilateral Glenn operation from 2011 to 2014 were enrolled in the study. The control group consisted of 7 patients who underwent bidirectional Glenn shunt. Radionuclide lung perfusion scintigraphy was performed using Tc-99m-macro aggregated albumin (MAA) in all patients. For the patients in modified bilateral Glenn group, the time at which the radioactivity accumulation peaked did not differ significantly between the right and left lung field (t = 0.608, P = 0.554). The incidence of perfusion abnormality in each lung lobe also did not differ significantly (P = 0.426 by Fisher exact test). The radioactive counts were higher in the right lung than in the left lung, but the difference was not statistically significant (t = 1.502, P = 0.157). Radioactive perfusion in the lower lung field was significantly greater than that in the upper field (t = 4.368, P < 0.001). Compared with that in the bidirectional Glenn group, the ratio of radioactivity in the right lung to that in left lung was significantly lower in the modified bilateral Glenn group (t = 3.686, P = 0.002). Lung perfusion scintigraphy confirmed the benefit of the modified bilateral Glenn shunt with regard to more balanced blood perfusion in both lungs. PMID:27661042

  15. Pulmonary hypertension leads to a loss of gravity dependent redistribution of regional lung perfusion: a SPECT/CT study.

    PubMed

    Lau, Edmund Mt; Bailey, Dale L; Bailey, Elizabeth A; Torzillo, Paul J; Roach, Paul J; Schembri, Geoffrey P; Corte, Tamera J; Celermajer, David S

    2014-01-01

    Pre-capillary pulmonary hypertension (PHT) is characterised by progressive pulmonary vascular obliteration and loss of vascular reserves. In health, regional lung perfusion redistributes under the influence of gravity due to the presence of recruitable vessels. We investigated a combined single photon emission computed tomography/CT (SPECT/CT) method for assessing the pulmonary circulation by quantifying the gravity dependent redistribution of lung perfusion. Characterisation of patients versus healthy controls. 15 patients with pre-capillary PHT and 11 healthy controls. University hospital clinic. Regional lung perfusion was measured using SPECT/CT in two different postures (supine vs upright). A perfusion redistribution index (PRI) was used to quantify the cranial-caudal shift in regional lung perfusion resulting from gravitational (postural) change. PRI was compared between cases and controls, and correlated with markers of disease severity in cases. Patients with pre-capillary PHT had notably reduced PRI compared to controls (0.02±0.06 vs. 0.28±0.15 normalised perfusion/cm, p<0.0001). PRI was significantly associated with prognostic parameters such as 6 min walk distance (r=0.60, p=0.018), functional class (p=0.008), and tricuspid annular plane systolic excursion (r=0.58, p=0.022). The receiver operating characteristic curve showed that PRI differentiated patients with pre-capillary PHT from controls with AUC=0.94 (p<0.001). With SPECT/CT, gravity dependent redistribution of lung perfusion can be quantified using the PRI derived from supine and upright perfusion analysis. The potential utility of PRI for the non-invasive detection of PHT and assessment of disease severity warrants further study.

  16. Evaluating acellular versus cellular perfusate composition during prolonged ex vivo lung perfusion after initial cold ischaemia for 24 hours.

    PubMed

    Becker, Simon; Steinmeyer, Jasmin; Avsar, Murat; Höffler, Klaus; Salman, Jawad; Haverich, Axel; Warnecke, Gregor; Ochs, Matthias; Schnapper, Anke

    2016-01-01

    Normothermic ex vivo lung perfusion (EVLP) has developed as a powerful technique to evaluate particularly marginal donor lungs prior to transplantation. In this study, acellular and cellular perfusate compositions were compared in an identical experimental setting as no consensus has been reached on a preferred technique yet. Porcine lungs underwent EVLP for 12 h on the basis of an acellular or a cellular perfusate composition after 24 h of cold ischaemia as defined organ stress. During perfusion, haemodynamic and respiratory parameters were monitored. After EVLP, the lung condition was assessed by light and transmission electron microscopy. Aerodynamic parameters did not show significant differences between groups and remained within the in vivo range during EVLP. Mean oxygenation indices were 491 ± 39 in the acellular group and 513 ± 53 in the cellular group. Groups only differed significantly in terms of higher pulmonary artery pressure and vascular resistance in the cellular group. Lung histology and ultrastructure were largely well preserved after prolonged EVLP and showed only minor structural alterations which were similarly present in both groups. Prolonged acellular and cellular EVLP for 12 h are both feasible with lungs prechallenged by ischaemic organ stress. Physiological and ultrastructural analysis showed no superiority of either acellular or cellular perfusate composition.

  17. Acute kidney injury after ex vivo lung perfusion (EVLP).

    PubMed

    Hauck, J; Osho, A; Castleberry, A; Hartwig, M; Reddy, L; Phillips-Bute, B; Swaminathan, M; Mathew, J; Stafford-Smith, M

    2014-12-01

    Ex vivo lung perfusion (EVLP) identifies viability for marginal organs but complicates and lengthens lung transplantation surgery. Preliminary evidence supports equivalency for EVLP-assisted versus traditional (non-EVLP) procedures regarding graft function, postoperative course, mortality, and survival. However, acute kidney injury (AKI), a common serious complication of lung transplantation, has not been assessed. We tested the hypothesis that EVLP-assisted and non-EVLP lung transplantations are associated with different AKI rates. Demographic, procedural, and renal data were gathered for 13 EVLP-viable lung transplantations and a non-EVLP group matched 4:1 for single versus double, pulmonary disease, and age. AKI was defined by AKI Network (AKIN) criteria and peak creatinine rise relative to baseline (Δ%Cr) during the 1st 10 postoperative days. Chi-square was performed for AKIN and 2-tailed t test for %ΔCr. Patient and procedural characteristics were similar between the groups. One non-EVLP patient required postoperative dialysis. AKI rates were also similar, as assessed by both AKIN (EVLP 7/13 (54%) vs non-EVLP 32/52 (62%); P = .61) and %ΔCr (EVLP 91 ± 81% vs non-EVLP 72 ± 62%; P = .63). We did not observe different AKI rates between EVLP-assisted and traditional lung transplant procedures. Although 1 non-EVLP patient required dialysis, AKI rates were otherwise similar. These findings further support EVLP as a strategy to expand the organ pool and reduce concerns for high-renal risk recipients. The small sample size and retrospective design are limitations. However, our sample size is similar to other reports, and it is the first to analyze AKI after EVLP-assisted lung transplantation. Larger multicenter prospective studies are needed. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. Bayesian SPECT lung imaging for visualization and quantification of pulmonary perfusion

    SciTech Connect

    Scarfone, C.; Jaszczak, R.J.; Gilland, D.R.; Greer, K.L.; Munley, M.T.; Marks, L.B.; Coleman, R.E.

    1998-12-01

    In this paper, the authors quantitatively and qualitatively examine the use of a Gibbs prior in maximum a posteriori (MAP) reconstruction of SPECT images of pulmonary perfusion using the expectation-maximization (EM) algorithm. This Bayesian approach is applied to SPECT projection data acquired from a realistic torso phantom with spherical defects in the lungs simulating perfusion deficits. Both the scatter subtraction constant (k) and the smoothing parameter beta ({beta}) characterizing the prior are varied to study their effect on image quality and quantification. Region of interest (ROI) analysis is used to compare MAP-EM radionuclide concentration estimates with those derived from a ``clinical`` implementation of filtered backprojection (CFBP), and a quantitative implementation of FBP (QFBP) utilizing nonuniform attenuation and scatter compensation. Qualitatively, the MAP-EM images contain reduced artifacts near the lung boundaries relative to the FBP implementations. Generally, the MAP-EM image`s visual quality and the ability to discern the areas of reduced radionuclide concentration in the lungs depend on the value of {beta} and the total number of iterations. For certain choices of {beta} and total iterations, MAP-EM lung images are visually comparable to FBP. Based on profile and ROI analysis, SPECT QFBP and MAP-EM images have the potential to provide quantitatively accurate reconstructions when compared to CFBP. The computational burden, however, is greater for the MAP-EM approach. To demonstrate the clinical efficacy of the methods, the authors present pulmonary images of a patient with lung cancer.

  19. Alternative solution for ex vivo lung perfusion, experimental study on donated human lungs non-accepted for transplantation.

    PubMed

    Fernandes, Lucas Matos; Mariani, Alessandro Wasum; Medeiros, Israel Lopes de; Samano, Marcos Naoyuki; Abdalla, Luís Gustavo; Correia, Aristides Tadeu; Nepomuceno, Natália Aparecida; Canzian, Mauro; Pêgo-Fernandes, Paulo Manuel

    2015-05-01

    To evaluate a new perfusate solution to be used for ex vivo lung perfusion. Randomized experimental study using lungs from rejected brain-dead donors harvested and submitted to 1 hour of ex vivo lung perfusion (EVLP) using mainstream solution or the alternative. From 16 lungs blocs tested, we found no difference on weight after EVLP: Steen group (SG) = 1,097±526g; Alternative Perfusion Solution (APS) = 743±248g, p=0.163. Edema formation, assessed by Wet/dry weigh ratio, was statistically higher on the Alternative Perfusion Solution group (APS = 3.63 ± 1.26; SG = 2.06 ± 0.28; p = 0.009). No difference on PaO2 after EVLP (SG = 498±37.53mmHg; APS = 521±55.43mmHg, p=0.348, nor on histological analyses: pulmonary injury score: SG = 4.38±1.51; APS = 4.50±1.77, p=0.881; apoptotic cells count after perfusion: SG = 2.4 ± 2.0 cells/mm2; APS = 4.8 ± 6.9 cells/mm2; p = 0.361). The ex vivo lung perfusion using the alternative perfusion solution showed no functional or histological differences, except for a higher edema formation, from the EVLP using Steen Solution(r) on lungs from rejected brain-dead donors.

  20. Effects of Constant Flow vs. Constant Pressure Perfusion on Fluid Filtration in Severe Hypothermic Isolated Blood-Perfused Rat Lungs.

    PubMed

    Halsøy, Kathrine; Kondratiev, Timofey; Tveita, Torkjel; Bjertnaes, Lars J

    2016-01-01

    Victims of severe accidental hypothermia are prone to fluid extravasation but rarely develop lung edema. We hypothesize that combined hypothermia-induced increase in pulmonary vascular resistance (PVR) and a concomitant fall in cardiac output protect the lungs against edema development. Our aim was to explore in hypothermic-isolated blood-perfused rat lungs whether perfusion at constant pressure influences fluid filtration differently from perfusion at constant flow. Isolated blood-perfused rat lungs were hanging freely in a weight transducer for measuring weight changes (ΔW). Fluid filtration coefficient (Kfc), was determined by transiently elevating left atrial pressure (Pla) by 5.8 mmHg two times each during normothermia (37°C) and during hypothermia (15°C). The lung preparations were randomized to two groups. One group was perfused with constant flow (Constant flow group) and the other group with constant pulmonary artery pressure (Constant PPA group). Microvascular pressure (Pmv) was determined before and during elevation of Pla (ΔPmv) by means of the double occlusion technique. Kfc was calculated with the formula Kfc = ΔW/ΔPmv/min. All Kfc values were normalized to predicted lung weight (PLW), which was based on body weight (BW) according to the formula: PLW = 0.0053 BW - 0.48 and presented as KfcPLW in mg/min/mmHg/g. At cessation, bronchoalveolar lavage (BAL) fluid/perfusate protein concentration (B/P) ratio was determined photometrically. Data were analyzed with parametric or non-parametric tests as appropriate. p < 0.05 considered as significant. Perfusate flow remained constant in the Constant flow group, but was more than halved during hypothermia in the Constant PPA group concomitant with a more fold increase in PVR. In the Constant flow group, KfcPLW and B/P ratio increased significantly by more than 10-fold during hypothermia concerted by visible signs of edema in the trachea. Hemoglobin and hematocrit increased within the

  1. Feasibility of quantitative lung perfusion by 4D CT imaging by a new dynamic-scanning protocol in an animal model

    NASA Astrophysics Data System (ADS)

    Wang, Yang; Goldin, Jonathan G.; Abtin, Fereidoun G.; Brown, Matt; McNitt-Gray, Mike

    2008-03-01

    The purpose of this study is to test a new dynamic Perfusion-CT imaging protocol in an animal model and investigate the feasibility of quantifying perfusion of lung parenchyma to perform functional analysis from 4D CT image data. A novel perfusion-CT protocol was designed with 25 scanning time points: the first at baseline and 24 scans after a bolus injection of contrast material. Post-contrast CT scanning images were acquired with a high sampling rate before the first blood recirculation and then a relatively low sampling rate until 10 minutes after administrating contrast agent. Lower radiation techniques were used to keep the radiation dose to an acceptable level. 2 Yorkshire swine with pulmonary emboli underwent this perfusion- CT protocol at suspended end inspiration. The software tools were designed to measure the quantitative perfusion parameters (perfusion, permeability, relative blood volume, blood flow, wash-in & wash-out enhancement) of voxel or interesting area of lung. The perfusion values were calculated for further lung functional analysis and presented visually as contrast enhancement maps for the volume being examined. The results show increased CT temporal sampling rate provides the feasibility of quantifying lung function and evaluating the pulmonary emboli. Differences between areas with known perfusion defects and those without perfusion defects were observed. In conclusion, the techniques to calculate the lung perfusion on animal model have potential application in human lung functional analysis such as evaluation of functional effects of pulmonary embolism. With further study, these techniques might be applicable in human lung parenchyma characterization and possibly for lung nodule characterization.

  2. Uptake of exogenous spermidine by rat lungs perfused in situ

    SciTech Connect

    Rannels, D.E.; Addison, J.L.

    1987-01-01

    Uptake of the polyamine spermidine (SPD) from the pulmonary circulation was characterized by using ventilated rat lungs perfused in situ with Krebs-Henseleit-bicarbonate buffer containing 4.5% bovine serum albumin, 5.6 mM glucose, and 20 amino acids at plasma levels. (/sup 14/C)SPD was accumulated by the lungs in a time- and concentration-dependent manner. The pathway of SPD uptake exhibited saturation kinetics with an apparent K/sub m/ in the range of 1 ..mu..M and a V/sub max/ of 450-540 pmol/g lung min. SPD uptake was inhibited by the naturally occurring polyamines putrescine and spermine (SPM) and by the inhibitor of polyamine synthesis, methyglyoxal bis(guanylhydrazone) (MGBG). Inhibition of SPD uptake by SPM followed competitive kinetics; although MGBG was also a competitive inhibitor of SPD uptake, MGBG was less effective than SPM. These observations indicate that SPD is taken up from the pulmonary circulation by a carrier-mediated pathway that is inhibited by other natural polyamines and by MGBG and exhibits by other natural polyamines and by MGBG and exhibits substrate affinity in the range of plasma SPD concentrations.

  3. Computerized tomography versus perfusion lung scanning in canine radiation lung injury

    SciTech Connect

    Ahmed, I.H.; Logus, J.W.; El-Khatib, E.; Battista, J.J.; Ferri, H.; Lentle, B.C.; Man, G.C.; Man, S.F. )

    1990-03-01

    Computerized tomographic (CT) measurements of lung density were obtained before and serially after thoracic irradiation in dogs to detect the alterations caused by radiation therapy. Fourteen mongrel dogs were given either 2000 cGy (Group A, 10 dogs, right lower zone irradiation), 1000 cGy (Group B, 2 dogs, right lower zone irradiation), or 500 cGy (Group C, 2 dogs, right lung irradiation) in one fraction. Once before and bi-weekly after irradiation, the anesthetized dogs had thoracic CT scans. CT numbers for the irradiated area were compared to their preirradiation control values. Macro-aggregated albumin (MAA) perfusion lung scans were also obtained before and at weekly intervals after irradiation and were evaluated visually and quantitatively for abnormalities. When both these tests were abnormal, or at the end of the scheduled study, the dogs were sacrificed to confirm radiation lung injury histologically. Our results showed that CT numbers (as a measure of tissue density) were higher with higher doses of radiation. Among all the techniques used, only the quantitative assessment of macro-aggregated albumin perfusion scan detected abnormalities in all the dogs given 2000 cGy. Their abnormalities correlated well with the presence of radiation lung damage histologically, however, the applicability of these methods in the detection of early injury has to be further evaluated.

  4. Kinetics of reversible-sequestration of leukocytes by the isolated perfused rat lung

    SciTech Connect

    Goliaei, B.

    1980-08-01

    The kinetics and morphology of sequestration and margination of rat leukocytes were studied using an isolated perfused and ventilated rat lung preparation. Whole rat blood, bone marrow suspension, or leukocyte suspensions, were used to perfuse the isolated rat lung. The lung was also perfused with latex particle suspensions and the passage of particles through the lung capillaries was studied. When a leukocyte suspension was perfused through the lung in the single-pass mode, the rate of sequestration decreased as more cells were perfused. In contrast, latex particles of a size comparable to that of leukocytes were totally stopped by the lung. When the leukocyte suspension was recirculated through the lung, cells were rapidly removed from circulation until a steady state was reached, after which no net removal of cells by the lung occurred. These results indicate that leukocytes are reversibly sequestered from circulation. The sequestered cells marginated and attached to the luminal surface of the endothelium of post-capillary venules and veins. A mathematical model was developed based on the assumption that the attachment and detachment of leukocytes to blood vessel walls follows first-order kinetics. The model correctly predicts the following characteristics of the system: (a) the kinetics of the sequestration of leukocytes by the lung; (b) the existence of a steady state when a suspension of leukocytes is recirculated through the lung; and (c) the independence of the fraction of cells remaining in circulation from the starting concentration for all values of starting concentration. (ERB)

  5. Lung Perfusion and Ventilation During Cardiopulmonary Bypass Reduces Early Structural Damage to Pulmonary Parenchyma.

    PubMed

    Freitas, Claudia Regina da Costa; Malbouisson, Luiz Marcelo Sa; Benicio, Anderson; Negri, Elnara Marcia; Bini, Filipe Minussi; Massoco, Cristina Oliveira; Otsuki, Denise Aya; Melo, Marcos Francisco Vidal; Carmona, Maria Jose Carvalho

    2016-04-01

    It is unclear whether maintaining pulmonary perfusion and ventilation during cardiopulmonary bypass (CPB) reduces pulmonary inflammatory tissue injury compared with standard CPB where the lungs are not ventilated and are minimally perfused. In this study, we tested the hypothesis that maintenance of lung perfusion and ventilation during CPB decreases regional lung inflammation, which may result in less pulmonary structural damage. Twenty-seven pigs were randomly allocated into a control group only submitted to sternotomy (n = 8), a standard CPB group (n = 9), or a lung perfusion group (n = 10), in which lung perfusion and ventilation were maintained during CPB. Hemodynamics, gas exchanges, respiratory mechanics, and systemic interleukins (ILs) were determined at baseline (T0), at the end of 90 minutes of CPB (T90), and 180 minutes after CPB (T180). Bronchoalveolar lavage (BAL) ILs were obtained at T0 and T180. Dorsal and ventral left lung tissue samples were examined for optical and electron microscopy. At T90, there was a transient reduction in PaO2/FIO2 in CPB (126 ± 64 mm Hg) compared with the control and lung perfusion groups (296 ± 46 and 244 ± 57 mm Hg; P < 0.001), returning to baseline at T180. Serum ILs were not different among the groups throughout the study, whereas there were significant increases in BAL IL-6 (P < 0.001), IL-8 (P < 0.001), and IL-10 (P < 0.001) in both CPB and lung perfusion groups compared with the control group. Polymorphonuclear counts within the lung tissue were smaller in the lung perfusion group than in the CPB group (P = 0.006). Electron microscopy demonstrated extrusion of surfactant vesicles into the alveolar spaces and thickening of the alveolar septa in the CPB group, whereas alveolar and capillary histoarchitecture was better preserved in the lung perfusion group. Maintenance of lung perfusion and ventilation during CPB attenuated early histologic signs of pulmonary inflammation and injury compared with standard CPB

  6. Usefulness of lung perfusion scintigraphy before lung cancer resection in patients with ventilatory obstruction.

    PubMed

    Mineo, Tommaso C; Schillaci, Orazio; Pompeo, Eugenio; Mineo, Davide; Simonetti, Giovanni

    2006-11-01

    The study was conducted to evaluate the efficacy of preoperative lung perfusion scintigraphy performed by planar acquisition and single-photon emission computed tomography (SPECT) in predicting postoperative pulmonary function of patients with resectable lung cancer and obstructive ventilatory defect. The study enrolled 39 patients (mean age, 67 +/- 2.1 years). All patients underwent preoperative and postoperative pulmonary function tests. Cut-off values for postoperative forced expiratory volume in 1 second (FEV1) were 65% of the predicted value for pneumonectomy and 45% for lobectomy. A semiquantitative analysis of planar and SPECT lung perfusion scintigraphy images was performed preoperatively to estimate postoperative predicted FEV1 (FEV1ppo). Relationships between FEV1ppo and measured postoperative FEV1 were tested by the Pearson correlation and Bland Altman agreement tests. Twenty-eight lobectomies and 11 pneumonectomies were performed. The FEV1ppo estimated by mean planar lung scintigraphy was 1.85 +/- 0.38 L, with a Pearson correlation coefficient to the measured FEV1 of 0.8632 (p < 0.001). The mean FEV1ppo estimated by SPECT was 1.78 +/- 0.31 L, with a Pearson coefficient to the measured FEV1 of 0.8527 (p < 0.001). Both values showed a more significant correlation with postoperative measured FEV1 after lobectomy (p < 0.001) than after pneumonectomy (p = 0.045). The Bland Altman test confirmed satisfactory agreement of FEV1ppo estimated by both planar lung scintigraphy and SPECT with FEV1 measured by spirometry. Both planar lung scintigraphy and SPECT can accurately predict postoperative FEV1 and can therefore be considered reliable tools in establishing operability of patients with lung cancer and ventilatory obstruction.

  7. Correlation of iodine uptake and perfusion parameters between dual-energy CT imaging and first-pass dual-input perfusion CT in lung cancer.

    PubMed

    Chen, Xiaoliang; Xu, Yanyan; Duan, Jianghui; Li, Chuandong; Sun, Hongliang; Wang, Wu

    2017-07-01

    To investigate the potential relationship between perfusion parameters from first-pass dual-input perfusion computed tomography (DI-PCT) and iodine uptake levels estimated from dual-energy CT (DE-CT).The pre-experimental part of this study included a dynamic DE-CT protocol in 15 patients to evaluate peak arterial enhancement of lung cancer based on time-attenuation curves, and the scan time of DE-CT was determined. In the prospective part of the study, 28 lung cancer patients underwent whole-volume perfusion CT and single-source DE-CT using 320-row CT. Pulmonary flow (PF, mL/min/100 mL), aortic flow (AF, mL/min/100 mL), and a perfusion index (PI = PF/[PF + AF]) were automatically generated by in-house commercial software using the dual-input maximum slope method for DI-PCT. For the dual-energy CT data, iodine uptake was estimated by the difference (λ) and the slope (λHU). λ was defined as the difference of CT values between 40 and 70 KeV monochromatic images in lung lesions. λHU was calculated by the following equation: λHU = |λ/(70 - 40)|. The DI-PCT and DE-CT parameters were analyzed by Pearson/Spearman correlation analysis, respectively.All subjects were pathologically proved as lung cancer patients (including 16 squamous cell carcinoma, 8 adenocarcinoma, and 4 small cell lung cancer) by surgery or CT-guided biopsy. Interobserver reproducibility in DI-PCT (PF, AF, PI) and DE-CT (λ, λHU) were relatively good to excellent (intraclass correlation coefficient [ICC]Inter = 0.8726-0.9255, ICCInter = 0.8179-0.8842; ICCInter = 0.8881-0.9177, ICCInter = 0.9820-0.9970, ICCInter = 0.9780-0.9971, respectively). Correlation coefficient between λ and AF, and PF were as follows: 0.589 (P < .01) and 0.383 (P < .05). Correlation coefficient between λHU and AF, and PF were as follows: 0.564 (P < .01) and 0.388 (P < .05).Both the single-source DE-CT and dual-input CT perfusion analysis method can be applied to

  8. [Evaluation of lung perfusion scintigraphy without ventilation scintigraphy in the diagnosis of pulmonary thromboembolism].

    PubMed

    Jurkiene, Nemira

    2002-01-01

    The role of perfusion lung scintigraphy in the diagnosis of pulmonary embolism (PE) is reviewed. During the study 227 perfusion lung scans were obtained. The scans were grouped according to the PIOPED criteria into 5 groups: normal scans, very low, low, intermediate and high PE probability. The perfusion scans were analyzed according to the original PIOPED criteria, without ventilation scans. Evidence is provided that a normal perfusion scan excludes pulmonary embolism, and that a high probability lung scan, defined as a segmental perfusion defect with locally normal chest X-ray or findings in X-ray are smaller, sufficiently confirms the presence of pulmonary embolism in the majority of these patients (92.2%).

  9. First Danish experience with ex vivo lung perfusion of donor lungs before transplantation.

    PubMed

    Henriksen, Ian Sune Iversen; Møller-Sørensen, Hasse; Møller, Christian Holdfold; Zemtsovski, Mikhail; Nilsson, Jens Christian; Seidelin, Casper Tobias; Perch, Michael; Iversen, Martin; Steinbrüchel, Daniel

    2014-03-01

    The number of lung transplantations is limited by a general lack of donor organs. Ex vivo lung perfusion (EVLP) is a novel method to optimise and evaluate marginal donor lungs prior to transplantation. We describe our experiences with EVLP in Denmark during the first year after its introduction. The study was conducted by prospective registration of donor offers and lung transplantations in Denmark from 1 May 2012 to 30 April 2013. Donor lungs without any contraindications were transplanted in the traditional manner. Taken for EVLP were donor lungs that were otherwise considered transplantable, but failed to meet the usual criteria due to possible contusions or because they were from donors with sepsis or unable to pass the oxygenation test. In the study period, seven of 33 Danish lung transplantations were made possible due to EVLP. One patient died of non-EVLP-related causes, but all other recipients were alive with normal graft function at the end of our registration period. All lungs showed an improved PaO2/FiO2 ratio from a median 23.1 kPa (8.8-38.9) within the donor to 58.8 kPa (34.9-76.5) (FiO2 = 1.0) after EVLP, which corresponds to a 155% improved oxygenation. The median time to extubation, time in intensive care unit and the admission period were 1, 7 and 39 days, respectively. In the first year after the introduction of EVLP in Denmark, seven pairs of donor lungs that previously would have been rejected have been transplanted as a result of their improved function. EVLP seems to be a safe way to increase the use of marginal donor lungs. no funding was granted for the present paper. not relevant.

  10. Doppler flow evaluation can anticipate abnormal left lung perfusion after transcatheter closure of patent ductus arteriosus.

    PubMed

    Soares, Andressa M; Aiello, Vera D; Andrade, José L; Kajita, Luis J; Soares, José; Morhy, Samira S; Mathias, Wilson; Lopes, Antonio A B; Ramires, José A F

    2004-11-01

    Coil protrusion into the left pulmonary artery (LPA) has been described after transcatheter closure of the patent ductus arteriosus (PDA). The possible impact of such a finding in lung perfusion has not been completely clarified. We evaluated Doppler flow velocities and lung perfusion in patients submitted to that procedure. After transcatheter closure of PDA with coils, 70 patients (mean age 8.6+/-3.4 years) were followed for a period of 3.6+/-0.9 years (range 2.1-5.9) and compared to 22 controls. Peak flow velocities and coil protrusion were assessed by Doppler echocardiography. A Doppler velocity index (DVI) was calculated by the difference between the LPA and right pulmonary artery (RPA) peak flow velocities relative to the pulmonary trunk (PT) expressed in percentage, as follows: DVI=(LPA velocity - RPA velocity)/PT velocity x 100. Lung scintigraphy was performed using (99m)Tc-labelled macro-aggregated albumin. Device protrusion was observed in 94% of the patients, 10% of whom presented abnormal left lung perfusion. Peak LPA velocity and DVI were significantly greater in patients (p=0.001) and correlated negatively with left lung perfusion values (R(2)=0.21 and R(2)=0.65, respectively). A cut-off value of 50% for the DVI showed high sensitivity and specificity for reduced lung perfusion. Impaired left lung perfusion may appear following transcatheter closure of PDA with coils and the determination of DVI may anticipate such alteration.

  11. Graft downsizing during ex vivo lung perfusion: case report and technical notes.

    PubMed

    Nosotti, M; Rosso, L; Mendogni, P; Tosi, D; Palleschi, A; Righi, I; Froio, S; Valenza, F; Santambrogio, L

    2014-09-01

    Among patients with respiratory insufficiency awaiting lung transplantation, small adult patients have a lower opportunity of receiving size-matched pulmonary grafts, because of the shortage of donors, particularly those of small size. Reducing the size of an oversized graft is one of the methods to increase the donor pool; similarly, ex vivo lung perfusion is an emerging technique aimed toward the same purpose. We describe how we combined the 2 techniques (lobar transplantation plus contralateral nonanatomic graft reduction during ex vivo lung perfusion) to overcome graft shortage in a clinical case. For the 1st time, this case report demonstrates that surgical manipulation during ex vivo lung perfusion does not affect the functional improvement in a lung previously judged to be not suitable for transplantation. The 6-month follow-up results are similar to those of standard bilateral lung transplantation.

  12. Radiation injury in rat lung: I. Prostacyclin (PGI/sub 2/) production, arterial perfusion, and ultrastructure

    SciTech Connect

    Ts'ao, C.; Ward, W.F.; Port, C.D.

    1983-11-01

    Pulmonary prostacyclin (PGI/sub 2/) production, arterial perfusion, and ultrastructure were correlated in rats sacrificed from 1 day to 6 months after a single exposure of 25 Gy of gamma rays to the right hemithorax. PGI/sub 2/ production by the irradiated lung decreased to approximately half the normal value 1 day after irradiation (P < 0.05), then increased steadily throughout the study. By 6 months postirradiation, the right lung produced two to three times as much PGI/sub 2/ as did either shielded left lung or sham-irradiated lungs (P < 0.05). Perfusion scans revealed hyperemia of the right lung from 1 to 14 days after irradiation. From its peak at 14 days postirradiation, however, perfusion of the irradiated lung decreased steadily, then reached a plateau from 3 to 6 months at less than half that in the shielded left lung. Electron micrographs of the right lung revealed perivascular edema from 1 to 30 days after irradiation. The right lung then exhibited changes typical of radiation pneumonitis followed by progressive interstitial fibrosis. Platelet aggregates were not observed at any time. Thus, decreased PGI/sub 2/ production is an immediate but transient response of the lung to radiation injury. Then from 2 to 6 months after irradiation, the fibrotic, hypoperfused lung produces increasing amounts of the potent vasodilator and antithrombotic agent, PGI/sub 2/. Pulmonary PGI/sub 2/ production and arterial perfusion are inversely correlated for at least 6 months after hemithoracic irradiation.

  13. Steal phenomenon-induced lung perfusion defects in pulmonary arteriovenous fistulas: assessment with automated perfusion SPECT-CT fusion images.

    PubMed

    Suga, Kazuyoshi; Iwanaga, Hideyuki; Tokuda, Osamu; Okada, Munemasa; Tanaka, Nobuyuki; Matsunaga, Naofumi

    2010-09-01

    Lung perfusion impairment in patients with pulmonary arteriovenous fistula (AVF) was evaluated by automated deep inspiratory breath-hold (DIBrH) perfusion single-photon emission computed tomography (SPECT)-CT fusion images. Participants were 14 patients with a single (N=6) or multiple nodular AVFs (N=8) diagnosed by contrast-enhanced CT scan and/or pulmonary angiography. After the injection of 185MBq Tc-99m-macroaggregated albumin, a whole-body scan was obtained to quantify an intrapulmonary right-to-left shunt. Subsequently, DIBrH SPECT was obtained using the continuous rotating acquisition mode of a dual-headed SPECT system, which was automatically coregistered with DIBrH CT. The anatomic relationship between AVF and perfusion defects was assessed on the fusion images. The whole-body scan depicted systemic organs indicating the presence of an intrapulmonary right-to-left shunt in all the patients. DIBrH SPECT showed 34 perfusion defects in these patients, which were located at the AVF and in the surrounding lungs of the AVF on the fusion images, regardless of the absence of morphologic abnormality on CT in all the patients. These defects were considered to be caused by the 'steal phenomenon' associated with the high and fast pulmonary arterial flow to each AVF, which were more extensive and severe in the multiple AVFs compared with a single AVF (P=0.0012), occasionally extending to the entire lobe with AVF or even to the adjacent lobe. In five patients, the fusion images detected a total of six tiny AVFs with unexpectedly extensive 'steal phenomenon'-induced defects, which had been missed by other radiological imaging techniques. The summed value of the shunt index estimated by the whole-body scan and the lung perfusion defect extent estimated by DIBrH SPECT was significantly correlated with PaO2 in all the patients (P < 0.0001), with a better correlation compared with the shunt index alone. In addition to the right-to-left shunt, 'steal phenomenon

  14. Positron emission tomography to assess hypoxia and perfusion in lung cancer

    PubMed Central

    Verwer, Eline E; Boellaard, Ronald; van der Veldt, Astrid AM

    2014-01-01

    In lung cancer, tumor hypoxia is a characteristic feature, which is associated with a poor prognosis and resistance to both radiation therapy and chemotherapy. As the development of tumor hypoxia is associated with decreased perfusion, perfusion measurements provide more insight into the relation between hypoxia and perfusion in malignant tumors. Positron emission tomography (PET) is a highly sensitive nuclear imaging technique that is suited for non-invasive in vivo monitoring of dynamic processes including hypoxia and its associated parameter perfusion. The PET technique enables quantitative assessment of hypoxia and perfusion in tumors. To this end, consecutive PET scans can be performed in one scan session. Using different hypoxia tracers, PET imaging may provide insight into the prognostic significance of hypoxia and perfusion in lung cancer. In addition, PET studies may play an important role in various stages of personalized medicine, as these may help to select patients for specific treatments including radiation therapy, hypoxia modifying therapies, and antiangiogenic strategies. In addition, specific PET tracers can be applied for monitoring therapy. The present review provides an overview of the clinical applications of PET to measure hypoxia and perfusion in lung cancer. Available PET tracers and their characteristics as well as the applications of combined hypoxia and perfusion PET imaging are discussed. PMID:25493221

  15. Altered Immunogenicity of Donor Lungs via Removal of Passenger Leukocytes Using Ex Vivo Lung Perfusion.

    PubMed

    Stone, J P; Critchley, W R; Major, T; Rajan, G; Risnes, I; Scott, H; Liao, Q; Wohlfart, B; Sjöberg, T; Yonan, N; Steen, S; Fildes, J E

    2016-01-01

    Passenger leukocyte transfer from the donor lung to the recipient is intrinsically involved in acute rejection. Direct presentation of alloantigen expressed on donor leukocytes is recognized by recipient T cells, promoting acute cellular rejection. We utilized ex vivo lung perfusion (EVLP) to study passenger leukocyte migration from donor lungs into the recipient and to evaluate the effects of donor leukocyte depletion prior to transplantation. For this purpose, female pigs received male left lungs either following 3 h of EVLP or retrieved using standard protocols. Recipients were monitored for 24 h and sequential samples were collected. EVLP-reduced donor leukocyte transfer into the recipient and migration to recipient lymph nodes was markedly reduced. Recipient T cell infiltration of the donor lung was significantly diminished via EVLP. Donor leukocyte removal during EVLP reduces direct allorecognition and T cell priming, diminishing recipient T cell infiltration, the hallmark of acute rejection. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

  16. Ventilation/perfusion lung scan in pulmonary veno-occlusive disease.

    PubMed

    Seferian, Andrei; Helal, Badia; Jaïs, Xavier; Girerd, Barbara; Price, Laura C; Günther, Sven; Savale, Laurent; Dorfmüller, Peter; Parent, Florence; Sitbon, Olivier; Humbert, Marc; Simonneau, Gérald; Montani, David

    2012-07-01

    Pulmonary veno-occlusive disease (PVOD), a rare form of pulmonary arterial hypertension (PAH), requires histological proof for definitive diagnosis; however, lung biopsy is not recommended in PAH. Recent conjoint European Respiratory Society/European Society of Cardiology guidelines suggest that nonmatched perfusion defects on ventilation/perfusion (V'/Q') lung scanning in PAH patients may suggest PVOD. The aim of our study was to evaluate V'/Q' lung scans in a large cohort of PVOD and idiopathic or heritable PAH patients. V'/Q' lung scans from 70 patients with idiopathic or heritable PAH and 56 patients with confirmed or highly probable PVOD were reviewed in a double-blind manner. The vast majority of V'/Q' lung scans were normal or without significant abnormalities in both groups. No differences in ventilation or perfusion lung scans were observed between PAH and PVOD patients (all p>0.05). Furthermore, no differences were observed between confirmed (n=31) or highly probable PVOD (n=25). Nonmatched perfusion defects were found in seven (10%) idiopathic PAH patients and four (7.1%) PVOD patients (p>0.05). Nonmatched perfusion defects were rarely seen in a large cohort of idiopathic or heritable PAH and PVOD patients. Future recommendations should be amended according to these results suggesting that V'/Q' lung scanning is not useful in discriminating PVOD from idiopathic PAH.

  17. Evaluation of Primary Pulmonary Vein Stenosis in Children: Comparison of Radionuclide Perfusion Lung Scan and Angiography.

    PubMed

    Drubach, Laura A; Jenkins, Kathy J; Stamoulis, Catherine; Palmer, Edwin L; Lee, Edward Y

    2015-10-01

    The purpose of this study was to evaluate the utility of radionuclide perfusion lung scanning in the evaluation of primary pulmonary vein stenosis (PVS) in pediatric patients by comparing it with angiography. We retrospectively identified pediatric patients with primary PVS who underwent both lung scanning and angiography. A cohort of 34 patients was evaluated. The presence of PVS in the right upper, right lower, left upper, and left lower pulmonary veins on angiograms was recorded. Two nuclear medicine physicians evaluated the lung scans for perfusion defects. Agreement between lung scan and angiographic findings was assessed with contingency tables. Sensitivity and specificity of lung scanning for accurate detection of PVS with angiographic findings as the reference standard were assessed by ROC analysis. Angiography depicted PVS in 90 of the total 136 pulmonary veins (66%). Lung scans correctly depicted 65 (72%) of the cases of PVS diagnosed with angiography. The sensitivity and specificity of lung scans were 76.0% and 88.9% for the right upper pulmonary vein, 70.6% and 94.1% for the right lower pulmonary vein, 77.3% and 58.3% for the left upper pulmonary vein, and 65.4% and 87.5% for the left lower pulmonary vein. Lung scan findings correlate with angiographic findings in the detection of primary PVS in pediatric patients. Perfusion lung scanning may have a role in angiographically diagnosed PVS by noninvasively showing relative perfusion at the tissue level.

  18. Arterial input function placement effect on computed tomography lung perfusion maps.

    PubMed

    Jimenez-Juan, Laura; Mehrez, Hatem; Dey, Chris; Homampour, Shabnam; Oikonomou, Anastasia; Ursani, Fatima; Paul, Narinder

    2016-02-01

    A critical source of variability in dynamic perfusion computed tomography (DPCT) is the arterial input function (AIF). However, the impact of the AIF location in lung DPCT has not been investigated yet. The purpose of this study is to determine whether the location of the AIF within the central pulmonary arteries influences the accuracy of lung DPCT maps. A total of 54 lung DPCT scans were performed in three pigs using different rates and volumes of iodinated contrast media. Pulmonary blood flow (PBF) perfusion maps were generated using first-pass kinetics in three different AIF locations: the main pulmonary trunk (PT), the right main (RM) and the left main (LM) pulmonary arteries. A total of 162 time density curves (TDCs) and corresponding PBF perfusion maps were generated. Linear regression and Spearman's rank correlation coefficient were used to compare the TDCs. PBF perfusion maps were compared quantitatively by taking twenty six regions of interest throughout the lung parenchyma. Analysis of variance (ANOVA) was used to compare the mean PBF values among the three AIF locations. Two chest radiologists performed qualitative assessment of the perfusion maps using a 3-point scale to determine regions of perfusion mismatch. The linear regression of the TDCs from the RM and LM compared to the PT had a median (range) of 1.01 (0.98-1.03). The Spearman rank correlation between the TDCs was 0.88 (P<0.05). ANOVA analysis of the perfusion maps demonstrated no statistical difference (P>0.05). Qualitative comparison of the perfusion maps resulted in scores of 1 and 2, demonstrating either identical or comparable maps with no significant difference in perfusion defects between the different AIF locations. Accurate PBF perfusion maps can be generated with the AIF located either at the PT, RM or LM pulmonary arteries.

  19. A Leukocyte Filter Does Not Provide Further Benefit During Ex Vivo Lung Perfusion.

    PubMed

    Luc, Jessica G Y; Aboelnazar, Nader S; Himmat, Sayed; Hatami, Sanaz; Haromy, Alois; Matsumura, Nobutoshi; Vasanthan, Vishnu; White, Christopher W; Mengel, Michael; Freed, Darren H; Nagendran, Jayan

    2017-02-20

    Normothermic ex vivo lung perfusion (EVLP) allows for assessment and reconditioning of donor lungs. Though a leukocyte filter (LF) is routinely incorporated into the EVLP circuit, its efficacy remains to be determined. Twelve pig lungs were perfused and ventilated ex vivo in a normothermic state for 12 hours. Lungs (n=3) were allocated to 4 groups according to perfusate composition and the presence or absence of a LF in the circuit (acellular ± LF, cellular ± LF). Acceptable physiologic lung parameters were achieved during EVLP; however, increased amounts of pro-inflammatory cytokines (TNF-α, IL-6) and leukocytes in the perfusate were observed despite the presence or absence of a LF. Analysis of cells washed off the LF demonstrates that it trapped leukocytes though was ineffective throughout perfusion as it became saturated over 12 hours. We conclude that there is no objective evidence to support the routine incorporation of a LF during EVLP as it does not provide further benefit and its removal does not appear to cause harm. The lack of hypothesized benefit to a LF may be due to the saturation of the LF with donor leukocytes, leading to similar amounts of circulating leukocytes still present in the perfusate with and without a LF.

  20. TU-G-BRA-01: Assessing Radiation-Induced Reductions in Regional Lung Perfusion Following Stereotactic Radiotherapy for Lung Cancer

    SciTech Connect

    McGurk, R; Green, R; Lawrence, M; Schreiber, E; Das, S; Zagar, T; Marks, L; Sheikh, A; McCartney, W; Rivera, P

    2015-06-15

    Purpose: The dose-dependent nature of radiation therapy (RT)-induced lung injury following hypo-fractionated stereotactic RT is unclear. We herein report preliminary results of a prospective study assessing the magnitude of RT-induced reductions in regional lung perfusion following hypo-fractionated stereotactic RT. Methods: Four patients undergoing hypo-fractionated stereotactic lung RT (SBRT: 12 Gy x 4 fractions or 10 Gy x 5 fractions) had a pre-treatment SPECT (single-photon emission computed tomography) perfusion scan providing a 3D map of regional lung perfusion. Scans were repeated 3–6 months post-treatment. Pre- and post SPECT scans were registered to the planning CT scan (and hence the 3D dose data). Changes in regional perfusion (counts per cc on the pre-post scans) were computed in regions of the lung exposed to different doses of radiation (in 5 Gy intervals), thus defining a dose-response function. SPECT scans were internally normalized to the regions receiving <5 Gy. Results: At 3 months post-RT, the changes in perfusion are highly variable. At 6 months, there is a consistent dose-dependent reduction in regional perfusion. The average percent decline in regional perfusion was 10% at 15–20 Gy, 20% at 20–25 Gy, and 30% at 25–30 Gy representing a relatively linear dose response with an approximate 2% reduction per Gray for doses in excess of 10 Gy. There was a subtle increase in perfusion in the lung receiving <10 Gy. Conclusion: Hypo-fractionated stereotactic RT appears to cause a dose-dependent reduction in regional lung perfusion. There appears to be a threshold effect with no apparent perfusion loss at doses <10 Gy, though this might be in part due to the normalization technique used. Additional data is needed from a larger number of patients to better assess this issue. This sort of data can be used to assist optimizing RT treatment plans that minimize the risk of lung injury. Partly supported by the NIH (CA69579) and the Lance Armstrong

  1. Clinical Outcome of Patients Transplanted with Marginal Donor Lungs via Ex Vivo Lung Perfusion Compared to Standard Lung Transplantation.

    PubMed

    Fildes, James E; Archer, Louise D; Blaikley, John; Ball, Alexandra L; Stone, John P; Sjöberg, Trygve; Steen, Stig; Yonan, Nizar

    2015-05-01

    Lung transplantation is limited by a scarcity of suitable donors resulting in high waiting list mortality. Ex vivo lung perfusion (EVLP) allows the evaluation and reconditioning of marginal donor lungs for use in transplantation. This study aimed to compare clinical outcome of patients transplanted with marginal organs by means of EVLP with a standard lung transplant cohort through a multicenter open trial. Group 1 (n = 9) included patients transplanted using EVLP reconditioned marginal lungs. Group 2 (n = 46) consisted of date-matched patients transplanted using standard transplantation of acceptable lungs. The primary composite endpoint included acute rejection and infection at 12 months after transplantation. There was no significant difference in the overall incidence of acute rejection (P = 0.754) and the number of treated infection episodes (proven/probable pneumonia; P = 0.857/0.368 and proven/probable tracheobronchitis; P = 0.226/0.529) up to 12 months after transplantation, between group 1 and group 2. Additionally, there was no significant difference in early clinical outcome, including intensive care unit stay, hospital stay, and 1 year mortality between the two groups (P = 0.338, P = 0.112 and P = 0.372, respectively). This multicenter study demonstrates that EVLP is associated with no adverse effect on clinical outcome, including the incidence of acute rejection and infection after lung transplantation.

  2. An observational study of Donor Ex Vivo Lung Perfusion in UK lung transplantation: DEVELOP-UK.

    PubMed Central

    Fisher, Andrew; Andreasson, Anders; Chrysos, Alexandros; Lally, Joanne; Mamasoula, Chrysovalanto; Exley, Catherine; Wilkinson, Jennifer; Qian, Jessica; Watson, Gillian; Lewington, Oli; Chadwick, Thomas; McColl, Elaine; Pearce, Mark; Mann, Kay; McMeekin, Nicola; Vale, Luke; Tsui, Steven; Yonan, Nizar; Simon, Andre; Marczin, Nandor; Mascaro, Jorge; Dark, John

    2016-01-01

    BACKGROUND Many patients awaiting lung transplantation die before a donor organ becomes available. Ex vivo lung perfusion (EVLP) allows initially unusable donor lungs to be assessed and reconditioned for clinical use. OBJECTIVE The objective of the Donor Ex Vivo Lung Perfusion in UK lung transplantation study was to evaluate the clinical effectiveness and cost-effectiveness of EVLP in increasing UK lung transplant activity. DESIGN A multicentre, unblinded, non-randomised, non-inferiority observational study to compare transplant outcomes between EVLP-assessed and standard donor lungs. SETTING Multicentre study involving all five UK officially designated NHS adult lung transplant centres. PARTICIPANTS Patients aged ≥ 18 years with advanced lung disease accepted onto the lung transplant waiting list. INTERVENTION The study intervention was EVLP assessment of donor lungs before determining suitability for transplantation. MAIN OUTCOME MEASURES The primary outcome measure was survival during the first 12 months following lung transplantation. Secondary outcome measures were patient-centred outcomes that are influenced by the effectiveness of lung transplantation and that contribute to the health-care costs. RESULTS Lungs from 53 donors unsuitable for standard transplant were assessed with EVLP, of which 18 (34%) were subsequently transplanted. A total of 184 participants received standard donor lungs. Owing to the early closure of the study, a non-inferiority analysis was not conducted. The Kaplan-Meier estimate of survival at 12 months was 0.67 [95% confidence interval (CI) 0.40 to 0.83] for the EVLP arm and 0.80 (95% CI 0.74 to 0.85) for the standard arm. The hazard ratio for overall 12-month survival in the EVLP arm relative to the standard arm was 1.96 (95% CI 0.83 to 4.67). Patients in the EVLP arm required ventilation for a longer period and stayed longer in an intensive therapy unit (ITU) than patients in the standard arm, but duration of overall hospital

  3. Quantification of lung injury using ventilation and perfusion distributions obtained from gamma scintigraphy.

    PubMed

    Brook, B S; Murphy, C M; Breen, D; Miles, A W; Tilley, D G; Wilson, A J

    2007-12-01

    This paper explores the potential of isotope V/Q lung scans to quantify lung disease. Areas of restricted perfusion in subjects with a pulmonary embolus (PE) were identified in 3D reconstructions of V/Q images achieved using anatomical data from the Visible Human Project. From these, the extent of lung damage was quantified. Significant differences in the values of both LogSD V and LogSD Q (p > 0.05) obtained from plots of V and Q against Log(V/Q) were found between normal subjects and subjects with a PE, but no correlation was found between either of these parameters and the degree of lung damage in subjects with a PE (p > 0.05). Whilst V/Q values were log normally distributed, the V/Q distributions from the subjects with a PE failed to show the bimodal distribution predicted from theoretical considerations and MIGET measurements previously reported. There was a statistically significant difference in the mean and standard deviation values of the V/Q distributions between normal subject and subjects with a PE (p < 0.05) but not in the median values (p > 0.05). There was no correlation between the mean, median and standard deviation of the distributions from the subjects with a PE and the percentage of damage present (p > 0.05).

  4. Method of Isolated Ex Vivo Lung Perfusion in a Rat Model: Lessons Learned from Developing a Rat EVLP Program

    PubMed Central

    Nelson, Kevin; Bobba, Christopher; Eren, Emre; Spata, Tyler; Tadres, Malak; Hayes,, Don; Black, Sylvester M.

    2015-01-01

    The number of acceptable donor lungs available for lung transplantation is severely limited due to poor quality. Ex-Vivo Lung Perfusion (EVLP) has allowed lung transplantation in humans to become more readily available by enabling the ability to assess organs and expand the donor pool. As this technology expands and improves, the ability to potentially evaluate and improve the quality of substandard lungs prior to transplant is a critical need. In order to more rigorously evaluate these approaches, a reproducible animal model needs to be established that would allow for testing of improved techniques and management of the donated lungs as well as to the lung-transplant recipient. In addition, an EVLP animal model of associated pathologies, e.g., ventilation induced lung injury (VILI), would provide a novel method to evaluate treatments for these pathologies. Here, we describe the development of a rat EVLP lung program and refinements to this method that allow for a reproducible model for future expansion. We also describe the application of this EVLP system to model VILI in rat lungs. The goal is to provide the research community with key information and “pearls of wisdom”/techniques that arose from trial and error and are critical to establishing an EVLP system that is robust and reproducible. PMID:25741794

  5. Quantification of nonuniform distribution of hemi-lung perfusion in chronic obstructive pulmonary disease.

    PubMed

    Mitomo, Osamu

    2016-01-01

    Nonuniform distribution (NUD) of perfusion on single photon emission computed tomography (SPECT) is caused by impaired perfusion-related fluctuations of the functional volume (FFV). It was determined if digital analysis of NUD in each hemi-lung damaged by chronic obstructive pulmonary disease (COPD) could improve the whole lung impairment assessment. We examined 665 subjects and 8 controls by SPECT. The basic whole lung SPECT volume was defined at 10% of maximum whole lung count cutoff threshold (T h). For the whole lung and each hemi-lung, the 10% T h width volume, FFV rate, and misfit from the control were calculated at every T h width number (n) from 1 to 9 for every additional 10% T h from 10 to 100%. The misfit value integrated from 1 to 9 of n was defined by 3 NUD indices: D, whole lung NUD index; D rl , the index for the sum of each hemi-lung NUD; and D (I) , the NUD index with every interpolating pattern in which FFV rates of hemi-lungs comprised negative and positive value at the same n. D rl index was the sum of D and D (I) indices in all patients. D rl and D indices significantly increased in pulmonary disease subjects relative to those of the normal group and non-pulmonary disease subjects. D rl and D indices increased in COPD subjects. Progressive COPD subjects had larger D rl index values and "diffuse and even" hemi-lung impairment. The three indices quantizing FFV itself leading to NUD helped to digitally evaluate the degree of lung impairment of perfusion. Clinically, it is expected that the NUD indices and images obtained by SPECT, which visually and digitally show the pathological fluctuations in perfusion caused by lung impairment, will be able to provide specific and useful information for improving treatment and/or care of subjects with COPD.

  6. Lung scan perfusion defects limited to matching pleural effusions: low probability of pulmonary embolism

    SciTech Connect

    Bedont, R.A.; Datz, F.L.

    1985-12-01

    Patients with a new pleural effusion are often sent for a ventilation-perfusion scan to exclude a pulmonary embolism. This retrospective study assessed the probability of pulmonary embolism when a pleural effusion and a perfusion defect of similar size are the only significant imaging abnormalities. In 451 reports of patients who were scanned for suspected pulmonary embolism, 53 had perfusion defects secondary to pleural effusion without other significant perfusion defects. Using pulmonary angiography, venography, analysis of pleural fluid, clinical course, and other radiographic and laboratory studies to establish the final diagnosis, only two patients had documented venous thrombotic disease: one had pulmonary emboli, the other thrombophlebitis. Lung scans having significant perfusion defects limited to pleural effusions and matching them in size have a low probability for pulmonary embolism.

  7. Ga-68 MAA Perfusion 4D-PET/CT Scanning Allows for Functional Lung Avoidance Using Conformal Radiation Therapy Planning.

    PubMed

    Siva, Shankar; Devereux, Thomas; Ball, David L; MacManus, Michael P; Hardcastle, Nicholas; Kron, Tomas; Bressel, Mathias; Foroudi, Farshad; Plumridge, Nikki; Steinfort, Daniel; Shaw, Mark; Callahan, Jason; Hicks, Rodney J; Hofman, Michael S

    2016-02-01

    Ga-68-macroaggregated albumin ((68)Ga-perfusion) positron emission tomography/computed tomography (PET/CT) is a novel imaging technique for the assessment of functional lung volumes. The purpose of this study was to use this imaging technique for functional adaptation of definitive radiotherapy plans in patients with non-small cell lung cancer (NSCLC). This was a prospective clinical trial of patients with NSCLC who received definitive 3-dimensional (3D) conformal radiotherapy to 60 Gy in 30 fx and underwent pretreatment respiratory-gated (4-dimensional [4D]) perfusion PET/CT. The "perfused" lung volume was defined as all lung parenchyma taking up radiotracer, and the "well-perfused" lung volume was contoured using a visually adapted threshold of 30% maximum standardized uptake value (SUV max). Alternate 3D conformal plans were subsequently created and optimized to avoid perfused and well-perfused lung volumes. Functional dose volumetrics were compared using mean lung dose (MLD), V5 (volume receiving 5 Gy or more), V10, V20, V30, V40, V50, and V60 parameters. Fourteen consecutive patients had alternate radiotherapy plans created based on functional lung volumes. When considering the original treatment plan, the dose to perfused and well-perfused functional lung volumes was similar to that of the conventional anatomical lung volumes with an average MLD of 12.15, 12.67, and 12.11 Gy, respectively. Plans optimized for well-perfused lung improved functional V30, V40, V50, and V60 metrics (all P values <.05). The functional MLD of well-perfused lung was improved by a median of 0.86 Gy, P < .01. However, plans optimized for perfused lung only showed significant improvement in the functional V60 dose parameter (median 1.00%, P = .04) but at a detriment of a worse functional V5 (median 3.33%, P = .05). This study demonstrates proof of principle that 4D-perfusion PET/CT may enable functional lung avoidance during treatment planning of patients with NSCLC. Radiotherapy plans

  8. Effect of carbon monoxide on xenobiotic metabolism in the isolated perfused rabbit lung

    SciTech Connect

    Trela, B.A.

    1988-01-01

    It was the aim of this study to determine the level and duration of CO exposure necessary to alter mixed function oxidase-mediated activity in the intact lung and to determine the magnitude of this effect. The effect of CO on the mixed function oxidase-mediated activities of aminopyrine, aniline, 4-ipomeanol and p-nitroanisole in isolated perfused rabbit lungs (IPRL) was investigated. Several concentrations of CO were evaluated for their effect on cytochrome P-450-mediated activity in the lung. Both artificial medium and whole blood were utilized as recirculating perfusates. Monomethyl-4-aminoantipyrine was the major metabolite of aminopyrine produced by in vitro hepatic and pulmonary preparations and by the intact lung. Ventilation of isolated rabbit lungs with 7.5% CO for 2.5 hours caused a 40% decrease in the rates of metabolism of both aminopyrine and p-nitroanisole. This level of CO exposure did not alter the cytochrome P-450-mediated metabolism of aniline nor 4-ipomeanol in the intact lung. Aminopyrine metabolism in isolated rabbit lungs perfused with whole blood was also decreased following the administration of 7.5% CO suggesting that the hemoglobin in whole blood affords no protection against CO-induced inhibition of mixed function oxidase activity in the intact lung. The isozyme of cytochrome P-450 which preferentially metabolizes aminopyrine and p-nitroanisole may be more sensitive to CO-induced inhibition than the form(s) which metabolize aniline and 4-ipomeanol.

  9. Automatic delineation of functional lung volumes with (68)Ga-ventilation/perfusion PET/CT.

    PubMed

    Le Roux, Pierre-Yves; Siva, Shankar; Callahan, Jason; Claudic, Yannis; Bourhis, David; Steinfort, Daniel P; Hicks, Rodney J; Hofman, Michael S

    2017-10-10

    Functional volumes computed from (68)Ga-ventilation/perfusion (V/Q) PET/CT, which we have shown to correlate with pulmonary function test parameters (PFTs), have potential diagnostic utility in a variety of clinical applications, including radiotherapy planning. An automatic segmentation method would facilitate delineation of such volumes. The aim of this study was to develop an automated threshold-based approach to delineate functional volumes that best correlates with manual delineation. Thirty lung cancer patients undergoing both V/Q PET/CT and PFTs were analyzed. Images were acquired following inhalation of Galligas and, subsequently, intravenous administration of (68)Ga-macroaggreted-albumin (MAA). Using visually defined manual contours as the reference standard, various cutoff values, expressed as a percentage of the maximal pixel value, were applied. The average volume difference and Dice similarity coefficient (DSC) were calculated, measuring the similarity of the automatic segmentation and the reference standard. Pearson's correlation was also calculated to compare automated volumes with manual volumes, and automated volumes optimized to PFT indices. For ventilation volumes, mean volume difference was lowest (- 0.4%) using a 15%max threshold with Pearson's coefficient of 0.71. Applying this cutoff, median DSC was 0.93 (0.87-0.95). Nevertheless, limits of agreement in volume differences were large (- 31.0 and 30.2%) with differences ranging from - 40.4 to + 33.0%. For perfusion volumes, mean volume difference was lowest and Pearson's coefficient was highest using a 15%max threshold (3.3% and 0.81, respectively). Applying this cutoff, median DSC was 0.93 (0.88-0.93). Nevertheless, limits of agreement were again large (- 21.1 and 27.8%) with volume differences ranging from - 18.6 to + 35.5%. Using the 15%max threshold, moderate correlation was demonstrated with FEV1/FVC (r = 0.48 and r = 0.46 for ventilation and perfusion images

  10. Differential role of actin in lung endothelial and epithelial barrier properties in perfused rabbit lungs.

    PubMed

    Ermert, L; Rössig, R; Hansen, T; Schütte, H; Aktories, K; Seeger, W

    1996-01-01

    Lung fluid balance is critically dependent on capillary endothelial and alveolar epithelial barrier properties, and cytoskeletal components have been implicated in these barrier functions. In an earlier study, we perfused Clostridium botulinum C2 toxin, which effects selective loss of non-muscle F-actin, through isolated rabbit lungs: a severalfold increase in the capillary filtration coefficient (Kfc) was noted, together with attenuations and disruptions of endothelial cells upon electron microscopic examination. In this model we have investigated the influence of the C2 toxin on alveolar epithelial barrier properties. Epithelial permeability was assessed by continuous monitoring of the transepithelial passage of technetium-labelled diethylenetriamine penta-acetic acid (99mTc-DTPA), offered to the alveolar surface by aerosol technique. Intravascular administration of hydrogen peroxide, used as control agent, was shown to provoke a four- to fivefold increase in the clearance rate of 99mTc-DTPA under conditions of severe fluid leakage into the lung interstitial and alveolar space. Intravascular administration of C2 toxin caused a dose- and time-dependent increase in Kfc values (8-15 fold), but the Tc-DTPA clearance rate was entirely unaffected. Moreover, transbronchial application of C2 toxin again reproduced the manifold increase in Kfc data (about six fold), but the rate of transepithelial passage of the hydrophilic Tc-DTPA complex remained unchanged. We conclude that the barrier properties of the lung microvascular endothelial and epithelial layer are differentially regulated. It is suggested that the actin microfilament system plays a decisive role in the structural and functional integrity of the endothelial but not the epithelial barrier.

  11. Evaluation of postoperative lung volume and perfusion changes by dual-energy computed tomography in patients with lung cancer.

    PubMed

    Choe, Jooae; Lee, Sang Min; Chae, Eun Jin; Lee, Sang Min; Kim, Yong-Hee; Kim, Namkug; Seo, Joon Beom

    2017-05-01

    The aim of our study was to retrospectively evaluate postoperative physiologic changes in lung cancer patients using dual-energy CT (DECT), and develop modified methods reflecting postoperative change for predicting pulmonary function. 88 patients (M:F=64:24; mean age, 63.5 years) with lung cancer who underwent DECT and pulmonary function tests before and after operation were included. Volume and iodine values for perfusion of each lobe were quantified. The predicted postoperative FEV1 using the current method was calculated by multiplying the preoperative FEV1 by the fractional contribution of perfusion of the remaining lung. The modified method reflecting postoperative volume change was compared to the current method. Postoperative lung volume showed compensatory increases in the contralateral and remaining ipsilateral lobes, with a significantly greater increase in the ipsilateral lobe than contralateral lobe (21.8%±46.2% vs. 10.0%±20.8%, P=0.031). Perfusion analysis showed blood volume increases in both ipsilateral and contralateral lobes without statistical differences (blood volume ratio difference, 29.2%±26.7 vs. 24.6%±16.5, P=0.368). The performance of the modified method considering postoperative lung volume change was comparable to that of the current method in the development and validation datasets (95% CI, -24.5% to 37.1% vs. -33.3% to 22.2% and -23.6% to 32.0% vs. -31.9% to 16.0%, respectively). Postoperative compensatory increases in lung volume and perfusion occur in different ways. Our modified method incorporating postoperative lung volume changes can be considered a comparable method for prediction of postoperative lung function. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Distribution of lung blood on modified bilateral Glenn shunt evaluated by Tc-99m-MAA lung perfusion scintigraphy: A retrospective study.

    PubMed

    Si, Biao; Luan, Zhao-Sheng; Wang, Tong-Jian; Ning, Yan-Song; Li, Na; Zhu, Meng; Liu, Zhong-Min; Ding, Guang-Hong; Qiao, Bin

    2016-09-01

    The aim of the present study was to determine the distribution of lung blood in a modified bilateral Glenn procedure designed in our institute with lung perfusion scintigraphy. Sixteen consecutive patients who underwent modified bilateral Glenn operation from 2011 to 2014 were enrolled in the study. The control group consisted of 7 patients who underwent bidirectional Glenn shunt. Radionuclide lung perfusion scintigraphy was performed using Tc-99m-macro aggregated albumin (MAA) in all patients. For the patients in modified bilateral Glenn group, the time at which the radioactivity accumulation peaked did not differ significantly between the right and left lung field (t = 0.608, P = 0.554). The incidence of perfusion abnormality in each lung lobe also did not differ significantly (P = 0.426 by Fisher exact test). The radioactive counts were higher in the right lung than in the left lung, but the difference was not statistically significant (t = 1.502, P = 0.157). Radioactive perfusion in the lower lung field was significantly greater than that in the upper field (t = 4.368, P < 0.001). Compared with that in the bidirectional Glenn group, the ratio of radioactivity in the right lung to that in left lung was significantly lower in the modified bilateral Glenn group (t = 3.686, P = 0.002). Lung perfusion scintigraphy confirmed the benefit of the modified bilateral Glenn shunt with regard to more balanced blood perfusion in both lungs.

  13. [A complete ventilation-perfusion mismatch following one-sided lung transplantation and postoperative hemothorax].

    PubMed

    Jellinek, H; Klepetko, W; Hiesmayr, M

    1992-03-01

    Eight days after single-lung transplantation for pulmonary hypertension, a patient presented with a hemothorax on the side of the transplanted lung that required acute thoracotomy. Pulmonary artery pressure had decreased from 78/32/58 mmHg prior to the transplant to 42/18/27 mmHg on the 2nd postoperative day. Therefore, a predominance of perfusion to the transplanted lung was expected. During induction of anesthesia, in spite of ventilation with pure oxygen the patient developed a hypoxic cardiac arrest (paO2 26 mmHg, 40% saturation measured by pulse oximetry) requiring external chest compression. Auscultation and chest movements suggested that the transplanted lung was not ventilated. Because blood flow went mainly to the transplanted lung, ventilation of the native lung was almost totally dead-space ventilation. To enable ventilation of the compressed transplanted lung, the patient was intubated using a single-lumen bronchial blocker tube to block the mainstem bronchus of the native lung. The transplanted lung could then be ventilated. Saturation increased and epinephrine re-established a stable circulation; 2500 ml blood were removed from the pleura without further complications. On the 7th postoperative day the patient was discharged from the intensive care unit without neurological deficits. A perfusion scan 28 days post-transplant revealed 89% of the perfusion going to the transplanted lung. Atelectasis of this lung resulted in a large intrapulmonary right-to-left shunt. Hypoxic pulmonary vasoconstriction could not ameliorate the shunt because of the high pulmonary vascular resistance of the native lung.(ABSTRACT TRUNCATED AT 250 WORDS)

  14. Natural course of treated pulmonary embolism. Evaluation by perfusion lung scintigraphy, gas exchange, and chest roentgenogram.

    PubMed

    Prediletto, R; Paoletti, P; Fornai, E; Perissinotto, A; Petruzzelli, S; Formichi, B; Ruschi, S; Palla, A; Giannella-Neto, A; Giuntini, C

    1990-03-01

    Perfusion lung scintigrams, pulmonary gas exchange data, and chest roentgenograms were obtained in 33 patients during acute embolism and over the following six months in order to assess their clinical usefulness in monitoring the effect of therapy. To this purpose, the measurement of pulmonary gas exchange and the presence of chest x-ray findings were compared with perfusion lung scintigraphic abnormalities both at diagnosis and after 7, 30, and 180 days during treatment. More than 50 percent of the pulmonary arterial tree was obstructed at diagnosis, and a large part of perfusion recovery was complete within the first month. All of the gas exchange parameters were abnormal at diagnosis, and the rate of their improvement was related to that of perfusion recovery. Interestingly, PaO2st (ie, PaO2 corrected for hyperventilation) and VE tended to return to normal during the first month as a consequence of the progressive recovery of perfusion, whereas oxygen and carbon dioxide gradients and physiologic dead space showed the persistence of some abnormalities six months after diagnosis. Significant correlations were observed between the number of ULSs evaluated on the perfusion lung scintigram (and considered an index of the severity of pulmonary embolization) and all of the gas exchange parameters at diagnosis (correlation coefficients averaged from 0.41 to 0.73) and after 7 and 30 days. The enlargement of the right descending pulmonary artery and particularly the "sausage" sign and the Westermark sign were significantly associated with a higher degree of gas exchange impairment and with a more severe embolization. In conclusion, this study demonstrates that perfusion lung scintigraphy has a primary role in monitoring the recovery of patients with pulmonary embolism under treatment. Moreover, the chest roentgenogram may help in this purpose. A second major result is that the simple measurement of some gas exchange parameters may allow the assessment of functional

  15. Isolated Lung Perfusion as an Adjuvant Treatment of Colorectal Cancer Lung Metastases: A Preclinical Study in a Pig Model

    PubMed Central

    Pagès, Pierre-Benoit; Facy, Olivier; Mordant, Pierre; Ladoire, Sylvain; Magnin, Guy; Lokiec, Francois; Ghiringhelli, Francois; Bernard, Alain

    2013-01-01

    Background The lung is a frequent site of colorectal cancer (CRC) metastases. After surgical resection, lung metastases recurrences have been related to the presence of micrometastases, potentially accessible to a high dose chemotherapy administered via adjuvant isolated lung perfusion (ILP). We sought to determine in vitro the most efficient drug when administered to CRC cell lines during a short exposure and in vivo its immediate and delayed tolerance when administered via ILP. Methods First, efficacy of various cytotoxic molecules against a panel of human CRC cell lines was tested in vitro using cytotoxic assay after a 30-minute exposure. Then, early (operative) and delayed (1 month) tolerance of two concentrations of the molecule administered via ILP was tested on 19 adult pigs using hemodynamic, biological and histological criteria. Results In vitro, gemcitabine (GEM) was the most efficient drug against selected CRC cell lines. In vivo, GEM was administered via ILP at regular (20 µg/ml) or high (100 µg/ml) concentrations. GEM administration was associated with transient and dose-dependant pulmonary vasoconstriction, leading to a voluntary decrease in pump inflow in order to maintain a stable pulmonary artery pressure. After this modulation, ILP using GEM was not associated with any systemic leak, systemic damage, and acute or delayed histological pulmonary toxicity. Pharmacokinetics studies revealed dose-dependant uptake associated with heterogenous distribution of the molecule into the lung parenchyma, and persistent cytotoxicity of venous effluent. Conclusions GEM is effective against CRC cells even after a short exposure. ILP with GEM is a safe and reproducible technique. PMID:23527205

  16. Comparison of Celsior and Perfadex lung preservation solutions in rat lungs subjected to 6 and 12 hours of ischemia using an ex-vivo lung perfusion system.

    PubMed

    Menezes, Arteiro Queiroz; Pêgo-Fernandes, Paulo Manuel; Cardoso, Paulo Francisco Guerreiro; Braga, Karina Andrighetti de Oliveira; Nepomuceno, Natalia Aparecida; Pazetti, Rogerio; Correia, Aristides Tadeu; Canzian, Mauro; Santim, Jacqueline Klarosk; Jatene, Fabio Biscegli

    2012-11-01

    This study evaluated the performance of lungs that were preserved with different solutions (Celsior, Perfadex or saline) in an ex vivo rat lung perfusion system. Sixty Wistar rats were anesthetized, anticoagulated and randomized into three groups (n = 20). The rats were subjected to antegrade perfusion via the pulmonary artery with Perfadex, Celsior, or saline, followed by 6 or 12 hours of ischemia (4ºC, n = 10 in each group). Respiratory mechanics, gas exchange and hemodynamics were measured at 10-minute intervals during the reperfusion of heart-lung blocks in an ex vivo system (IL2-Isolated Perfused Rat or Guinea Pig Lung System, Harvard Apparatus, Holliston, Massachusetts, USA; Hugo Sachs Elektronik, Germany) for 60 minutes. The lungs were prepared for histopathology and evaluated for edema following reperfusion. Group comparisons were performed using ANOVA and the Kruskal-Wallis test with a 5% level of significance. Gas exchange was not significantly different between lungs perfused with either Perfadex or Celsior at the same ischemic times, but it was very low in lungs that were preserved with saline. Airway resistance was greater in the lungs that were preserved for 12 hours. Celsior lungs that were preserved for 6 and 12 hours exhibited lower airway resistance (p = 0.01) compared to Perfadex lungs. Pulmonary artery pressure was not different between the groups, and no significant differences in histopathology and apoptosis were observed between the groups. Lungs that were preserved with Celsior or Perfadex exhibited similar gas exchange and histopathological findings. Airway resistance was slightly lower in the Celsior-preserved lungs compared with the Perfadex-preserved lungs.

  17. Ventilation-perfusion scintigraphy in an adult with congenital unilateral hyperlucent lung

    SciTech Connect

    Wegener, W.A.; Velchik, M.G. )

    1990-10-01

    A variety of congenital and acquired etiologies can give rise to the radiographic finding of a unilateral hyperlucent lung. An unusual case of congenital lobar emphysema diagnosed in a young adult following the initial discovery of a hyperexpanded, hyperlucent lung is reported. Although subsequent bronchoscopy and radiologic studies detailed extensive anatomic abnormalities, functional imaging also played an important role in arriving at this rare diagnosis. In particular, ventilation-perfusion scintigraphy identified the small contralateral lung as the functional lung and helped narrow the differential diagnosis to etiologies involving obstructive airway disorders.

  18. Effect of Fenoterol on PAF-induced lung edema in isolated and perfused rabbit lungs.

    PubMed

    Pesce, L; Tristano, S; Friedman, E; Comellas, A; Marcano, H; Sanchez de León, R

    1998-11-01

    We have studied the effects of fenoterol on PAF-induced response in pulmonary circulation. We used 28 isolated and perfused rabbit lungs preparations: eight control preparations (CP), four vehicles preparations (VP), eight PAF preparations (PP) with two doses of PAF, one called low dose (LD = 0.5 microg/kg of weight) and the other high dose (HD = 1 microg/kg of weight) and eight Fenoterol preparations (FP) which we administered 0.05 mg of Fenoterol for 15 min, followed by a LD and HD of PAF. FP prevented elevation of pulmonary artery pressure (Ppa) as compared to PP, at LD of PAF: 12.615 (CI 95%: 8.57-20.885) versus 83.705 (CI 95%: 50.55-114.3) cm of water; and at HD of PAF: 19.38 (CI 95%: 11.235-28.94) versus 205.1 (CI 95%: 141.3-271) cm of water respectively. FP prevented the increase in fluid filtration rate (FFR) observed in PP at both doses of PAF LD: 0.765 (CI 95%: 0.07-3.385) versus 0.01 (CI 95%: -0.05-0.005) g/min; HD: 5.515 (CI 95%: 2.425-8.865) versus 0.03 (CI 95%: 0-0.33) g/min. Our results suggest that PAF has a vasoconstrictor effect that produces lung edema and this effect is inhibited by fenoterol.

  19. Automated lung outline reconstruction in ventilation-perfusion scans using principal component analysis techniques.

    PubMed

    Serpen, G; Iyer, R; Elsamaloty, H M; Parsai, E I

    2003-03-01

    The present work addresses the development of an automated software-based system utilized in order to create an outline reconstruction of lung images from ventilation-perfusion scans for the purpose of diagnosing pulmonary embolism. The proposed diagnostic software procedure would require a standard set of digitized ventilation-perfusion scans in addition to correlated chest X-rays as key components in the identification of an ideal template match used to approximate and reconstruct the outline of the lungs. These reconstructed lung images would then be used to extract the necessary PIOPED-compliant features which would warrant a pulmonary embolism diagnosis. In order to evaluate this issue, two separate principal component analysis (PCA) algorithms were employed independently, including Eigenlungs, which was adapted from the Eigenfaces method, and an artificial neural network. The results obtained through MATLAB(TM) simulation indicated that lung outline reconstruction through the PCA approach carries significant viability.

  20. The First Experience of Ex-Vivo Lung Perfusion (EVLP) in Iran: An Effective Method to Increase Suitable Lung for Transplantation

    PubMed Central

    Shafaghi, S.; Najafizadeh, K.; Sheikhy, K.; Ansari Aval, Z.; Farzanegan, B.; Mafhoomi, Y.; Faghih Abdollahi, Z.; Emami, H.; Mortaz, E.; Porabdollah, M.; Jahangiri Fard, A.; Nikobayan Safaei, M.; Slama, A.; Aigner, C.; Hosseini-Baharanchi, F. S.; Abbasi Dezfuli, A.

    2016-01-01

    Background: Although lung transplantation is a well-accepted treatment for end-stage lung diseases patients, only 15%–20% of the brain-dead donors’ lungs are usable for transplantation. This results in high mortality of candidates on waiting lists. Ex-vivo lung perfusion (EVLP) is a novel method for better evaluation of a potential lung for transplantation. Objective: To report the first experience of EVLP in Iran. Methods: The study included a pig in Vienna Medical University, Vienna, Austria, and 4 humans in Masih Daneshvari Hospital, Tehran, Iran. All brain-dead donors from 2013 to 2015 in Tehran were evaluated for EVLP. Donors without signs of severe chest trauma or pneumonia, with poor oxygenation were included. Results: An increasing trend in difference between the pulmonary arterial pO2 and left atrial pO2, an increasing pattern in dynamic lung compliance, and a decreasing trend in the pulmonary vascular resistance, were observed. Conclusion: The initial experience of EVLP in Iran was successful in terms of important/critical parameters. The results emphasize on some important considerations such as precisely following standard lung harvesting and monitoring temperature and pressure. EVLP technique may not be a cost-effective option for low-income countries at first glance. However, because this is the only therapeutic treatment for end-stage lung disease, it is advisable to continue working on this method to find alternatives with lesser costs. PMID:28078061

  1. Potential targets for lung squamous cell carcinoma

    Cancer.gov

    Researchers have identified potential therapeutic targets in lung squamous cell carcinoma, the second most common form of lung cancer. The Cancer Genome Atlas (TCGA) Research Network study comprehensively characterized the lung squamous cell carcinoma gen

  2. Teaching Ventilation/Perfusion Relationships in the Lung

    ERIC Educational Resources Information Center

    Glenny, Robb W.

    2008-01-01

    This brief review is meant to serve as a refresher for faculty teaching respiratory physiology to medical students. The concepts of ventilation and perfusion matching are some of the most challenging ideas to learn and teach. Some strategies to consider in teaching these concepts are, first, to build from simple to more complex by starting with a…

  3. Teaching Ventilation/Perfusion Relationships in the Lung

    ERIC Educational Resources Information Center

    Glenny, Robb W.

    2008-01-01

    This brief review is meant to serve as a refresher for faculty teaching respiratory physiology to medical students. The concepts of ventilation and perfusion matching are some of the most challenging ideas to learn and teach. Some strategies to consider in teaching these concepts are, first, to build from simple to more complex by starting with a…

  4. Accuracy and feasibility of dynamic contrast-enhanced 3D MR imaging in the assessment of lung perfusion: comparison with Tc-99 MAA perfusion scintigraphy.

    PubMed

    Yilmaz, E; Akkoclu, A; Degirmenci, B; Cooper, R A; Sengun, B; Gulcu, A; Osma, E; Ucan, E S

    2005-08-01

    The aim of this study was to correlate findings of perfusion magnetic resonance imaging (MRI) and perfusion scintigraphy in cases where there was a suspicion of abnormal pulmonary vasculature, and to evaluate the usefulness of MRI in the detection of perfusion deficits of the lung. In all, 17 patients with suspected abnormality of the pulmonary vasculature underwent dynamic contrast-enhanced MRI. T1-weighted 3D fast-field echo pulse sequences were obtained (TR/TE 3.3/1.58 ms; flip angle 30 degrees; slice thickness 12 to 15 mm). The dynamic study was acquired in the coronal plane following administration of 0.1 mmol/kg gadopentetate dimeglumine. A total of 8 to 10 sections repeated 20 to 25 times at intervals of 1s were performed. Perfusion lung scintigraphy was carried out a maximum of 48 h before the MR examination in all cases. Two radiologists, who were blinded to the clinical data and results of other imaging methods, reviewed all coronal sections. MR perfusion images were independently assessed in terms of segmental or lobar perfusion defects in the 85 lobes of the 17 individuals, and the findings were compared with the results of scintigraphy. Of the 17 patients, 8 were found to have pulmonary emboli, 2 chronic obstructive pulmonary disease with emphysema, 2 bullous emphysema, 2 Takayasu arteritis and 1 had a hypoplastic pulmonary artery. Pulmonary perfusion was completely normal in 2 cases. In 35 lobes, perfusion defects were detected using both methods, in 4 with MR alone and in 9 only with scintigraphy. There was good agreement between MRI and scintigraphy findings (kappa=0.695). Pulmonary perfusion MRI is a new alternative to scintigraphy in the evaluation of pulmonary perfusion for various lung disorders. In addition, this technique allows measurement and quantification of pulmonary perfusion abnormalities.

  5. Successful Transplantation of Lungs From an Uncontrolled Donor After Circulatory Death Preserved In Situ by Alveolar Recruitment Maneuvers and Assessed by Ex Vivo Lung Perfusion.

    PubMed

    Valenza, F; Citerio, G; Palleschi, A; Vargiolu, A; Fakhr, B Safaee; Confalonieri, A; Nosotti, M; Gatti, S; Ravasi, S; Vesconi, S; Pesenti, A; Blasi, F; Santambrogio, L; Gattinoni, L

    2016-04-01

    We developed a protocol to procure lungs from uncontrolled donors after circulatory determination of death (NCT02061462). Subjects with cardiovascular collapse, treated on scene by a resuscitation team and transferred to the emergency room, are considered potential donors once declared dead. Exclusion criteria include unwitnessed collapse, no-flow period of >15 min and low flow >60 min. After death, lung preservation with recruitment maneuvers, continuous positive airway pressure, and protective mechanical ventilation is applied to the donor. After procurement, ex vivo lung perfusion (EVLP) is performed. From November 2014, 10 subjects were considered potential donors; one of these underwent the full process of procurement, EVLP, and transplantation. The donor was a 46-year-old male who died because of thoracic aortic dissection. Lungs were procured 4 h and 48 min after death, and deemed suitable for transplantation after EVLP. Lungs were then offered to a rapidly deteriorating recipient with cystic fibrosis (lung allocation score [LAS] 46) who consented to the transplant in this experimental setting. Six months after transplantation, the recipient is in good condition (forced expiratory volume in 1 s 85%) with no signs of rejection. This protocol allowed procurement of lungs from an uncontrolled donor after circulatory determination of death following an extended period of warm ischemia. © 2015 The Authors. American Journal of Transplantation published by Wiley Periodicals, Inc. on behalf of American Society of Transplant Surgeons.

  6. Advances in machine perfusion graft viability assessment in kidney, liver, pancreas, lung, and heart transplant.

    PubMed

    Balfoussia, Danai; Yerrakalva, Dharani; Hamaoui, Karim; Papalois, Vassilios

    2012-04-01

    Solid organ transplant constitutes the definitive treatment for end-stage organ failure. Better organ preservation methods have enabled use of marginal grafts, thereby expanding the donor pool to meet the growing demand for organs. Static cold storage as a preservation method has been superseded largely by machine perfusion in kidney transplant, with work regarding its use in other organ transplants ongoing. We hope that machine perfusion will allow better graft preservation, and pretransplant assessment, and optimization. The most extensive laboratory, preclinical, and clinical research into machine perfusion organ preservation has focused on kidneys. Successful outcomes in its use in renal transplant have sparked interest for its development and application to the liver, pancreas, heart, and lungs. This article reviews the current state of machine perfusion in abdominal and thoracic organ transplant, focusing on the recent developments in assessing graft viability.

  7. Lung mass appearing as a dilated left ventricle on Tc-99m tetrofosmin myocardial perfusion scintigraphy.

    PubMed

    Gnanasegaran, Gopinath; Williams, Robert; Mclean, Emma; O' Connell, Rachel; Nunan, Thomas O; O'Doherty, Michael J

    2009-09-01

    Tc-99m tetrofosmin is a common tracer used in myocardial perfusion scintigraphy. Several benign and malignant tumors also take up tetrofosmin. We present a case of a 60-year-old woman with a history of a left lung mass awaiting resection. The patient was referred for a myocardial perfusion scan for preoperative risk assessment. The myocardial perfusion scan revealed a large cavitated lesion mimicking a dilated left ventricle and the CT scan revealed a large mass in the left lung with central necrosis displacing the heart and mediastinum. The patient underwent thoracotomy with resection of the mass and the histology confirmed atypical carcinoid. This case highlights noncardiac uptake of Tc-99m tetrofosmin in an atypical carcinoid.

  8. A General Approach to the Evaluation of Ventilation-Perfusion Ratios in Normal and Abnormal Lungs

    ERIC Educational Resources Information Center

    Wagner, Peter D.

    1977-01-01

    Outlines methods for manipulating multiple gas data so as to gain the greatest amount of insight into the properties of ventilation-perfusion distributions. Refers to data corresponding to normal and abnormal lungs. Uses a two-dimensional framework with the respiratory gases of oxygen and carbon dioxide. (CS)

  9. Thromboxane release from irradiated perfused rat lungs: role of oncotic agents

    SciTech Connect

    Heinz, T.R.; Kot, P.A.; Ramwell, P.W.; Schneidkraut, M.J.

    1987-07-27

    Isolated lungs from 20 Gray (Gy) whole body irradiated rats were perfused with Krebs-Ringer bicarbonate plus 3% bovine serum albumin (KRB-BSA). The pulmonary effluent showed a 99% (p < .05) increase in immunoassayable thromboxane B2 (iTXB2) release compared with non-irradiated lungs. Since both arachidonic acid and cyclooxygenase products bind to albumin, studies were performed to determine if omission or substitution of this protein oncotic agent would alter the radiation-induced increase in pulmonary iTXB2 release. Irradiated, isolated lungs perfused with media from which the BSA was omitted (KRB) did not demonstrate the radiation-induced increase in pulmonary iTXB2 release. Similarly, irradiated lungs perfused with media in which Dextran 70 (KRB plus 3% Dextran 70, KRB-Dextran 70) was substituted for BSA also did not show the radiation-induced increase in pulmonary effluent iTXB2 levels. These studies demonstrate the importance of including albumin as the oncotic agent in perfused organ systems when studying cyclooxygenase product release. 23 references, 2 tables.

  10. A General Approach to the Evaluation of Ventilation-Perfusion Ratios in Normal and Abnormal Lungs

    ERIC Educational Resources Information Center

    Wagner, Peter D.

    1977-01-01

    Outlines methods for manipulating multiple gas data so as to gain the greatest amount of insight into the properties of ventilation-perfusion distributions. Refers to data corresponding to normal and abnormal lungs. Uses a two-dimensional framework with the respiratory gases of oxygen and carbon dioxide. (CS)

  11. First steps in membrane oxygenation and prolonged extracorporeal perfusion in Duesseldorf using the Bramson membrane lung.

    PubMed

    Schulte, Hagen D

    2003-05-01

    After a shortened history of conventional closed and open heart surgery, including hypothermia by surface cooling and extracorporeal circulation, the first application of a new membrane oxygenator developed by ML Bramson with an integrated temperature exchange system and a heart-lung machine (HLM) was reported in 1972. The aim was to have an efficient oxygenating and gas exchange artificial lung that allowed prolonged perfusions in patients with cardiogenic shock or acute respiratory insufficiency. After in vitro closed recirculation studies comparing different bubble, vertical screen, and the new membrane oxygenators, the Bramson HLM was used in dog experiments before starting clinical cardiac surgery with routine interventions (closure of an atrial septal defect). The first clinically prolonged support for more than three hours after a double valve replacement in a NYHA class IV patient failed. A partial venoarterial prolonged perfusion for 42 hours and 43 minutes in a 10-year-old girl after surgical correction of a partial av canal defect and postoperative development of consistent lung edema caused by myocardial failure after an ischemic time of 43 minutes was the first successful long-term perfusion case in Europe. These first experiences with the Bramson membrane lung formed the basis, in our group, for further investigations of different perfusion routes and cannulations in animal experiments. Also, scanning electron microscopy studies could be performed with experimentally and clinically used membranes. The development of disposable membrane lung devices, for instance, Lande-Edwards, Kolobow Scimed, and General Electric Peirce membrane lungs, ameliorated and improved the use of these devices considerably. Also, BRAMSON had developed a disposable membrane lung device that had proved to be very effective in animal experiments by 1972, but, unfortunately, this device did not become commercially available.

  12. Active Oxygen Metabolites and Thromboxane in Phorbol Myristate Acetate Toxicity to the Isolated, Perfused Rat Lung.

    NASA Astrophysics Data System (ADS)

    Carpenter, Laurie Jean

    When administered intravenously or intratracheally to rats, rabbits and sheep, phorbol myristate acetate (PMA) produces changes in lung morphology and function are similar to those seen in humans with the adult respiratory distress syndrome (ARDS). Therefore, it is thought that information about the mechanism of ARDS development can be gained from experiments using PMA-treated animals. Currently, the mechanisms by which PMA causes pneumotoxicity are unknown. Results from other studies in rabbits and in isolated, perfused rabbit lungs suggest that PMA-induced lung injury is mediated by active oxygen species from neutrophils (PMN), whereas studies in sheep and rats suggest that PMN are not required for the toxic response. The role of PMN, active oxygen metabolites and thromboxane (TxA_2) in PMA-induced injury to isolated, perfused rat lungs (IPLs) was examined in this thesis. To determine whether PMN were required for PMA to produce toxicity to the IPL, lungs were perfused for 30 min with buffer containing various concentrations of PMA (in the presence or absence of PMN). When concentrations >=q57 ng/ml were added to medium devoid of added PMN, perfusion pressure and lung weight increased. When a concentration of PMA (14-28 ng/ml) that did not by itself cause lungs to accumulate fluid was added to the perfusion medium containing PMN (1 x 10 ^8), perfusion pressure increased, and lungs accumulated fluid. These results indicate that high concentrations of PMA produce lung injury which is independent of PMN, whereas injury induced by lower concentrations is PMN-dependent. To examine whether active oxygen species were involved in mediating lung injury induced by PMA and PMN, lungs were coperfused with the oxygen radical scavengers SOD and/or catalase. Coperfusion with either or both of these enzymes totally protected lungs against injury caused by PMN and PMA. These results suggest that active oxygen species (the hydroxyl radical in particular), mediate lung injury in

  13. Quantifying Single Microvessel Permeability in Isolated Blood-perfused Rat Lung Preparation

    PubMed Central

    Kandasamy, Kathirvel; Parthasarathi, Kaushik

    2014-01-01

    The isolated blood-perfused lung preparation is widely used to visualize and define signaling in single microvessels. By coupling this preparation with real time imaging, it becomes feasible to determine permeability changes in individual pulmonary microvessels. Herein we describe steps to isolate rat lungs and perfuse them with autologous blood. Then, we outline steps to infuse fluorophores or agents via a microcatheter into a small lung region. Using these procedures described, we determined permeability increases in rat lung microvessels in response to infusions of bacterial lipopolysaccharide. The data revealed that lipopolysaccharide increased fluid leak across both venular and capillary microvessel segments. Thus, this method makes it possible to compare permeability responses among vascular segments and thus, define any heterogeneity in the response. While commonly used methods to define lung permeability require postprocessing of lung tissue samples, the use of real time imaging obviates this requirement as evident from the present method. Thus, the isolated lung preparation combined with real time imaging offers several advantages over traditional methods to determine lung microvascular permeability, yet is a straightforward method to develop and implement. PMID:25045895

  14. Perfusion lung scintigraphy for the prediction of postoperative residual pulmonary function in patients with lung cancer.

    PubMed

    Kovacević-Kuśmierek, Katarzyna; Kozak, Józef; Pryt, Łukasz; Bieńkiewicz, Małgorzata; Cichocki, Paweł; Kuśmierek, Jacek; Płachcińska, Anna

    2015-01-01

    Accurate prediction of postoperative pulmonary function in patients with non-small cell lung cancer is crucial for proper qualification for surgery, the only effective therapeutic method. The aim of the study was to select the most accurate method for acquisition and processing of lung perfusion scintigraphy (LPS) combined with spirometry for prediction of postoperative pulmonary function in patients qualified for surgery. LPS was performed in 70 patients (40 males, 30 females), with preoperative spirometry (mean FEV1preop = 2.26 ± 0.72 L), after administration of 185 MBq of 99mTc-microalbumin/macroaggregate, using planar (appa) and SPECT/CT methods. Predicted postoperative lung function (FEV1pred) was calculated as a part of active lung parenchyma to remain after surgery. A non-imaging segment counting method was also applied. FEV1pred(appa, SPECT, SPECT/CT, segm.) were further compared with actual FEV1postop values obtained from postoperative spirometry. In the whole studied group (47 lobectomies, 23 pneumonectomies) mean value of FEV1postop was equal to 1.76 (± 0.56) L. FEV1pred(appa, SPECT, SPECT/CT, segm.) were equal to 1.75 (± 0.58) L, 1.71 (± 0.57) L, 1.72 (± 0.57) L and 1.57 (± 0.58) L, respectively. A segment counting method systematically lowered predicted FEV1 values (p < 10-5). Moreover, in 31 patients with FEV1preop < 2 L error of predicted values was assessed with Bland-Altman method. Mean absolute differences FEV1postop - FEV1pred amounted to: appa - (0.04 ± 0.13) L, SPECT - (0.07 ± 0.14) L, SPECT/CT - (0.06 ± 0.14) L and segm. - (0.21 ± 0.19) L, respectively. Lower limit of 95% confidence interval calculated for planar - optimal method, was equal to -220 mL (also determined separately in subgroups after lobectomy and pneumonectomy). This study shows that planar LPS may be applied for prediction of postoperative pulmonary function in patients qualified for pneumonectomy and lobectomy. If actual FEV1postop value is to be ≥ 800 m

  15. [Lung perfusion studies after percutaneous closure of patent ductus arteriosus using the Amplatzer Duct Occluder in children].

    PubMed

    Parra-Bravo, José Rafael; Apolonio-Martínez, Adriana; Estrada-Loza, María de Jesús; Beirana-Palencia, Luisa Gracia; Ramírez-Portillo, César Iván

    2015-01-01

    The closure of patent ductus arteriosus with multiple devices has been associated with a reduction in lung perfusion. We evaluated the pulmonary perfusion after percutaneous closure of patent ductus arteriosus with the Amplatzer Duct Occluder device using perfusion lung scan. Thirty patients underwent successful percutaneous patent ductus arteriosus occlusions using the Amplatzer Duct Occluder device were included in this study. Lung perfusion scans were preformed 6 months after the procedure. Peak flow velocities and protrusion of the device were analyzed by Doppler echocardiography. A left lung perfusion<40% was considered abnormal. The device implantation was successful in all patients. Average perfusion of left lung was 44.7±4.9% (37.8-61.4). Five patients (16.6%) showed decreased perfusion of the left lung. Age, low weight, the length of the ductus arteriosus and the minimum and maximum diameter/length of the ductus arteriosus ratio were statistically significant in patients with abnormalities of lung perfusion. It was observed protrusion the device in 6 patients with a higher maximum flow rate in the left pulmonary artery. The left lung perfusion may be compromised after percutaneous closure of patent ductus arteriosus with the Amplatzer Duct Occluder. The increased flow velocity in the origin of the left pulmonary artery can be a poor indicator of reduction in pulmonary perfusion and can occur in the absence of protrusion of the device. Copyright © 2014 Instituto Nacional de Cardiología Ignacio Chávez. Published by Masson Doyma México S.A. All rights reserved.

  16. Improvement in Ventilation-Perfusion Mismatch after Bronchoscopic Lung Volume Reduction: Quantitative Image Analysis.

    PubMed

    Lee, Sei Won; Lee, Sang Min; Shin, So Youn; Park, Tai Sun; Oh, Sang Young; Kim, Namkug; Hong, Yoonki; Lee, Jae Seung; Oh, Yeon-Mok; Lee, Sang-Do; Seo, Joon Beom

    2017-10-01

    Purpose To evaluate whether bronchoscopic lung volume reduction (BLVR) increases ventilation and therefore improves ventilation-perfusion (V/Q) mismatch. Materials and Methods All patients provided written informed consent to be included in this study, which was approved by the Institutional Review Board (2013-0368) of Asan Medical Center. The physiologic changes that occurred after BLVR were measured by using xenon-enhanced ventilation and iodine-enhanced perfusion dual-energy computed tomography (CT). Patients with severe emphysema plus hyperinflation who did not respond to usual treatments were eligible. Pulmonary function tests, the 6-minute walking distance (6MWD) test, quality of life assessment, and dual-energy CT were performed at baseline and 3 months after BLVR. The effect of BLVR was assessed with repeated-measures analysis of variance. Results Twenty-one patients were enrolled in this study (median age, 68 years; mean forced expiratory volume in 1 second [FEV1], 0.75 L ± 0.29). After BLVR, FEV1 (P < .001) and 6MWD (P = .002) improved significantly. Despite the reduction in lung volume (-0.39 L ± 0.44), both ventilation per voxel (P < .001) and total ventilation (P = .01) improved after BLVR. However, neither perfusion per voxel (P = .16) nor total perfusion changed significantly (P = .49). Patients with lung volume reduction of 50% or greater had significantly better improvement in FEV1 (P = .02) and ventilation per voxel (P = .03) than patients with lung volume reduction of less than 50%. V/Q mismatch also improved after BLVR (P = .005), mainly owing to the improvement in ventilation. Conclusion The dual-energy CT analyses showed that BLVR improved ventilation and V/Q mismatch. This increased lung efficiency may be the primary mechanism of improvement after BLVR, despite the reduction in lung volume. (©) RSNA, 2017 Online supplemental material is available for this article.

  17. Ex vivo lung perfusion with adenosine A2A receptor agonist allows prolonged cold preservation of lungs donated after cardiac death.

    PubMed

    Wagner, Cynthia E; Pope, Nicolas H; Charles, Eric J; Huerter, Mary E; Sharma, Ashish K; Salmon, Morgan D; Carter, Benjamin T; Stoler, Mark H; Lau, Christine L; Laubach, Victor E; Kron, Irving L

    2016-02-01

    Ex vivo lung perfusion has been successful in the assessment of marginal donor lungs, including donation after cardiac death (DCD) donor lungs. Ex vivo lung perfusion also represents a unique platform for targeted drug delivery. We sought to determine whether ischemia-reperfusion injury would be decreased after transplantation of DCD donor lungs subjected to prolonged cold preservation and treated with an adenosine A2A receptor agonist during ex vivo lung perfusion. Porcine DCD donor lungs were preserved at 4°C for 12 hours and underwent ex vivo lung perfusion for 4 hours. Left lungs were then transplanted and reperfused for 4 hours. Three groups (n = 4/group) were randomized according to treatment with the adenosine A2A receptor agonist ATL-1223 or the dimethyl sulfoxide vehicle: Infusion of dimethyl sulfoxide during ex vivo lung perfusion and reperfusion (DMSO), infusion of ATL-1223 during ex vivo lung perfusion and dimethyl sulfoxide during reperfusion (ATL-E), and infusion of ATL-1223 during ex vivo lung perfusion and reperfusion (ATL-E/R). Final Pao2/Fio2 ratios (arterial oxygen partial pressure/fraction of inspired oxygen) were determined from samples obtained from the left superior and inferior pulmonary veins. Final Pao2/Fio2 ratios in the ATL-E/R group (430.1 ± 26.4 mm Hg) were similar to final Pao2/Fio2 ratios in the ATL-E group (413.6 ± 18.8 mm Hg), but both treated groups had significantly higher final Pao2/Fio2 ratios compared with the dimethyl sulfoxide group (84.8 ± 17.7 mm Hg). Low oxygenation gradients during ex vivo lung perfusion did not preclude superior oxygenation capacity during reperfusion. After prolonged cold preservation, treatment of DCD donor lungs with an adenosine A2A receptor agonist during ex vivo lung perfusion enabled Pao2/Fio2 ratios greater than 400 mm Hg after transplantation in a preclinical porcine model. Pulmonary function during ex vivo lung perfusion was not predictive of outcomes after transplantation. Copyright

  18. Quantification of lung perfusion blood volume (lung PBV) by dual-energy CT in pulmonary embolism before and after treatment: preliminary results.

    PubMed

    Nagayama, Hiroki; Sueyoshi, Eijun; Hayashida, Takeshi; Ashizawa, Kazuto; Sakamoto, Ichiro; Uetani, Masataka

    2013-01-01

    The purpose was to investigate the quantification of lung perfusion blood volume (PBV) by dual-energy computed tomography (CT) in patients with pulmonary embolism (PE) before and after treatment. Twenty-five patients with PE underwent dual-energy CT angiography before and after treatment. In all 25 patients, pulmonary CT confirmed that there was no PE after treatment. This preliminary study demonstrated the possibility that quantification of lung PBV may reflect parenchymal arterial perfusion before and after treatment, including the compensatory increase of lung perfusion.

  19. Lung perfusion and emphysema distribution affect the outcome of endobronchial valve therapy

    PubMed Central

    Thomsen, Christian; Theilig, Dorothea; Herzog, Dominik; Poellinger, Alexander; Doellinger, Felix; Schreiter, Nils; Schreiter, Vera; Schürmann, Dirk; Temmesfeld-Wollbrueck, Bettina; Hippenstiel, Stefan; Suttorp, Norbert; Hubner, Ralf-Harto

    2016-01-01

    The exclusion of collateral ventilation (CV) and other factors affect the clinical success of endoscopic lung volume reduction (ELVR). However, despite its benefits, the outcome of ELVR remains difficult to predict. We investigated whether clinical success could be predicted by emphysema distribution assessed by computed tomography scan and baseline perfusion assessed by perfusion scintigraphy. Data from 57 patients with no CV in the target lobe (TL) were retrospectively analyzed after ELVR with valves. Pulmonary function tests (PFT), St George’s Respiratory Questionnaire (SGRQ), and 6-minute walk tests (6MWT) were performed on patients at baseline. The sample was grouped into high and low levels at the median of TL perfusion, ipsilateral nontarget lobe (INL) perfusion, and heterogeneity index (HI). These groups were analyzed for association with changes in outcome parameters from baseline to 3 months follow-up. Compared to baseline, patients showed significant improvements in PFT, SGRQ, and 6MWT (all P≤0.001). TL perfusion was not associated with changes in the outcome. High INL perfusion was significantly associated with increases in 6MWT (P=0.014), and high HI was associated with increases in forced expiratory volume in 1 second (FEV1), (P=0.012). Likewise, there were significant correlations for INL perfusion and improvement of 6MWT (r=0.35, P=0.03) and for HI and improvement in FEV1 (r=0.45, P=0.001). This study reveals new attributes that associate with positive outcomes for patient selection prior to ELVR. Patients with high perfusions in INL demonstrated greater improvements in 6MWT, while patients with high HI were more likely to respond in FEV1. PMID:27354783

  20. Automated scoring of regional lung perfusion in children from contrast enhanced 3D MRI

    NASA Astrophysics Data System (ADS)

    Heimann, Tobias; Eichinger, Monika; Bauman, Grzegorz; Bischoff, Arved; Puderbach, Michael; Meinzer, Hans-Peter

    2012-03-01

    MRI perfusion images give information about regional lung function and can be used to detect pulmonary pathologies in cystic fibrosis (CF) children. However, manual assessment of the percentage of pathologic tissue in defined lung subvolumes features large inter- and intra-observer variation, making it difficult to determine disease progression consistently. We present an automated method to calculate a regional score for this purpose. First, lungs are located based on thresholding and morphological operations. Second, statistical shape models of left and right children's lungs are initialized at the determined locations and used to precisely segment morphological images. Segmentation results are transferred to perfusion maps and employed as masks to calculate perfusion statistics. An automated threshold to determine pathologic tissue is calculated and used to determine accurate regional scores. We evaluated the method on 10 MRI images and achieved an average surface distance of less than 1.5 mm compared to manual reference segmentations. Pathologic tissue was detected correctly in 9 cases. The approach seems suitable for detecting early signs of CF and monitoring response to therapy.

  1. Marked differences between prone and supine sheep in effect of PEEP on perfusion distribution in zone II lung.

    PubMed

    Walther, Sten M; Johansson, Mats J; Flatebø, Torun; Nicolaysen, Anne; Nicolaysen, Gunnar

    2005-09-01

    The classic four-zone model of lung blood flow distribution has been questioned. We asked whether the effect of positive end-expiratory pressure (PEEP) is different between the prone and supine position for lung tissue in the same zonal condition. Anesthetized and mechanically ventilated prone (n = 6) and supine (n = 5) sheep were studied at 0, 10, and 20 cm H2O PEEP. Perfusion was measured with intravenous infusion of radiolabeled 15-microm microspheres. The right lung was dried at total lung capacity and diced into pieces (approximately 1.5 cm3), keeping track of the spatial location of each piece. Radioactivity per unit weight was determined and normalized to the mean value for each condition and animal. In the supine posture, perfusion to nondependent lung regions decreased with little relative perfusion in nondependent horizontal lung planes at 10 and 20 cm H2O PEEP. In the prone position, the effect of PEEP was markedly different with substantial perfusion remaining in nondependent lung regions and even increasing in these regions with 20 cm H2O PEEP. Vertical blood flow gradients in zone II lung were large in supine, but surprisingly absent in prone, animals. Isogravitational perfusion heterogeneity was smaller in prone than in supine animals at all PEEP levels. Redistribution of pulmonary perfusion by PEEP ventilation in supine was largely as predicted by the zonal model in marked contrast to the findings in prone. The differences between postures in blood flow distribution within zone II strongly indicate that factors in addition to pulmonary arterial, venous, and alveolar pressure play important roles in determining perfusion distribution in the in situ lung. We suggest that regional variation in lung volume through the effect on vascular resistance is one such factor and that chest wall conformation and thoracic contents determine regional lung volume.

  2. Generation of parametric images during routine Tc-99m PYP inhalation/Tc-99m MAA perfusion lung scintigraphy. Technical note.

    PubMed

    Miron, S D; Wiesen, E J; Feiglin, D H; Cohen, A M; Bellon, E M

    1991-07-01

    A simple technique is described for generating ventilation/perfusion ratio and perfusion/ventilation ratio images from the posterior Tc-99m PYP aerosol inhalation and Tc-99m MAA perfusion images obtained during routine lung scintigraphy. These images highlight areas of ventilation/perfusion incongruence--mismatch or reverse mismatch--that may sometimes be difficult to detect on conventional images.

  3. Isolated total lung perfusion as a means to deliver organ-specific chemotherapy: long-term studies in animals

    SciTech Connect

    Johnston, M.R.; Christensen, C.W.; Minchin, R.F.; Rickaby, D.A.; Linehan, J.H.; Schuller, H.M.; Boyd, M.R.; Dawson, C.A.

    1985-07-01

    The objectives of this study were to develop a surgical procedure that would allow for bilateral isolated lung perfusion in vivo as a means of delivering organ-specific chemotherapy and to evaluate the influence of the procedure on certain pulmonary physiologic parameters. The sterile surgical procedure that was carried out in dogs involved the setting up of two separate perfusion circuits. Once standard systemic cardiopulmonary bypass was established, a second circuit was devised to perfuse the lungs by placing an inflow cannula into the main pulmonary artery and collecting venous effluent in the left atrium. Cross-contamination between perfusion circuits was determined in acute studies with labeled plasma protein or red blood cells and was found to be in an acceptable range if the aorta was cross-clamped and the heart arrested. Only about 0.4 ml/min of pulmonary perfusate leaked into the systemic circulation, indicating that systemic toxicity should not be a major concern when chemotherapy agents are added to the pulmonary perfusate. Chronic studies demonstrated that hemodynamic parameters, lung water, pulmonary endothelial serotonin extraction, and histologic findings all showed minimal changes after 50 minutes of isolated lung perfusion. Five days after perfusion, lung dynamic compliance and peak serotonin extraction showed significant decreases. However, all of the measured parameters had returned toward baseline levels by the end of the 8-week postoperative study period. The procedure offers significant advantages over the previously described single lung perfusion and may provide a method of delivering immediate high-concentration adjuvant chemotherapy to coincide with resection of primary or metastatic lung tumors.

  4. Preparation of Tc-99m-macroaggregated albumin from recombinant human albumin for lung perfusion imaging.

    PubMed

    Hunt, A P; Frier, M; Johnson, R A; Berezenko, S; Perkins, A C

    2006-01-01

    Human serum albumin (HSA) extracted from pooled blood taken from human donors is used in the production of (99m)Tc-labelled macroaggregated albumin (MAA) for lung perfusion imaging. However, concerns for the safety of blood-derived products due to potential contamination by infective agents (e.g. new variant CJD), make alternative production methods necessary. Recombinant DNA technology is a promising method of albumin production avoiding problems associated with human-derived HSA. This paper presents results comparing MAA prepared from recombinant human albumin (rHA, Recombumin) (rMAA) with in-house produced HSA MAA (hMAA) and commercially available MAA (cMAA). (99m)Tc-MAA was prepared using previously published production methods by heating a mixture of albumin and stannous chloride in acetate buffer (pH 5.4) at 70 degrees C for 20 min. Parameters investigated include aggregate size, radiolabelling efficiency, radiochemical and aggregate stability at 4 degrees C and in vitro (in whole human blood) at 37 degrees C and biodistribution studies. Results showed that rMAA could be produced with similar morphology, labelling efficiency and stability to hMAA and cMAA. Our findings confirm that rHA shows significant potential as a direct replacement for HSA in commercially available MAA.

  5. Ventilation/Perfusion Positron Emission Tomography—Based Assessment of Radiation Injury to Lung

    SciTech Connect

    Siva, Shankar; Hardcastle, Nicholas; Kron, Tomas; Bressel, Mathias; Callahan, Jason; MacManus, Michael P.; Shaw, Mark; Plumridge, Nikki; Hicks, Rodney J.; Steinfort, Daniel; Ball, David L.; Hofman, Michael S.

    2015-10-01

    Purpose: To investigate {sup 68}Ga-ventilation/perfusion (V/Q) positron emission tomography (PET)/computed tomography (CT) as a novel imaging modality for assessment of perfusion, ventilation, and lung density changes in the context of radiation therapy (RT). Methods and Materials: In a prospective clinical trial, 20 patients underwent 4-dimensional (4D)-V/Q PET/CT before, midway through, and 3 months after definitive lung RT. Eligible patients were prescribed 60 Gy in 30 fractions with or without concurrent chemotherapy. Functional images were registered to the RT planning 4D-CT, and isodose volumes were averaged into 10-Gy bins. Within each dose bin, relative loss in standardized uptake value (SUV) was recorded for ventilation and perfusion, and loss in air-filled fraction was recorded to assess RT-induced lung fibrosis. A dose-effect relationship was described using both linear and 2-parameter logistic fit models, and goodness of fit was assessed with Akaike Information Criterion (AIC). Results: A total of 179 imaging datasets were available for analysis (1 scan was unrecoverable). An almost perfectly linear negative dose-response relationship was observed for perfusion and air-filled fraction (r{sup 2}=0.99, P<.01), with ventilation strongly negatively linear (r{sup 2}=0.95, P<.01). Logistic models did not provide a better fit as evaluated by AIC. Perfusion, ventilation, and the air-filled fraction decreased 0.75 ± 0.03%, 0.71 ± 0.06%, and 0.49 ± 0.02%/Gy, respectively. Within high-dose regions, higher baseline perfusion SUV was associated with greater rate of loss. At 50 Gy and 60 Gy, the rate of loss was 1.35% (P=.07) and 1.73% (P=.05) per SUV, respectively. Of 8/20 patients with peritumoral reperfusion/reventilation during treatment, 7/8 did not sustain this effect after treatment. Conclusions: Radiation-induced regional lung functional deficits occur in a dose-dependent manner and can be estimated by simple linear models with 4D-V/Q PET

  6. Vasomotor tone does not affect perfusion heterogeneity and gas exchange in normal primate lungs during normoxia

    NASA Technical Reports Server (NTRS)

    Glenny, R. W.; Robertson, H. T.; Hlastala, M. P.

    2000-01-01

    To determine whether vasoregulation is an important cause of pulmonary perfusion heterogeneity, we measured regional blood flow and gas exchange before and after giving prostacyclin (PGI(2)) to baboons. Four animals were anesthetized with ketamine and mechanically ventilated. Fluorescent microspheres were used to mark regional perfusion before and after PGI(2) infusion. The lungs were subsequently excised, dried inflated, and diced into approximately 2-cm(3) pieces (n = 1,208-1,629 per animal) with the spatial coordinates recorded for each piece. Blood flow to each piece was determined for each condition from the fluorescent signals. Blood flow heterogeneity did not change with PGI(2) infusion. Two other measures of spatial blood flow distribution, the fractal dimension and the spatial correlation, did not change with PGI(2) infusion. Alveolar-arterial O(2) differences did not change with PGI(2) infusion. We conclude that, in normal primate lungs during normoxia, vasomotor tone is not a significant cause of perfusion heterogeneity. Despite the heterogeneous distribution of blood flow, active regulation of regional perfusion is not required for efficient gas exchange.

  7. Vasomotor tone does not affect perfusion heterogeneity and gas exchange in normal primate lungs during normoxia

    NASA Technical Reports Server (NTRS)

    Glenny, R. W.; Robertson, H. T.; Hlastala, M. P.

    2000-01-01

    To determine whether vasoregulation is an important cause of pulmonary perfusion heterogeneity, we measured regional blood flow and gas exchange before and after giving prostacyclin (PGI(2)) to baboons. Four animals were anesthetized with ketamine and mechanically ventilated. Fluorescent microspheres were used to mark regional perfusion before and after PGI(2) infusion. The lungs were subsequently excised, dried inflated, and diced into approximately 2-cm(3) pieces (n = 1,208-1,629 per animal) with the spatial coordinates recorded for each piece. Blood flow to each piece was determined for each condition from the fluorescent signals. Blood flow heterogeneity did not change with PGI(2) infusion. Two other measures of spatial blood flow distribution, the fractal dimension and the spatial correlation, did not change with PGI(2) infusion. Alveolar-arterial O(2) differences did not change with PGI(2) infusion. We conclude that, in normal primate lungs during normoxia, vasomotor tone is not a significant cause of perfusion heterogeneity. Despite the heterogeneous distribution of blood flow, active regulation of regional perfusion is not required for efficient gas exchange.

  8. Reversibility of intrapulmonary arteriovenous shunts in liver cirrhosis documented by serial radionuclide perfusion lung scans

    SciTech Connect

    Chen, N.S.; Barnett, C.A.; Farrer, P.A.

    1984-05-01

    Using serial perfusion lung scans, the opening up and closure of right-to-left intrapulmonary arteriovenous shunts has been documented over a period of several weeks in a patient with chronic alcoholic liver disease. The presence of the shunts correlates well with the severity of hypoxemia and the presence of nodular mottling on chest radiographs. The time course of these changes with clinical status suggests lability and the functional nature of these shunts.

  9. Analysis of perfusates during hypothermic machine perfusion by NMR spectroscopy: a potential tool for predicting kidney graft outcome.

    PubMed

    Bon, Delphine; Billault, Claire; Claire, Billault; Thuillier, Raphaël; Hebrard, William; Boildieu, Nadège; Celhay, Olivier; Irani, Jacques; Seguin, François; Hauet, Thierry

    2014-04-27

    Machine perfusion use has been reported to promote graft outcome in case of donation after cardiac death. Our objective was to evaluate the potential for nuclear magnetic resonance (NMR) to predict graft outcome by analyzing perfusates during machine perfusion time. We used a renal autotransplantation model mimicking deceased after cardiac death donors with pigs. Organs were subjected to 60 min of warm ischemia before the hypothermic machine preservation during 22 hr. We studied the correlation between creatinemia after transplantation and the NMR data from perfusates. A metabonomic analysis allowed us to highlight the evolution of several metabolites during perfusion: the concentration of lactate, choline, or amino acids such as valine, glycine, or glutamate increased with time, whereas there was a diminution of total glutathione during this period. The changes in these biomarkers were less severe in the group with the better outcome. Statistical analysis revealed a strong association between the level of those metabolites during machine perfusion and function recovery (Spearman rank ≥0.89; P<0.05). Multivariate analysis of lesion biomarkers during kidney perfusion using NMR data could be an interesting tool to assess graft quality, particularly because analyses times (2 hr total) are compatible with clinical application.

  10. Optical studies of tissue mitochondrial redox in isolated perfused rat lungs

    NASA Astrophysics Data System (ADS)

    Sepehr, R.; Staniszewski, K.; Jacobs, E. R.; Audi, S.; Ranji, M.

    2012-02-01

    Through the monitoring of the auto-fluorescent mitochondrial metabolic coenzymes, NADH (Nicotinamide Adenine Dinucleotide) and FAD (Flavoprotein Adenine Dinucleotide), the redox state of metabolism can be probed in real time in many intact organs, but its use has not been fully developed in lungs. The ratio of these fluorophores, (NADH/FAD), referred to as the mitochondrial redox ratio (RR), can be used as a quantitative metabolic marker of tissue. We have designed a fluorometer that can be used to monitor lung surface NADH and FAD fluorescence in isolated perfused lungs. Surface fluorescence NADH and FAD signals were acquired in the absence (control) and presence of pentachlorophenol (PCP), rotenone, and potassium cyanide (KCN). Rotenone, an inhibitor of complex I, increased RR by 18%, predominantly due to an increase in NADH signal. KCN, an inhibitor of complex IV reduced the chain and resulted in an increase of 33% in RR, as a result of 23% increase in NADH and 8% in FAD . PCP, an uncoupler which oxidizes the respiratory chain, decreased RR by 18% as a result of 14% decrease in NADH signal and 4% increase in FAD signal. These results demonstrate the ability of surface fluorometry to detect changes in lung tissue mitochondrial redox state in isolated perfused lungs.

  11. Role of inhaled nitric oxide in ischaemia-reperfusion injury in the perfused rabbit lung.

    PubMed

    Ishibe, Y; Liu, R; Ueda, M; Mori, K; Miura, N

    1999-09-01

    We have tested if inhaled nitric oxide (NO) is beneficial in ischaemia-reperfusion (IR) lung injury using an isolated perfused rabbit lung model. Ischaemia for 60 min was followed by reperfusion and ventilation with nitric oxide 40 ppm (n = 6) or without nitric oxide ventilation (n = 6) for 60 min. In the control group (n = 6), the lungs were perfused continuously for 120 min. Permeability coefficient (Kfc) and vascular resistance (PVR) were measured serially for 60 min after reperfusion. We also determined the left lung W/D ratio and measured nitric oxide metabolites (NOx) and cGMP concentrations in bronchoalveolar lavage (BAL) fluid from the right lung. IR increased Kfc, PVR and W/D followed by decreased cGMP. Ventilation with nitric oxide restored these changes by preventing the decrease in cGMP. Differences in NOx concentrations in BAL fluid between the control and IR groups were not statistically significant. Our results indicate that IR impaired pulmonary vascular function and resulted in microvascular constriction and leakage. Ventilation with nitric oxide from the beginning of the reperfusion period improved pulmonary dysfunction such as vasoconstriction and capillary leak by restoring cGMP concentrations.

  12. First in vivo magnetic particle imaging of lung perfusion in rats.

    PubMed

    Zhou, Xinyi Yedda; Jeffris, Kenneth; Yu, Elaine; Zheng, Bo; Goodwill, Patrick; Nahid, Payam; Conolly, Steven

    2017-02-20

    Pulmonary embolism (PE), along with the closely related condition of deep vein thrombosis, affect an estimated 600,000 patients in the US per year. Untreated, PE carries a mortality rate of 30%. Because many patients experience mild or non-specific symptoms, imaging studies are necessary for definitive diagnosis of PE. Iodinated CT pulmonary angiography (CTPA) is recommended for most patients, while nuclear medicine-based ventilation/perfusion (V/Q) scans are reserved for patients in whom the use of iodine is contraindicated. Magnetic particle imaging (MPI) is an emerging tracer imaging modality with high image contrast (no tissue background signal) and sensitivity (200 nM Fe) to superparamagnetic iron oxide (SPIO) tracer. Importantly, unlike CT or nuclear medicine, MPI uses no ionizing radiation. Further, MPI is not derived from magnetic resonance imaging (MRI); MPI directly images SPIO tracers via their strong electronic magnetization, enabling deep imaging of anatomy including within the lungs, which is very challenging with MRI. Here, the first high-contrast in vivo MPI lung perfusion images of rats are shown using a novel lung perfusion agent, MAA-SPIOs.

  13. First in vivo magnetic particle imaging of lung perfusion in rats

    NASA Astrophysics Data System (ADS)

    Zhou, Xinyi Y.; Jeffris, Kenneth E.; Yu, Elaine Y.; Zheng, Bo; Goodwill, Patrick W.; Nahid, Payam; Conolly, Steven M.

    2017-05-01

    Pulmonary embolism (PE), along with the closely related condition of deep vein thrombosis, affect an estimated 600 000 patients in the US per year. Untreated, PE carries a mortality rate of 30%. Because many patients experience mild or non-specific symptoms, imaging studies are necessary for definitive diagnosis of PE. Iodinated CT pulmonary angiography is recommended for most patients, while nuclear medicine-based ventilation/perfusion (V/Q) scans are reserved for patients in whom the use of iodine is contraindicated. Magnetic particle imaging (MPI) is an emerging tracer imaging modality with high image contrast (no tissue background signal) and sensitivity to superparamagnetic iron oxide (SPIO) tracer. Importantly, unlike CT or nuclear medicine, MPI uses no ionizing radiation. Further, MPI is not derived from magnetic resonance imaging (MRI); MPI directly images SPIO tracers via their strong electronic magnetization, enabling deep imaging of anatomy including within the lungs, which is very challenging with MRI. Here, the first high-contrast in vivo MPI lung perfusion images of rats are shown using a novel lung perfusion agent, MAA-SPIOs.

  14. SU-F-BRF-11: Dose Rearrangement in High Dose Locally Advanced Lung Patients Based On Perfusion Imaging

    SciTech Connect

    Matrosic, C; Jarema, D; Kong, F; McShan, D; Stenmark, M; Owen, D; Ten Haken, R; Matuszak, M

    2014-06-15

    Purpose: The use of mean lung dose (MLD) limits allows individualization of lung patient tumor doses at safe levels. However, MLD does not account for local lung function differences between patients, leading to toxicity variability at the same MLD. We investigated dose rearrangement to minimize dose to functional lung, as measured by perfusion SPECT, while maintaining target coverage and conventional MLD limits. Methods: Retrospective plans were optimized for 15 locally advanced NSCLC patients enrolled in a prospective imaging trial. A priority-based optimization system was used. The baseline priorities were (1) meet OAR dose constraints, (2) maximize target gEUD, and (3) minimize physical MLD. As a final step, normal tissue doses were minimized. To determine the benefit of rearranging dose using perfusion SPECT, plans were reoptimized to minimize functional lung gEUD as the 4th priority. Results: When only minimizing physical MLD, the functional lung gEUD was 10.8+/−5.0 Gy (4.3–19.8 Gy). Only 3/15 cases showed a decrease in functional lung gEUD of ≥4% when rearranging dose to minimize functional gEUD in the cost function (10.5+/−5.0 Gy range 4.3−19.7). Although OAR constraints were respected, the dose rearrangement resulted in ≥10% increases in gEUD to an OAR in 4/15 cases. Only slight reductions in functional lung gEUD were noted when omitting the minimization of physical MLD, suggesting that constraining the target gEUD minimizes the potential to redistribute dose. Conclusion: Prioritydriven optimization permits the generation of plans that respect traditional OAR limits and target coverage, but with the ability to rearrange dose based on functional imaging. The latter appears to be limited due to the decreased solution space when constraining target coverage. Since dose rearrangement may increase dose to other OARs, it is also worthwhile to investigate global biomarkers of lung toxicity to further individualize treatment in this population

  15. Protease inhibitor nafamostat mesilate attenuates complement activation and improves function of xenografts in a discordant lung perfusion model.

    PubMed

    Tagawa, Tsutomu

    2011-01-01

    Anti-complement activity of nafamostat mesilate (FUT-175) is strong including its variety of pharmacological effects. The effect of FUT-175 for xenografts in an ex vivo guinea pig-to-rat lung perfusion model was evaluated. Heparinized Lewis rat blood was used to perfuse the lungs in three groups (n = 6 each). Group I used Lewis rat left lung for donor, Group X used guinea pig left lung for donor, and Group XF used guinea pig left lung for donor, which was perfused with Lewis rat blood with 0.2 mg/ml of FUT-175. Complement activity causing 50% hemolysis (CH50) in the perfusion blood and pulmonary function either before or during perfusion were serially measured. Pathological assessments of the lungs were also carried out after perfusion. The duration of satisfactory pulmonary function was significantly increased in Group XF. Complement activity causing 50% hemolysis in Group XF decreased more significantly compared to Group X. FUT-175 suppressed both the increase in pulmonary arterial pressure and airway resistance, and the decrease in dynamic lung compliance. In Group X, pathology showed intra-alveolar hemorrhage, perivascular edema, and medial thickening with endothelial swelling of the pulmonary arteries. In Group XF, less changes were observed compared to Group X. Group X showed deposition of IgM, IgG, and C3 at the endothelium of arteries, which was fewer in Group XF, and even fewer in Group I. This study suggests that FUT-175 inhibited complement activation and improved lung xenograft function. FUT-175 ameliorates hyperacute rejection in a guinea pig-to-rat ex vivo xenogeneic lung perfusion model. © 2011 John Wiley & Sons A/S.

  16. Radiation-Induced Reductions in Regional Lung Perfusion: 0.1-12 Year Data From a Prospective Clinical Study

    SciTech Connect

    Zhang Junan; Ma Jinli; Zhou Sumin; Hubbs, Jessica L.; Wong, Terence Z.; Folz, Rodney J.; Evans, Elizabeth S.; Jaszczak, Ronald J.; Clough, Robert; Marks, Lawrence B.

    2010-02-01

    Purpose: To assess the time and regional dependence of radiation therapy (RT)-induced reductions in regional lung perfusion 0.1-12 years post-RT, as measured by single photon emission computed tomography (SPECT) lung perfusion. Materials/Methods: Between 1991 and 2005, 123 evaluable patients receiving RT for tumors in/around the thorax underwent SPECT lung perfusion scans before and serially post-RT (0.1-12 years). Registration of pre- and post-RT SPECT images with the treatment planning computed tomography, and hence the three-dimensional RT dose distribution, allowed changes in regional SPECT-defined perfusion to be related to regional RT dose. Post-RT follow-up scans were evaluated at multiple time points to determine the time course of RT-induced regional perfusion changes. Population dose response curves (DRC) for all patients at different time points, different regions, and subvolumes (e.g., whole lungs, cranial/caudal, ipsilateral/contralateral) were generated by combining data from multiple patients at similar follow-up times. Each DRC was fit to a linear model, and differences statistically analyzed. Results: In the overall groups, dose-dependent reductions in perfusion were seen at each time post-RT. The slope of the DRC increased over time up to 18 months post-RT, and plateaued thereafter. Regional differences in DRCs were only observed between the ipsilateral and contralateral lungs, and appeared due to tumor-associated changes in regional perfusion. Conclusions: Thoracic RT causes dose-dependent reductions in regional lung perfusion that progress up to {approx}18 months post-RT and persists thereafter. Tumor shrinkage appears to confound the observed dose-response relations. There appears to be similar dose response for healthy parts of the lungs at different locations.

  17. Perfusion-Decellularization of Porcine Lung and Trachea for Respiratory Bioengineering.

    PubMed

    Weymann, Alexander; Patil, Nikhil Prakash; Sabashnikov, Anton; Korkmaz, Sevil; Li, Shiliang; Soos, Pal; Ishtok, Roland; Chaimow, Nicole; Pätzold, Ines; Czerny, Natalie; Schmack, Bastian; Popov, Aron-Frederik; Simon, Andre Rüdiger; Karck, Matthias; Szabo, Gabor

    2015-12-01

    Decellularization of native organs may provide an acellular tissue platform for organ regeneration. However, decellularization involves a trade-off between removal of immunogenic cellular elements and preservation of biomechanical integrity. We sought to develop a bioartificial scaffold for respiratory tissue engineering by decellularization of porcine lungs and trachea while preserving organ architecture and vasculature. Lung-trachea preparations from 25 German Landrace pigs were perfused in a modified Langendorff circuit and decellularized by an SDC (sodium deoxycholate)-based perfusion protocol. Decellularization was evaluated by histology and fluorescence microscopy, and residual DNA quantified spectrophotometrically and compared with controls. Airway compliance was evaluated by endotracheal intubation and mechanical ventilation to simulate physiological breathing-induced stretch. Structural integrity was evaluated by bronchoscopy and biomechanical stress/strain analysis by measuring passive tensile strength, all compared with controls. Decellularized lungs and trachea lacked intracellular components but retained specific collagen fibers and elastin. Quantitative DNA analysis demonstrated a significant reduction of DNA compared with controls (32.8 ± 12.4 μg DNA/mg tissue vs. 179.7 ± 35.8 μg DNA/mg tissue, P < 0.05). Lungs and trachea decellularized by our perfusion protocol demonstrated increased airway compliance but preserved biomechanical integrity as compared with native tissue. Whole porcine lungs-tracheae can be successfully decellularized to create an acellular scaffold that preserves extracellular matrix and retains structral integrity and three-dimensional architecture to provide a bioartifical platform for respiratory tissue engineering.

  18. Ventilation/perfusion lung scan probability category distributions in university and community hospitals.

    PubMed

    Lowe, V J; Bullard, A G; Coleman, R E

    1995-12-01

    The criteria used in the Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) study for the interpretation of ventilation/perfusion scans are widely used and the probability of pulmonary embolism is determined from these criteria. The prevalence of pulmonary embolism in the PIOPED study was 33%. To investigate the similarity of patient populations who have ventilation/perfusion scans at one of the medical centers that participated in the PIOPED study and a small community hospital, the authors evaluated the probability category distributions of lung scans at the two institutions. They retrospectively interpreted 54 and 49 ventilation/perfusion lung scans selected from January, 1991, to June, 1992, at Duke University Medical Center and at Central Carolina Hospital, respectively. Studies were interpreted according to the PIOPED criteria. The percentage of studies assigned to each category at Duke University Medical Center and Central Carolina Hospital were 17% and 27% normal or very low probability, 31% and 59% low probability, 39% and 10% intermediate probability, and 13% and 4% high probability, respectively. The different distribution of probability categories between university and community hospitals suggests that the prevalence of disease may also be different. The post-test probability of pulmonary embolism is related to the prevalence of disease and the sensitivity and specificity of the ventilation/perfusion scan. Because these variables may differ in community hospital settings, the post-test probability of pulmonary embolism as determined by data from the PIOPED study should only be used in institutions with similar populations. Clinical management based upon the results of the PIOPED study may not be applicable to patients who have ventilation/perfusion scans performed in a community hospital.

  19. Early results in transplantation of initially rejected donor lungs after ex vivo lung perfusion: a case-control study.

    PubMed

    Wallinder, Andreas; Ricksten, Sven-Erik; Silverborn, Martin; Hansson, Christoffer; Riise, Gerdt C; Liden, Hans; Jeppsson, Anders; Dellgren, Göran

    2014-01-01

    An increasing number of studies have shown that ex vivo lung perfusion (EVLP) is safe and that rejected donor lungs can be resuscitated and used for lung transplantation (LTx). Early clinical outcomes in patients transplanted with reconditioned lungs at our centre were reviewed and compared with those of contemporary non-EVLP controls. During 18 months starting January 2011, 11 pairs of donor lungs initially deemed unsuitable for transplantation underwent EVLP. Haemodynamic (pulmonary flow, vascular resistance and artery pressure) and respiratory (peak airway pressure and compliance) parameters were analysed during evaluation. Lungs that improved (n = 11) to meet International Society of Heart and Lung Transplantation criteria were transplanted and compared with patients transplanted with non-EVLP lungs (n = 47) during the same time period. Donor lungs were initially rejected due to either inferior PaO2/FiO2 ratio (n = 9), bilateral infiltrate on chest X-ray (n = 1) or ongoing extra corporeal membrane oxygenation (n = 1). The donor lungs improved from a mean PaO2/FiO2 ratio of 27.9 kPa in the donor to a mean of 59.6 kPa at the end of the EVLP (median improvement 28.4 kPa, range 21.0-50.7 kPa). Two single lungs were deemed unsuitable and not used for LTx. Eleven recipients from the regular waiting list underwent either single (n = 3) LTx or double (n = 8) LTx with EVLP-treated lungs. The median time to extubation (12 (range, 3-912) vs 6 (range, 2-1296) h) and median intensive care unit (ICU) stay (152 (range, 40-625) vs 48 (range, 22-1632) h) were longer in the EVLP group (P = 0.05 and P = 0.01, respectively). There were no differences in length of hospital stay (median 28 (range 25-93) vs 28 (18-209), P = 0.21). Two patients in the EVLP group and 6 in the control group had primary graft dysfunction >Grade 1 at 72 h postoperatively. Three patients in the control group died before discharge. All recipients of EVLP lungs were discharged alive from hospital. The use of

  20. Ex Vivo Lung Perfusion in the Rat: Detailed Procedure and Videos

    PubMed Central

    Lonati, Caterina; Brambilla, Daniela; Rapido, Francesca; Valenza, Franco; Gatti, Stefano

    2016-01-01

    Ex vivo lung perfusion (EVLP) is a promising procedure for evaluation, reconditioning, and treatment of marginal lungs before transplantation. Small animal models can contribute to improve clinical development of this technique and represent a substantial platform for bio-molecular investigations. However, to accomplish this purpose, EVLP models must sustain a prolonged reperfusion without pharmacological interventions. Currently available protocols only partly satisfy this need. The aim of the present research was accomplishment and optimization of a reproducible model for a protracted rat EVLP in the absence of anti-inflammatory treatment. A 180 min, uninjured and untreated perfusion was achieved through a stepwise implementation of the protocol. Flow rate, temperature, and tidal volume were gradually increased during the initial reperfusion phase to reduce hemodynamic and oxidative stress. Low flow rate combined with open atrium and protective ventilation strategy were applied to prevent lung damage. The videos enclosed show management of the most critical technical steps. The stability and reproducibility of the present procedure were confirmed by lung function evaluation and edema assessment. The meticulous description of the protocol provided in this paper can enable other laboratories to reproduce it effortlessly, supporting research in the EVLP field. PMID:27936178

  1. Ex vivo rehabilitation of non-heart-beating donor lungs in preclinical porcine model: delayed perfusion results in superior lung function.

    PubMed

    Mulloy, Daniel P; Stone, Matthew L; Crosby, Ivan K; Lapar, Damien J; Sharma, Ashish K; Webb, David V; Lau, Christine L; Laubach, Victor E; Kron, Irving L

    2012-11-01

    Ex vivo lung perfusion (EVLP) is a promising modality for the evaluation and treatment of marginal donor lungs. The optimal timing of EVLP initiation and the potential for rehabilitation of donor lungs with extended warm ischemic times is unknown. The present study compared the efficacy of different treatment strategies for uncontrolled non-heart-beating donor lungs. Mature swine underwent hypoxic arrest, followed by 60 minutes of no-touch warm ischemia. The lungs were harvested and flushed with 4°C Perfadex. Three groups (n = 5/group) were stratified according to the preservation method: cold static preservation (CSP; 4 hours of 4°C storage), immediate EVLP (I-EVLP: 4 hours EVLP at 37°C), and delayed EVLP (D-EVLP; 4 hours of CSP followed by 4 hours of EVLP). The EVLP groups were perfused with Steen solution supplemented with heparin, methylprednisolone, cefazolin, and an adenosine 2A receptor agonist. The lungs then underwent allotransplantation and 4 hours of recipient reperfusion before allograft assessment for resultant ischemia-reperfusion injury. The donor blood oxygenation (partial pressure of oxygen/fraction of inspired oxygen ratio) before death was not different between the groups. The oxygenation after transplantation was significantly greater in the D-EVLP group than in the I-EVLP or CSP groups. The mean airway pressure, pulmonary artery pressure, and expression of interleukin-8, interleukin-1β, and tumor necrosis factor-α were all significantly reduced in the D-EVLP group. Post-transplant oxygenation exceeded the acceptable clinical levels only in the D-EVLP group. Uncontrolled non-heart-beating donor lungs with extended warm ischemia can be reconditioned for successful transplantation. The combination of CSP and EVLP in the D-EVLP group was necessary to obtain optimal post-transplant function. This finding, if confirmed clinically, will allow expanded use of nonheart-beating donor lungs. Copyright © 2012 The American Association for Thoracic

  2. Clinical application of dual-source CT in the evaluation of patients with lung cancer: correlation with perfusion scintigraphy and pulmonary function tests.

    PubMed

    Fraioli, F; Serra, G; Liberali, S; Fiorelli, A; Liparulo, V; Zaccagna, F; Ciccariello, G; Catalano, C; Passariello, R

    2011-09-01

    This study was done to assess the diagnostic potential of dual-source computed tomography (DSCT) in the functional evaluation of lung cancer patients undergoing surgical resection. The CT data were compared with pulmonary perfusion scintigraphy and pulmonary function tests (PFTs). All patients were evaluated with DSCT, scintigraphy and PFTs. The DSCT scan protocol was as follows: two tubes (80 and 140 kV; Care Dose protocol); 70 cc of contrast material (5 cc/s); 5- to 6-s scan time; 0.6 mm collimation. After the automatic calculation of lung perfusion with DSCT and quantification of air volumes and emphysema with dedicated software applications, the perfusional CT studies were compared with scintigraphy using a visual score for perfusion defects; CT air volumes and emphysema were compared with PFTs. The values of accuracy, sensitivity, specificity and positive (PPV) and negative (NPV) predictive values of DSCT compared with perfusion scintigraphy as the reference standard were: 0.88, 0.84, 0.90, 0.93 and 0.88, respectively. The McNemar test did not identify significant differences either between the two imaging techniques (p=0.07) or between CT and PFTs (p=0.09). DSCT is a robust and promising technique that provides important and accurate information on lung function.

  3. Increasing the accuracy of lung perfusion scintigraphy in children with bidirectional Glenn circulation.

    PubMed

    Fukuda, Yutaka; Momoi, Nobuo; Mitomo, Masaki; Aoyagi, Yoshimichi; Endo, Kisei; Matsumoto, Ayumi; Hosoya, Mitsuaki

    2010-12-01

    In children who have undergone a bidirectional Glenn procedure without antegrade or additional pulmonary blood flow, we have often noted a discrepancy between apparent lung perfusion on scintigraphy and superior vena cava angiography when evaluating right and left pulmonary blood flow. We found a tendency for radionuclide, tracer 99mTc-MAA, when administered through a single upper extremity vein, to preferentially accumulate in the ipsilateral lung. In the present study, we examined whether the ratio of right-to-left pulmonary flow varied when 99mTc-MAA was administered via either the right upper or the left upper extremity vein. We studied six children (median age 1.3 ± 0.23 years) who underwent a bidirectional Glenn before total cavopulmonary connection. Five children who underwent biventricular repair served as a control. Perfusion scintigraphy using 99mTc-labeled macroaggregated albumin (99mTc-MAA) was performed in all children. First, we injected radionuclide via the right upper extremity and calculated the pulmonary accumulation in both lungs (R-image). Second, we injected the same dose of radionuclide via the left upper extremity and calculated the pulmonary accumulation (B-image), which represented the resulting administration via both upper extremities. The lung accumulation that resulted from radionuclide administration via the left upper extremity (L-image) was determined by subtracting the R-image from the B-image. We evaluated the right-to-total pulmonary blood flow ratio (radionuclide accumulation in right lung / radionuclide accumulation in both lungs) in the R-, L- and B-images. The right-to-total pulmonary blood flow ratios in the R-, L- and B-images were 815 ± 15.3%, 39.8 ± 11.7% and 61.3 ± 11.8%, respectively, and there were significant differences among the three images (P < 0.01). On the other hand, in the control group, the right-to-total pulmonary blood flow ratios in the R-, L- and B-images were 59.3 ± 22.4%, 57.8 ± 26.4% and 58.8

  4. Activation of rho is involved in the mechanism of hydrogen-peroxide-induced lung edema in isolated perfused rabbit lung.

    PubMed

    Chiba, Y; Ishii, Y; Kitamura, S; Sugiyama, Y

    2001-09-01

    Acute lung injury is attributed primarily to increased vascular permeability caused by reactive oxygen species derived from neutrophils, such as hydrogen peroxide (H2O2). Increased permeability is accompanied by the contraction and cytoskeleton reorganization of endothelial cells, resulting in intercellular gap formation. The Rho family of Ras-like GTPases is implicated in the regulation of the cytoskeleton and cell contraction. We examined the role of Rho in H2O2-induced pulmonary edema with the use of isolated perfused rabbit lungs. To our knowledge, this is the first study to examine the role of Rho in increased vascular permeability induced by H2O2 in perfused lungs. Vascular permeability was evaluated on the basis of the capillary filtration coefficient (Kfc, ml/min/cm H2O/100 g). We found that H2O2 (300 microM) increased lung weight, Kfc, and pulmonary capillary pressure. These effects of H2O2 were abolished by treatment with Y-27632 (50 microM), an inhibitor of the Rho effector p160 ROCK. In contrast, the muscular relaxant papaverine inhibited the H2O2-induced rise in pulmonary capillary pressure, but did not suppress the increases in lung weight and Kfc. These findings indicate that H2O2 causes pulmonary edema by elevating hydrostatic pressure and increasing vascular permeability. Y-27632 inhibited the formation of pulmonary edema by blocking both of these H2O2-induced effects. Our results suggest that Rho-related pathways have a part in the mechanism of H2O2-induced pulmonary edema. Copyright 2001 Academic Press.

  5. Vibration-response imaging versus quantitative perfusion scintigraphy in the selection of patients for lung-resection surgery.

    PubMed

    Comce, Fatma; Bingol, Zuleyha; Kiyan, Esen; Tanju, Serhan; Toker, Alper; Cagatay, Pembe; Ece, Turhan

    2011-12-01

    In patients being considered for lung-resection surgery, quantitative perfusion scintigraphy is used to predict postoperative lung function and guide the determination of lung-resection candidacy. Vibration-response imaging has been proposed as a noninvasive, radiation-free, and simpler method to predict postoperative lung function. We compared vibration-response imaging to quantitative perfusion scintigraphy for predicting postoperative FEV(1) and diffusing capacity of the lung for carbon monoxide (D(LCO)). We enrolled 35 candidates for lung resection. Twenty-five patients had preoperative FEV(1) and D(LCO) MEASUREMENTS: The vibration-response-imaging measurements showed strong correlation with the quantitative-perfusion-scintigraphy measurements of predicted postoperative FEV(1)% (r = 0.87, P < .001), predicted postoperative FEV(1) (r = 0.90, P < .001), and predicted postoperative D(LCO)% (r = 0.90, P < .001). There was a correlation between predicted postoperative FEV(1) (% and L) measured via quantitative perfusion scintigraphy and the actual postoperative FEV(1) (% and L) (r = 0.47, P = .048, r = 0.73, P < .001). There was no difference between the vibration-response-imaging measurements and the actual postoperative measurements of predicted postoperative FEV(1) (% and L). There was a correlation between predicted postoperative FEV(1) (% and L) measured via vibration-response imaging and actual postoperative FEV(1) (% and L) (r = 0.52, P = .044, r = 0.79, P < .001). The mean differences between the predicted and actual postoperative FEV(1) values were 49 mL with vibration-response imaging, versus 230 mL with quantitative perfusion scintigraphy. Neither the vibration-response imaging nor the quantitative perfusion scintigraphy predicted postoperative D(LCO)% values agreed with the actual postoperative D(LCO)% values. Vibration-response imaging may be a good alternative to quantitative perfusion scintigraphy in evaluating lung-resection candidacy.

  6. Effects of carbonic anhydrase inhibition on ventilation-perfusion matching in the dog lung.

    PubMed Central

    Swenson, E R; Robertson, H T; Hlastala, M P

    1993-01-01

    Lung carbonic anhydrase (CA) permits rapid pH responses when changes in regional ventilation or perfusion alter airway and alveolar PCO2. These pH changes affect airway and vascular resistances and lung compliance to optimize the balance of regional ventilation (VA) and perfusion (Q) in the lung. To test the hypothesis that these or other CA-dependent mechanisms contribute to VA/Q matching, we administered acetazolamide (25 mg/kg intravenously) to six anesthetized and paralyzed dogs and measured VA/Q relationships before and after CA inhibition by the multiple inert gas elimination technique. Four other groups of dogs were studied to control for possible confounding effects of time under anesthesia and nonselective CA inhibition by acetazolamide: (a) saline placebo as a control for duration of anesthesia, (b) 4% CO2 inhalation to mimic systemic CO2 retention, (c) 1 mg/kg benzolamide (a selective renal CA inhibitor) or 0.5 meq/kg HCl to mimic systemic metabolic acidosis, and (d) 500 mg/kg 4,4'-dinitrostilbene-2,2'-disulfonate (an inhibitor of red cell band 3 protein) to mimic the respiratory acidosis arising from an intracapillary block to rapid mobilization of plasma HCO3- in CO2 exchange. Acetazolamide increased VA/Q mismatch and reduced arterial PO2 measured at equilibrium but these did not occur in the control group. There was no deterioration in VA/Q matching when systemic respiratory acidosis produced either by CO2 inhalation or 4,4'-dinitrostilbene-2,2'-disulfonate or metabolic acidosis (benzolamide or HCl) were imposed to mimic the effects of acetazolamide apart from its inhibition of lung CA. These results support the concept that lung CA subserves VA/Q matching in the normal lung. Images PMID:8349809

  7. Meta-analysis of the independent and cumulative effects of multiple genetic modifications on pig lung xenograft performance during ex vivo perfusion with human blood.

    PubMed

    Harris, Donald G; Quinn, Kevin J; French, Beth M; Schwartz, Evan; Kang, Elizabeth; Dahi, Siamak; Phelps, Carol J; Ayares, David L; Burdorf, Lars; Azimzadeh, Agnes M; Pierson, Richard N

    2015-01-01

    Genetically modified pigs are a promising potential source of lung xenografts. Ex vivo xenoperfusion is an effective platform for testing the effect of new modifications, but typical experiments are limited by testing of a single genetic intervention and small sample sizes. The purpose of this study was to analyze the individual and aggregate effects of donor genetic modifications on porcine lung xenograft survival and injury in an extensive pig lung xenoperfusion series. Data from 157 porcine lung xenoperfusion experiments using otherwise unmodified heparinized human blood were aggregated as either continuous or dichotomous variables. Lungs were wild type in 17 perfusions (11% of the study group), while 31 lungs (20% of the study group) had one genetic modification, 40 lungs (39%) had 2, and 47 lungs (30%) had 3 or more modifications. The primary endpoint was functional lung survival to 4 h of perfusion. Secondary analyses evaluated previously identified markers associated with known lung xenograft injury mechanisms. In addition to comparison among all xenografts grouped by survival status, a subgroup analysis was performed of lungs incorporating the GalTKO.hCD46 genotype. Each increase in the number of genetic modifications was associated with additional prolongation of lung xenograft survival. Lungs that exhibited survival to 4 h generally had reduced platelet activation and thrombin generation. GalTKO and the expression of hCD46, HO-1, hCD55, or hEPCR were associated with improved survival. hTBM, HLA-E, and hCD39 were associated with no significant effect on the primary outcome. This meta-analysis of an extensive lung xenotransplantation series demonstrates that increasing the number of genetic modifications targeting known xenogeneic lung injury mechanisms is associated with incremental improvements in lung survival. While more detailed mechanistic studies are needed to explore the relationship between gene expression and pathway-specific injury and explore

  8. Detection of reactive oxygen species in isolated, perfused lungs by electron spin resonance spectroscopy

    PubMed Central

    Weissmann, Norbert; Kuzkaya, Nermin; Fuchs, Beate; Tiyerili, Vedat; Schäfer, Rolf U; Schütte, Hartwig; Ghofrani, Hossein A; Schermuly, Ralph T; Schudt, Christian; Sydykov, Akylbek; Egemnazarow, Bakytbek; Seeger, Werner; Grimminger, Friedrich

    2005-01-01

    Background The sources and measurement of reactive oxygen species (ROS) in intact organs are largely unresolved. This may be related to methodological problems associated with the techniques currently employed for ROS detection. Electron spin resonance (ESR) with spin trapping is a specific method for ROS detection, and may address some these technical problems. Methods We have established a protocol for the measurement of intravascular ROS release from isolated buffer-perfused and ventilated rabbit and mouse lungs, combining lung perfusion with the spin probe l-hydroxy-3-carboxy-2,2,5,5-tetramethylpyrrolidine (CPH) and ESR spectroscopy. We then employed this technique to characterize hypoxia-dependent ROS release, with specific attention paid to NADPH oxidase-dependent superoxide formation as a possible vasoconstrictor pathway. Results While perfusing lungs with CPH over a range of inspired oxygen concentrations (1–21 %), the rate of CP• formation exhibited an oxygen-dependence, with a minimum at 2.5 % O2. Addition of superoxide dismutase (SOD) to the buffer fluid illustrated that a minor proportion of this intravascular ROS leak was attributable to superoxide. Stimulation of the lungs by injection of phorbol-12-myristate-13-acetate (PMA) into the pulmonary artery caused a rapid increase in CP• formation, concomitant with pulmonary vasoconstriction. Both the PMA-induced CPH oxidation and the vasoconstrictor response were largely suppressed by SOD. When the PMA challenge was performed at different oxygen concentrations, maximum superoxide liberation and pulmonary vasoconstriction occurred at 5 % O2. Using a NADPH oxidase inhibitor and NADPH-oxidase deficient mice, we illustrated that the PMA-induced superoxide release was attributable to the stimulation of NADPH oxidases. Conclusion The perfusion of isolated lungs with CPH is suitable for detection of intravascular ROS release by ESR spectroscopy. We employed this technique to demonstrate that 1) PMA

  9. Correlation between the clinical pretest probability score and the lung ventilation and perfusion scan probability

    PubMed Central

    Bhoobalan, Shanmugasundaram; Chakravartty, Riddhika; Dolbear, Gill; Al-Janabi, Mazin

    2013-01-01

    Purpose: Aim of the study was to determine the accuracy of the clinical pretest probability (PTP) score and its association with lung ventilation and perfusion (VQ) scan. Materials and Methods: A retrospective analysis of 510 patients who had a lung VQ scan between 2008 and 2010 were included in the study. Out of 510 studies, the number of normal, low, and high probability VQ scans were 155 (30%), 289 (57%), and 55 (11%), respectively. Results: A total of 103 patients underwent computed tomography pulmonary angiography (CTPA) scan in which 21 (20%) had a positive scan, 81 (79%) had a negative scan and one (1%) had an equivocal result. The rate of PE in the normal, low-probability, and high-probability scan categories were: 2 (9.5%), 10 (47.5%), and 9 (43%) respectively. A very low correlation (Pearson correlation coefficient r = 0.20) between the clinical PTP score and lung VQ scan. The area under the curve (AUC) of the clinical PTP score was 52% when compared with the CTPA results. However, the accuracy of lung VQ scan was better (AUC = 74%) when compared with CTPA scan. Conclusion: The clinical PTP score is unreliable on its own; however, it may still aid in the interpretation of lung VQ scan. The accuracy of the lung VQ scan was better in the assessment of underlying pulmonary embolism (PE). PMID:24379532

  10. Effect of perfusate hematocrit on urea permeability-surface area in isolated dog lung

    SciTech Connect

    Parker, R.E.; Roselli, R.J.; Haselton, F.R.; Harris, T.R.

    1986-10-01

    Seven dog lower left lung lobes were statically inflated and perfused at a constant rate for each lobe with a perfusate in which the hematocrit was altered over a wide range. The permeability-surface area of urea was calculated from multiple indicator dilution curves using two separate injectates for each hematocrit level. One injectate contained only /sup 125/I-albumin as the vascular reference tracer and the other contained both /sup 51/Cr-erythrocytes and /sup 125/I-albumin as the vascular reference tracers; both contained (/sup 14/C)urea as the permeating tracer. The results strongly indicate that the phenomenon of erythrocyte trapping of urea does not affect the calculation of urea permeability-surface area product provided the appropriate albumin-erythrocyte composite reference tracer is utilized in its calculation.

  11. Bronchodilator Inhalation During Ex Vivo Lung Perfusion Improves Posttransplant Graft Function After Warm Ischemia.

    PubMed

    Hijiya, Kyoko; Chen-Yoshikawa, Toyofumi F; Kondo, Takeshi; Motoyama, Hideki; Ohsumi, Akihiro; Nakajima, Daisuke; Sakamoto, Jin; Ohata, Keiji; Takahashi, Mamoru; Tanaka, Satona; Miyamoto, Ei; Aoyama, Akihiro; Date, Hiroshi

    2017-02-01

    We hypothesized that an injured lung graft from donation after cardiac death donors could be reconditioned before transplantation using an ex vivo lung perfusion (EVLP) system and ventilation with high-dose short-acting β2-adrenergic receptor agonists. Cardiac arrest was induced in a canine model by intravenous potassium chloride injection. Lungs were randomly assigned to two groups after 150 minutes of warm ischemia: inhalation of 1,400 μg of procaterol (BETA group, n = 5) or control group receiving solvent (CON group, n = 5) during EVLP. Left lungs were transplanted after 120 minutes of EVLP. Functional variables, tissue adenosine 5'-triphosphate levels, and tissue cyclic adenosine monophosphate levels were measured 240 minutes after transplantation. Physiologic pulmonary function was similar at the end of EVLP in both groups. However, significantly better graft oxygenation, dynamic pulmonary compliance, and reduced pulmonary vascular resistance were observed in the BETA group than in the CON group 240 minutes after transplantation. No severe adverse effects were observed after lung transplantation in the BETA group. Lung tissue adenosine 5'-triphosphate levels and cyclic adenosine monophosphate levels were significantly higher in the BETA group than in the CON group at the end of EVLP and at 240 minutes after transplantation. High-dose nebulized procaterol during EVLP ameliorated lung graft dysfunction at the early posttransplantation period without severe adverse effects. These data suggest that lung reconditioning with procaterol ventilation during EVLP improves lung graft function after transplantation. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  12. Influence of pulmonary regurgitation inequality on differential perfusion of the lungs in tetralogy of Fallot after repair: a phase-contrast magnetic resonance imaging and perfusion scintigraphy study.

    PubMed

    Wu, Ming-Ting; Huang, Yi-Luan; Hsieh, Kai-Sheng; Huang, Ju-Tung; Peng, Nan-Jing; Pan, Jun-Yen; Huang, Jer-Shyung; Yang, Tsung-Lung

    2007-05-08

    The purpose of this study was to evaluate the influence of pulmonary regurgitation inequality on differential perfusion of the lungs in tetralogy of Fallot (TOF) after repair. Asymmetry of lung perfusion is one of the best predictors of outcome in TOF after repair. A recent phase-contrast magnetic resonance imaging (PC-MRI) study found prominent regurgitation inequality between the bilateral pulmonary arteries in TOF after repair. Forty-three TOF post-repair patients (median age = 51 months, 31 men) received PC-MRI and 99mTc-labeled macroaggregates of albumin perfusion scintigraphy (PS) in the same day. We took PC-MRI measurements of forward flow volume (FFV), backward flow volume (BFV), and net flow volume (NFV) (NFV = FFV - BFV) and regurgitation fraction (RF) (RF = BFV/FFV) at the left and right pulmonary arteries (LPA and RPA). The differential perfusion of the left lung (L%) (L% = left lung/left + right lung) as calculated by NFV ratio, by FFV ratio of PC-MRI, and by PS were compared. The discrepancy between L% by NFV versus L% by PS was affected by the severity of RF of LPA (r = -0.51, p = 0.001); agreement between L% by NFV versus L% by PS was good (intraclass correlation coefficient [Ri] = 0.87) if RF of LPA <0.4 (n = 23) but downgraded (Ri = 0.51) and underestimated the L% (median of error = -14%, range = -25.3% to 5.5%) if RF of LPA > or =0.4 (n = 20). In contrast, agreement between L% by FFV versus L% by PS was high and unaffected by RF of LPA (Ri = 0.94, 0.92, respectively). While integrating PC-MRI of pulmonary artery as a comprehensive MRI evaluation of TOF after repair, conventional NFV ratio method tended to underestimate the left lung perfusion and may lead to unnecessary intervention. The FFV ratio method should be used for precise assessment of differential lung perfusion.

  13. Lung Radiofrequency Ablation: In Vivo Experimental Study with Low-Perfusion-Rate Multitined Electrodes

    SciTech Connect

    Crocetti, Laura Lencioni, Riccardo; Bozzi, Elena; Sbrana, Alberto; Bartolozzi, Carlo

    2008-05-15

    The purpose of this study was to investigate the feasibility and safety of lung radiofrequency (RF) ablation by using low-perfusion-rate, expandable, multitined electrodes in an in vivo animal model. Ten New Zealand White rabbits underwent RF ablation using low-perfusion-rate, expandable, multitined electrodes (Starburst Talon; RITA Medical Systems, Mountain View, CA) and a 200-W RF generator. The electrode was positioned under fluoroscopy guidance and a single percutaneous RF ablation was performed. Saline perfusate was doped with nonionic iodinated contrast agent to render it visible on computed tomography (CT). The pump infused the saline doped with contrast agent into the lateral tines at a rate of 0.1ml/min. The planned ablation was of 3 min, with the hooks deployed to 2 cm at a target temperature of 105{sup o}C. An immediate posttreatment CT scan documented the distribution of the doped saline and the presence of immediate complications. The animals were monitored for delayed complications and sacrificed within 72 h (n = 4), 2 weeks (n = 3), or 4 weeks (n = 3). Assessment of ablation zone and adjacent structures was done at autopsy. Major complications consisted of pneumothorax requiring drainage (n = 2) and skin burn (n = 1). Immediately after the procedure the area of ablation was depicted at CT as a round, well-demarcated area, homogeneously opacified by iodinated contrast medium (mean size, 2.3 {+-} 0.8 cm). The presence of a sharply demarcated area of coagulation necrosis (mean size, 2.1 {+-} 0.4 cm) without severe damage to adjacent structures was confirmed at autopsy. In one case, euthanized at 4 weeks, in whom pneumothorax and pleural effusion were depicted, pleural fibrinous adhesions were demonstrated at autopsy. In conclusion, lung RF ablation performed in an in vivo animal model using low-perfusion-rate, expandable, multitined electrodes is feasible and safe. No severe damage to adjacent structures was demonstrated.

  14. Effect of halothane on metabolism of 5-hydroxytryptamine by rat lungs perfused in situ.

    PubMed Central

    Watkins, C A; Wartell, S A; Rannels, D E

    1983-01-01

    The effect of halothane (2-bromo-2-chloro-1,1,1-trifluoroethane) on the uptake of 14C-labelled 5-hydroxytryptamine (5-HT) and its metabolism to 5-hydroxyindol-3-ylacetic acid (5-HIAA) was investigated in rat lungs perfused in situ. The rate of accumulation of 14C-labelled 5-HIAA in the tissue, monitored as an index of 5-HT metabolism, was linear with time, displayed saturation kinetics and remained stable for at least 180 min of perfusion. Exposure of the lungs to halothane (4%) for 60 min reversibly reduced production of 5-HIAA through an increase in the apparent Km for metabolism of the amine from 1.45 to 3.52 microM (P less than 0.001); the anaesthetic had no effect on the Vmax. of the process. The magnitude of the inhibition increased with time of exposure to the anaesthetic. Halothane exposure did not alter the distribution of [3H]sorbitol or [14C]5-HT, pulmonary vascular resistance, levels of ATP or the kinetics of amino acid transport in the tissue. Inhibition of protein synthesis by cycloheximide did not mimic the effect of the anaesthetic. These observations, together with those made in lungs exposed to inhibitors of 5-HT uptake and metabolism, were consistent with a halothane-mediated inhibition of 5-HT uptake, which did not appear to involve non-specific changes in membrane permeability. PMID:6847641

  15. [Examination of R-L shunt ratio mensuration using dynamic images in lung perfusion scintigraphy].

    PubMed

    Ichikawa, Hajime; Yamada, Sayaka; Yoshioka, Chiho; Tamaoki, Toyoshi; Miura, Syunichi; Suzuki, Motoki; Makino, Tetsuzou

    2008-05-20

    We examined a method of quantitative analysis that used dynamic and static images to measure the Right-left (R-L) shunt ratio in lung perfusion scintigraphy. A total of 18 patients suspected of having R-L shunt brought on by congenital heart disease were referred for lung perfusion scintigraphy from November 2005 to February 2007 at our hospital. We acquired anterior dynamic images, set ROIs in all fields of view, and measured the highest count. We acquired anterior and posterior static images of the chest and measured lung counts. We considered the highest count on dynamic images to be the total injection dose per one second, normalized the acquisition time of static images, and calculated the R-L shunt ratio. We weighed the measurement results of the R-L shunt ratio obtained by the dynamic method against that of the whole-body method by t-test and the least-squares method. When we used a posterior static image in the dynamic method, we found that the coefficient of correlation (r) was 0.9831. The result of the t-test was that there was no significant difference at a level of significance of 1%. We think the use of the dynamic method is possible in R-L shunt ratio measurement and can shorten the examination time.

  16. The effects of hydrogen gas inhalation during ex vivo lung perfusion on donor lungs obtained after cardiac death.

    PubMed

    Haam, Seokjin; Lee, Sungsoo; Paik, Hyo Chae; Park, Moo Suk; Song, Joo Han; Lim, Beom Jin; Nakao, Atsunori

    2015-10-01

    Lung transplantation is a well-established treatment of end-stage lung disease; however, it is limited by a shortage of donor lungs. To overcome this problem, donation after cardiac death (DCD) and ex vivo lung perfusion (EVLP) are being widely investigated. In this study, the effect of hydrogen gas, a known antioxidant, was investigated on a DCD lung model during EVLP. Ten pigs were randomized into either a control (n = 5) or a hydrogen group (n = 5). After fibrillation by electric shock, no further treatment was administered in order to induce warm ischaemic injury for 1 h. The lungs were then procured, followed by 4 h of EVLP. During EVLP, the lungs were ventilated with room air in the control group, and with 2% hydrogen gas in the hydrogen group. Oxygen capacity (OC), pulmonary vascular resistance (PVR) and peak airway pressure (PAP) were measured every hour, and the expressions of interleukin-1 beta (IL-1β), IL-6 (IL-6), IL-8 (IL-8) and tumour necrosis factor-alpha (TNF-α) were evaluated in lung tissue after EVLP. Pathological evaluations were performed using lung injury severity (LIS) scores and the wet/dry ratio was also measured. The OC in the hydrogen group was higher than in the control group, but the difference was not statistically significant (P = 0.0862). PVR (P = 0.0111) and PAP (P = 0.0189) were statistically significantly lower in the hydrogen group. Compared with the control group, the hydrogen group had a statistically significantly lower expression of IL-1β (P = 0.0317), IL-6 (P = 0.0159), IL-8 (P = 0.0195) and TNF-α (P = 0.0159). The LIS scores (P = 0.0358) and wet/dry ratios (P = 0.040) were also significantly lower in the hydrogen group. Hydrogen gas inhalation during EVLP improved the function of DCD lungs, which may increase the utilization of DCD lungs. © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

  17. Donation After Circulatory Death Lungs Transplantable Up to Six Hours After Ex Vivo Lung Perfusion.

    PubMed

    Charles, Eric J; Huerter, Mary E; Wagner, Cynthia E; Sharma, Ashish K; Zhao, Yunge; Stoler, Mark H; Mehaffey, J Hunter; Isbell, James M; Lau, Christine L; Tribble, Curtis G; Laubach, Victor E; Kron, Irving L

    2016-12-01

    Despite the critical need for donor lungs, logistic and geographic barriers hinder lung utilization. We hypothesized that lungs donated after circulatory death subjected to 6 hours of cold preservation after ex vivo lung perfusion (EVLP) would have similar outcomes after transplantation as lungs transplanted immediately after EVLP, and that both would perform superiorly compared with lungs transplanted immediately after procurement. Donor porcine lungs were procured after circulatory death and 15 minutes of warm ischemia. Three groups (n = 5 per group) were randomized: immediate left lung transplantation (Immediate group), EVLP for 4 hours followed by transplantation (EVLP group), or EVLP for 4 hours followed by 6 hours of cold preservation followed by transplantation (EVLP+Cold group). Lungs were reperfused for 2 hours before obtaining pulmonary vein samples for partial pressure of oxygen/fraction of inspired oxygen ratio calculations, airway pressures for compliance measurements, and wet/dry weight ratios. The partial pressure of oxygen/fraction of inspired oxygen ratios in the EVLP and EVLP+Cold groups were significantly improved compared with those in the Immediate group (429.7 ± 51.8 and 436.7 ± 48.2 versus 117.4 ± 22.9 mm Hg, respectively). In addition, dynamic compliance was significantly improved in the EVLP and EVLP+Cold groups compared with immediate group (26.2 ± 4.2 and 27.9 ± 3.5 versus 11.1 ± 2.4 mL/cmH2O, respectively). There were no differences in oxygenation capacity or dynamic compliance between the EVLP and EVLP+Cold groups. Inflammatory cytokine levels were significantly lower in the EVLP and EVLP+Cold groups. Lungs donated after circulatory death can be successfully transplanted as much as 6 hours after EVLP. Cold preservation of lungs after ex vivo assessment and rehabilitation may improve organ allocation, even to distant recipients, without compromising allograft function. Copyright © 2016 The Society of Thoracic Surgeons

  18. 12-tetradecanoyl-phorbol-13-acetate (PMA) produces injury to isolated rat lungs in the presence and absence of perfused neutrophils

    SciTech Connect

    Carpenter, L.J.; Roth, R.A.

    1986-03-01

    PMA produced injury to isolated, perfused rat lungs when eutrophils were added to or omitted from the buffer/albumin perfusion medium. When a high dose of PMA (57 ng/ml) was added to medium devoid of added neutrophils, perfusion pressure and lung weight increased. Together, superoxide dismutase (500 U/ml) and catalase (400 U/ml) had no effect on the increases in lung weight or perfusion pressure. However, papaverine (0.5 mM) prevented both the increase in perfusion pressure and fluid accumulation. When a concentration of PMA (14 ng/ml) that did not by itself cause lungs to accumulate fluid was added to perfusion medium containing neutrophils (1 x 10/sup 8/), perfusion pressures increased and lungs accumulated fluid. This concentration of PMA stimulated neutrophils (1 x 10/sup 8/) to release superoxide. Addition of superoxide dismutase (500 U/ml) and catalase (400 U/ml) to this medium prevented the increase in lung weight, but not the increase in perfusion pressure. Papaverine (0.5 mM) attenuated the increase in perfusion pressure and prevented fluid accumulation in these lungs. In summary, high concentrations of PMA produce lung injury which is independent of oxygen radicals; at lower concentrations it produces injury which is neutrophil-dependent and mediated by oxygen radicals.

  19. Implementation and evaluation of a new workflow for registration and segmentation of pulmonary MRI data for regional lung perfusion assessment.

    PubMed

    Böttger, T; Grunewald, K; Schöbinger, M; Fink, C; Risse, F; Kauczor, H U; Meinzer, H P; Wolf, Ivo

    2007-03-07

    Recently it has been shown that regional lung perfusion can be assessed using time-resolved contrast-enhanced magnetic resonance (MR) imaging. Quantification of the perfusion images has been attempted, based on definition of small regions of interest (ROIs). Use of complete lung segmentations instead of ROIs could possibly increase quantification accuracy. Due to the low signal-to-noise ratio, automatic segmentation algorithms cannot be applied. On the other hand, manual segmentation of the lung tissue is very time consuming and can become inaccurate, as the borders of the lung to adjacent tissues are not always clearly visible. We propose a new workflow for semi-automatic segmentation of the lung from additionally acquired morphological HASTE MR images. First the lung is delineated semi-automatically in the HASTE image. Next the HASTE image is automatically registered with the perfusion images. Finally, the transformation resulting from the registration is used to align the lung segmentation from the morphological dataset with the perfusion images. We evaluated rigid, affine and locally elastic transformations, suitable optimizers and different implementations of mutual information (MI) metrics to determine the best possible registration algorithm. We located the shortcomings of the registration procedure and under which conditions automatic registration will succeed or fail. Segmentation results were evaluated using overlap and distance measures. Integration of the new workflow reduces the time needed for post-processing of the data, simplifies the perfusion quantification and reduces interobserver variability in the segmentation process. In addition, the matched morphological data set can be used to identify morphologic changes as the source for the perfusion abnormalities.

  20. Liquid flow across the epithelium of the artificially perfused lung of fetal and postnatal sheep.

    PubMed Central

    Ramsden, C A; Markiewicz, M; Walters, D V; Gabella, G; Parker, K A; Barker, P M; Neil, H L

    1992-01-01

    1. The lungs of five fetal (133-140 days gestation) and thirty-four postnatal (2-240 days) sheep were artificially perfused in situ with warmed and oxygenated sheep blood. In postnatal animals the airspace of the lung was filled with liquid similar in composition to fetal lung liquid. In fetal and postnatal animals luminal liquid volume was measured by the impermeant tracer technique. 2. Under resting conditions the pulmonary epithelium of fetal animals secreted liquid at a mean (+/- S.E.M.) rate of 2.0 (+/- 0.4) ml (kg body weight)-1 h-1, those of postnantal animals absorbed liquid at -1.8 (+/- 0.2) ml (kg body weight)-1 h-1. 3. Addition of 2,4-dinitrophenol to achieve a concentration of 1.5 x 10(-3) M in the perfusing blood in postnatal animals caused complete cessation of liquid absorption. 4. Light and electron microscopic examination of the lung after periods of up to 6 h of artificial perfusion showed no evidence of epithelial damage. From 3 h onwards, liquid accumulation was evident in the perivascular spaces. 5. Addition of adrenaline to the perfusate in fetal animals caused absorption of liquid to occur at a mean rate of -2.9 (+/- 1.3) ml (kg body weight)-1 h-1. In postnatal animals adrenaline caused the rate of liquid absorption to increase from a mean rate of -1.4 (+/- 0.2) to -2.2 (+/- 0.3) ml (kg body weight)-1 h-1. 6. In the fetus addition of amiloride (0.8 x 10(-4) M) to the luminal fluid blocked adrenaline-induced liquid absorption and caused secretion to occur at 1.3 (+/- 0.3) ml (kg body weight)-1 h-1. 7. In postnatal animals the response to amiloride was age dependent. In newborn lambs (2-14 days) amiloride blocked liquid absorption and caused secretion of liquid to occur in seven out of eight animals at a mean rate of 0.9 (+/- 0.3) ml (kg body weight)-1 h-1 (n = 8). In older animals (15-240 days) the characteristic response to amiloride was slowing of the rate of liquid absorption (mean rate of absorption,-0.2 (+/- 0.09) ml (kg body weight)-1 h

  1. 3D ECG- and respiratory-gated non-contrast-enhanced (CE) perfusion MRI for postoperative lung function prediction in non-small-cell lung cancer patients: A comparison with thin-section quantitative computed tomography, dynamic CE-perfusion MRI, and perfusion scan.

    PubMed

    Ohno, Yoshiharu; Seki, Shinichiro; Koyama, Hisanobu; Yoshikawa, Takeshi; Matsumoto, Sumiaki; Takenaka, Daisuke; Kassai, Yoshimori; Yui, Masao; Sugimura, Kazuro

    2015-08-01

    To compare predictive capabilities of non-contrast-enhanced (CE)- and dynamic CE-perfusion MRIs, thin-section multidetector computed tomography (CT) (MDCT), and perfusion scan for postoperative lung function in non-small cell lung cancer (NSCLC) patients. Sixty consecutive pathologically diagnosed NSCLC patients were included and prospectively underwent thin-section MDCT, non-CE-, and dynamic CE-perfusion MRIs and perfusion scan, and had their pre- and postoperative forced expiratory volume in one second (FEV1 ) measured. Postoperative percent FEV1 (po%FEV1 ) was then predicted from the fractional lung volume determined on semiquantitatively assessed non-CE- and dynamic CE-perfusion MRIs, from the functional lung volumes determined on quantitative CT, from the number of segments observed on qualitative CT, and from uptakes detected on perfusion scans within total and resected lungs. Predicted po%FEV1 s were then correlated with actual po%FEV1 s, which were %FEV1 s measured postoperatively. The limits of agreement were also determined. All predicted po%FEV1 s showed significant correlation (0.73 ≤ r ≤ 0.93, P < 0.0001) and limits of agreement with actual po%FEV1 (non-CE-perfusion MRI: 0.3 ± 10.0%, dynamic CE-perfusion MRI: 1.0 ± 10.8%, perfusion scan: 2.2 ± 14.1%, quantitative CT: 1.2 ± 9.0%, qualitative CT: 1.5 ± 10.2%). Non-CE-perfusion MRI may be able to predict postoperative lung function more accurately than qualitatively assessed MDCT and perfusion scan. © 2014 Wiley Periodicals, Inc.

  2. Antioxidants as Potential Therapeutics for Lung Fibrosis

    PubMed Central

    DAY, BRIAN J.

    2009-01-01

    Interstitial lung disease encompasses a large group of chronic lung disorders associated with excessive tissue remodeling, scarring, and fibrosis. The evidence of a redox imbalance in lung fibrosis is substantial, and the rationale for testing antioxidants as potential new therapeutics for lung fibrosis is appealing. Current animal models of lung fibrosis have clear involvement of ROS in their pathogenesis. New classes of antioxidant agents divided into catalytic antioxidant mimetics and antioxidant scavengers are being developed. The catalytic antioxidant class is based on endogenous antioxidant enzymes and includes the manganese-containing macrocyclics, porphyrins, salens, and the non–metal-containing nitroxides. The antioxidant scavenging class is based on endogenous antioxidant molecules and includes the vitamin E analogues, thiols, lazaroids, and polyphenolic agents. Numerous studies have shown oxidative stress to be associated with many interstitial lung diseases and that these agents are effective in attenuating fibroproliferative responses in the lung of animals and humans. PMID:17999627

  3. Changes in Functional Lung Regions During the Course of Radiation Therapy and Their Potential Impact on Lung Dosimetry for Non-Small Cell Lung Cancer

    SciTech Connect

    Meng, Xue; Frey, Kirk; Matuszak, Martha; Paul, Stanton; Ten Haken, Randall; Yu, Jinming; Kong, Feng-Ming

    2014-05-01

    Purpose: To study changes in functional activity on ventilation (V)/perfusion (Q) single-photon emission computed tomography (SPECT) during radiation therapy (RT) and explore the impact of such changes on lung dosimetry in patients with non-small cell lung cancer (NSCLC). Methods and Materials: Fifteen NSCLC patients with centrally located tumors were enrolled. All patients were treated with definitive RT dose of ≥60 Gy. V/Q SPECT-CT scans were performed prior to and after delivery of 45 Gy of fractionated RT. SPECT images were used to define temporarily dysfunctional regions of lung caused by tumor or other potentially reversible conditions as B3. The functional lung (FL) was defined on SPECT by 2 separate approaches: FL1, a threshold of 30% of the maximum uptake of the patient's lung; and FL2, FL1 plus B3 region. The impact of changes in FL between initiation of RT and delivery of 45 Gy on lung dosimetry were analyzed. Results: Fourteen patients (93%) had larger FL2 volumes than FL1 pre-RT (P<.001). Dysfunctional lung became functional in 11 patients (73%) on V SPECT and in 10 patients (67%) on Q SPECT. The dosimetric parameters generated from CT-based anatomical lung had significantly lower values in FL1 than FL2, with a median reduction in the volume of lung receiving a dose of at least 20 Gy (V{sub 20}) of 3%, 5.6%, and mean lung dose of 0.95 and 1.55 on V and Q SPECT respectively. Conclusions: Regional ventilation and perfusion function improve significantly during RT in centrally located NSCLC. Lung dosimetry values vary notably between different definitions of functional lung.

  4. Ex vivo lung perfusion to improve donor lung function and increase the number of organs available for transplantation.

    PubMed

    Valenza, Franco; Rosso, Lorenzo; Coppola, Silvia; Froio, Sara; Palleschi, Alessandro; Tosi, Davide; Mendogni, Paolo; Salice, Valentina; Ruggeri, Giulia M; Fumagalli, Jacopo; Villa, Alessandro; Nosotti, Mario; Santambrogio, Luigi; Gattinoni, Luciano

    2014-06-01

    This paper describes the initial clinical experience of ex vivo lung perfusion (EVLP) at the Fondazione Ca' Granda in Milan between January 2011 and May 2013. EVLP was considered if donor PaO2 /FiO2 was below 300 mmHg or if lung function was doubtful. Donors with massive lung contusion, aspiration, purulent secretions, pneumonia, or sepsis were excluded. EVLP was run with a low-flow, open atrium and low hematocrit technique. Thirty-five lung transplants from brain death donors were performed, seven of which after EVLP. EVLP donors were older (54 ± 9 years vs. 40 ± 15 years, EVLP versus Standard, P < 0.05), had lower PaO2 /FiO2 (264 ± 78 mmHg vs. 453 ± 119 mmHg, P < 0.05), and more chest X-ray abnormalities (P < 0.05). EVLP recipients were more often admitted to intensive care unit as urgent cases (57% vs. 18%, P = 0.05); lung allocation score at transplantation was higher (79 [40-84] vs. 39 [36-46], P < 0.05). After transplantation, primary graft dysfunction (PGD72 grade 3, 32% vs. 28%, EVLP versus Standard, P = 1), mortality at 30 days (0% vs. 0%, P = 1), and overall survival (71% vs. 86%, EVLP versus Standard P = 0.27) were not different between groups. EVLP enabled a 20% increase in available donor organs and resulted in successful transplants with lungs that would have otherwise been rejected (ClinicalTrials.gov number: NCT01967953).

  5. Ex vivo lung perfusion to improve donor lung function and increase the number of organs available for transplantation

    PubMed Central

    Valenza, Franco; Rosso, Lorenzo; Coppola, Silvia; Froio, Sara; Palleschi, Alessandro; Tosi, Davide; Mendogni, Paolo; Salice, Valentina; Ruggeri, Giulia M; Fumagalli, Jacopo; Villa, Alessandro; Nosotti, Mario; Santambrogio, Luigi; Gattinoni, Luciano

    2014-01-01

    This paper describes the initial clinical experience of ex vivo lung perfusion (EVLP) at the Fondazione Ca’ Granda in Milan between January 2011 and May 2013. EVLP was considered if donor PaO2/FiO2 was below 300 mmHg or if lung function was doubtful. Donors with massive lung contusion, aspiration, purulent secretions, pneumonia, or sepsis were excluded. EVLP was run with a low-flow, open atrium and low hematocrit technique. Thirty-five lung transplants from brain death donors were performed, seven of which after EVLP. EVLP donors were older (54 ± 9 years vs. 40 ± 15 years, EVLP versus Standard, P < 0.05), had lower PaO2/FiO2 (264 ± 78 mmHg vs. 453 ± 119 mmHg, P < 0.05), and more chest X-ray abnormalities (P < 0.05). EVLP recipients were more often admitted to intensive care unit as urgent cases (57% vs. 18%, P = 0.05); lung allocation score at transplantation was higher (79 [40–84] vs. 39 [36–46], P < 0.05). After transplantation, primary graft dysfunction (PGD72 grade 3, 32% vs. 28%, EVLP versus Standard, P = 1), mortality at 30 days (0% vs. 0%, P = 1), and overall survival (71% vs. 86%, EVLP versus Standard P = 0.27) were not different between groups. EVLP enabled a 20% increase in available donor organs and resulted in successful transplants with lungs that would have otherwise been rejected (ClinicalTrials.gov number: NCT01967953). PMID:24628890

  6. Normothermic Ex Vivo Lung Perfusion in Brain-dead Donors Reduces Inflammatory Cytokines and Toll-like Receptor Expression.

    PubMed

    Shafaghi, Shadi; Mortaz, Esmaeil; Abbasi Dezfuli, Azizollah; Godarzi, Hoda; Sheikhy, Kambiz; Ansari Aval, Zahra; Farzanegan, Behrooz; Emami, Habib; Hosseini-Baharanchi, Fatemeh Sadat; Najafizadeh, Katayoun

    2016-10-01

    Inflammatory responses and innate immunologic reactions play an important role in the respiratory system. Ex vivo lung perfusion (EVLP) is considered a novel method in the evaluation and reconditioning of donor lungs prior to transplantation. However, EVLP's effect on inflammatory and metabolic markers of human lung tissue is unknown.  This study investigated how the performance of EVLP on brain-dead (BD) donor lungs affects the production and release of inflammatory cytokines (IL-6, IL-8, and TNF-a), inflammatory cells and toll-like receptors (TLR) -2, 4. This study was conducted with an animal subject for qualification of EVLP team and then EVLP was performed on 4 human cases referred to Masih Daneshvari Hospital (Tehran,Iran), from May 2013 to July 2015. Two of these cases, who had acceptable lung function parameters, were enrolled in this study for immunologic investigations. Bronchoalveolar lavages (BAL) were taken before and after EVLP. Cytokines were quantitatively measured before lung retrieval, at the end of the lung removal, at the start of EVLP, and at the end of the each hour of EVLP. TLR expression was measured on the cells obtained by flow cytometry. TNF-a, IL-6 and IL-8 decreased in each stage of washing perfusate in both cases, and the level of cytokines in serum was in the normal range. Flow cytometry analysis revealed a decreasing expression of CD3, CD4/8, CD19, and CD16+56, as well as TLR-2 and TLR-4 in both cases. Intra-capillary pools of pro-inflammatory cytokines (IL-6, IL-8, and TNF-a) were determined to contribute to the lung injury during prolonged lung perfusion. This raises the possibility that EVLP donor lungs could be less immunogenic than standard lungs. However, to assess EVLP's effects on lung grafts and optimize recipient outcomes, further studies with a sufficient number of lungs are required.

  7. Improved diagnostic accuracy of lung perfusion imaging using Tc-99m MAA SPECT

    SciTech Connect

    O'Donnell, J.K.; Golish, J.A.; Go, R.T.; Risius, B.; Graor, R.A.; MacIntyre, W.J.; Feiglin, D.H.

    1984-01-01

    The addition of emission tomography (SPECT) to pulmonary perfusion imaging should improve diagnostic accuracy by detecting perfusion defects otherwise masked by superimposition of normal lung activity and by reducing problems with interpretation of defects that result from overlying soft tissue or pleural effusions. In order to examine the contribution of SPECT in the scintigraphic evaluation for pulmonary embolus (PE), the authors have obtained both planar and SPECT studies in 94 cases of suspected PE. All studies employed 3-4 mCi of Tc-99m MAA and standard six-view planar image acquisition. SPECT raw data of 64 images were then acquired over a 360 degree transaxial rotation with subsequent computer reconstruction. Xe-133 ventilation studies were performed when clinically indicated and tolerated by the patient. For 19 studies angiographic (AN) correlation was obtained within 24 hours. In 16/19 planar and SPECT both gave a high probability of PE but SPECT gave better segmental localization and showed better agreement with the number of defects seen at AN. In 3 indeterminate planar scans, 2 were low probability with SPECT and had negative AN. The third, a patient with Wegener's vasculitis, remained indeterminate with SPECT and had negative AN. Five patients with PE had repeat planar/SPECT/AN studies to evaluate response to treatment. SPECT correlated better with AN findings in each case. The authors conclude that SPECT perfusion imaging provides better anatomic accuracy for defects representing PE and is the non-invasive technique of choice for documenting response to therapy.

  8. Measurement of ventilation- and perfusion-mediated cooling during laser ablation in ex vivo human lung tumors.

    PubMed

    Vietze, Andrea; Koch, Franziska; Laskowski, Ulrich; Linder, Albert; Hosten, Norbert

    2011-11-01

    Perfusion-mediated tissue cooling has often been described in the literature for thermal ablation therapies of liver tumors. The objective of this study was to investigate the cooling effects of both perfusion and ventilation during laser ablation of lung malignancies. An ex vivo lung model was used to maintain near physiological conditions for the specimens. Fourteen human lung lobes containing only primary lung tumors (non-small cell lung cancer) were used. Laser ablation was carried out using a Nd:YAG laser with a wavelength of 1064 nm and laser fibers with 30 mm diffusing tips. Continuous invasive temperature measurement in 10 mm distance from the laser fiber was performed. Laser power was increased at 2 W increments starting at 10 W up to a maximum power of 12-20 W until a temperature plateau around 60 °C was reached at one sensor. Ventilation and perfusion were discontinued for 6 min each to assess their effects on temperature development. The experiments lead to 25 usable temperature profiles. A significant temperature increase was observed for both discontinued ventilation and perfusion. In 6 min without perfusion, the temperature rose about 5.5 °C (mean value, P<0.05); without ventilation it increased about 7.0 °C (mean value, P<0.05). Ventilation- and perfusion-mediated tissue cooling are significant influencing factors on temperature development during thermal ablation. They should be taken into account during the planning and preparation of minimally invasive lung tumor treatment in order to achieve complete ablation. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  9. Distribution of ventilation/perfusion ratios in pulmonary embolism: an adjunct to the interpretation of ventilation/perfusion lung scans.

    PubMed

    Itti, Emmanuel; Nguyen, Séverine; Robin, Fabrice; Desarnaud, Serge; Rosso, Jean; Harf, Alain; Meignan, Michel

    2002-12-01

    Diagnosis of pulmonary embolism (PE) by visual interpretation of ventilation/perfusion (V/Q) scans is limited by the high percentages of patients classified in the intermediate- and low-probability categories. This study proposes a quantitative analysis of the distribution of V/Q ratios to better identify patients with PE. We studied 99 consecutive patients who underwent dual-isotope (81m)Kr/(99m)Tc-macroaggregate V/Q scanning and arterial blood gas analysis within 48 h. The 8-view V/Q scans were visually analyzed by 2 observers according to the revised criteria of the Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) (normal scan or low, intermediate, or high probability of PE). Quantitative analysis of the posterior-view distribution histogram of V/Q ratios was performed using dedicated software. Briefly, regions of interest were drawn around the lungs on the matched V/Q images, smooth filtering was applied, normalized regional V/Q ratios were calculated within each pixel, and a distribution histogram was built. Patients with normal scans (n = 16) had a predominance of V/Q ratios (63.3% +/- 13.0%) between 0.8 and 1.2. They had only 9.8% +/- 5.8% of ratios > 1.2, and the remaining 26.9% +/- 7.5% of ratios were <0.8. By contrast, patients with PE (n = 34) were characterized by a significant increase (15.5 +/- 10.0%, P = 0.04) in high V/Q ratios (>1.2) and a significant increase (34.5% +/- 8.2%, P = 0.003) in low V/Q ratios (<0.8). Interestingly, a similar pattern was found in patients with a high PIOPED probability of PE, 21.3% +/- 11.0% and 37.5% +/- 9.2%, respectively. Within the nondiagnostic group (intermediate- + low-probability scans, n = 58), 17 patients were finally diagnosed with PE. Analysis of the distribution histogram in this group allowed the identification of 5 patients with PE (specificity, 78%). A quantitative approach to lung scan interpretation, based on the distribution histogram of V/Q ratios, may be helpful for categorizing

  10. Ex Vivo Perfusion With Adenosine A2A Receptor Agonist Enhances Rehabilitation of Murine Donor Lungs After Circulatory Death.

    PubMed

    Stone, Matthew L; Sharma, Ashish K; Mas, Valeria R; Gehrau, Ricardo C; Mulloy, Daniel P; Zhao, Yunge; Lau, Christine L; Kron, Irving L; Huerter, Mary E; Laubach, Victor E

    2015-12-01

    Ex vivo lung perfusion (EVLP) enables assessment and rehabilitation of marginal donor lungs before transplantation. We previously demonstrated that adenosine A2A receptor (A2AR) agonism attenuates lung ischemia-reperfusion injury. The current study utilizes a novel murine EVLP model to test the hypothesis that A2AR agonist enhances EVLP-mediated rehabilitation of donation after circulatory death (DCD) lungs. Mice underwent euthanasia and 60 minutes warm ischemia, and lungs were flushed with Perfadex and underwent cold static preservation (CSP, 60 minutes). Three groups were studied: no EVLP (CSP), EVLP with Steen solution for 60 minutes (EVLP), and EVLP with Steen solution supplemented with ATL1223, a selective A2AR agonist (EVLP + ATL1223). Lung function, wet/dry weight, cytokines and neutrophil numbers were measured. Microarrays were performed using the Affymetrix GeneChip Mouse Genome 430A 2.0 Array. Ex vivo lung perfusion significantly improved lung function versus CSP, which was further, significantly improved by EVLP + ATL1223. Lung edema, cytokines, and neutrophil counts were reduced after EVLP and further, significantly reduced after EVLP + ATL1223. Gene array analysis revealed differential expression of 1594 genes after EVLP, which comprise canonical pathways involved in inflammation and innate immunity including IL-1, IL-8, IL-6, and IL-17 signaling. Several pathways were uniquely regulated by EVLP + ATL1223 including the downregulation of genes involved in IL-1 signaling, such as ADCY9, ECSIT, IRAK1, MAPK12, and TOLLIP. Ex vivo lung perfusion modulates proinflammatory genes and reduces pulmonary dysfunction, edema, and inflammation in DCD lungs, which are further reduced by A2AR agonism. This murine EVLP model provides a novel platform to study rehabilitative mechanisms of DCD lungs.

  11. Betamethasone treatment and fetal lung perfusion evaluated with color Doppler energy imaging.

    PubMed

    Dubiel, M; Gudmundsson, S; Pirhonen, J; Breborowicz, G H; Marsal, K

    1997-10-01

    The aim of this study was semiquantitative evaluation of tissue blood flow in the fetal lung before and after administration of betamethasone. This was carried out by means of computer analysis of ultrasound Doppler signals obtained by the color Doppler energy (CDE) technique. CDE signals were recorded in 20 singleton pregnancies with appropriate growth and imminent preterm delivery between 26 and 33 weeks of gestation. The CDE signal recordings were made before and after intramuscular administration of betamethasone 8 mg/day for 3 days. Fixed preset CDE system control settings for the fetal right lung were used during the examinations. Images from CDE scans were recorded on S-VHS videotape and transmitted for computer analysis of 8-bit images at 256 gray-scale levels. The mean flow signal intensity was recorded for the fetal lung before and after betamethasone administration. Additionally, blood velocity waveforms were measured in the intrapulmonary arteries and veins in the peripheral part of the lung. CDE signals from the fetal lung indicated increased energy values after corticosteroid treatment in 16 cases. In three cases there was no change in CDE signal values, and in one case a fall of the signal value was noted. Blood velocity waveforms from the intrapulmonary arteries showed decreased resistance to flow in 15 cases, increased resistance to flow in four cases and no change in one case. No significant differences in venous blood flow velocities were found. In conclusion, the results suggest that there is an increase in fetal lung blood perfusion after maternal corticosteroid administration.

  12. Pharmacological Reconditioning of Marginal Donor Rat Lungs Using Inhibitors of Peroxynitrite and Poly (ADP-ribose) Polymerase During Ex Vivo Lung Perfusion.

    PubMed

    Wang, Xingyu; Wang, Yabo; Parapanov, Roumen; Abdelnour, Etienne; Gronchi, Fabrizio; Perentes, Jean Yannis; Piquilloud, Lise; Ris, Hans-Beat; Letovanec, Igor; Liaudet, Lucas; Krueger, Thorsten

    2016-07-01

    Donor lungs obtained after prolonged warm ischemia (WI) may be unsuitable for transplantation due to the risk of reperfusion injury, but could be reconditioned using ex-vivo lung perfusion (EVLP). Key processes of reperfusion injury include the formation of reactive oxygen species (ROS)/nitrogen species (RNS) and the activation of poly(adenosine diphosphate-ribose) polymerase (PARP). We explored whether rat lungs obtained after WI could be reconditioned during EVLP using the ROS/RNS scavenger Mn(III)-tetrakis (4-benzoic acid) porphyrin chloride (MnTBAP) or the PARP inhibitor 3-aminobenzamide (3-AB). Rat lungs obtained after 3 hours cold ischemia (CI group, control), or 1 hour WI plus 2 hours CI (WI group) were placed in an EVLP circuit for normothermic perfusion for 3 hours. Lungs retrieved after WI were treated or not with 3-AB (1 mg/mL) or MnTBAP (0.3 mg/mL), added to the perfusate. Measurements included physiological variables (lung compliance, vascular resistance, oxygenation capacity), lung weight gain, levels of proteins, lactate dehydrogenase, protein carbonyl (marker of ROS), 3-nitrotyrosine (marker of RNS), poly(adenosine diphosphate-ribose) (PAR, marker of PARP activation) and IL-6, in the bronchoalveolar lavage or the lung tissue, and histology. In comparison to the CI group, the lungs from the WI group displayed higher protein carbonyls, 3-nitrotyrosine, PAR, lactate dehydrogenase and proteins in bronchoalveolar lavage, lung weight gain, perivascular edema, as well as reduced static compliance, but similar oxygenation. All these alterations were markedly attenuated by 3-AB and MnTBAP. After EVLP, lungs obtained after WI exhibit oxidative stress, PARP activation, and tissue injury, which are suppressed by pharmacological inhibitors of ROS/RNS and PARP.

  13. Lung [(18)F]fluorodeoxyglucose uptake and ventilation-perfusion mismatch in the early stage of experimental acute smoke inhalation.

    PubMed

    Musch, Guido; Winkler, Tilo; Harris, R Scott; Vidal Melo, Marcos F; Wellman, Tyler J; de Prost, Nicolas; Kradin, Richard L; Venegas, Jose G

    2014-03-01

    Acute lung injury occurs in a third of patients with smoke inhalation injury. Its clinical manifestations usually do not appear until 48-72 h after inhalation. Identifying inflammatory changes that occur in pulmonary parenchyma earlier than that could provide insight into the pathogenesis of smoke-induced acute lung injury. Furthermore, noninvasive measurement of such changes might lead to earlier diagnosis and treatment. Because glucose is the main source of energy for pulmonary inflammatory cells, the authors hypothesized that its pulmonary metabolism is increased shortly after smoke inhalation, when classic manifestations of acute lung injury are not yet expected. In five sheep, the authors induced unilateral injury with 48 breaths of cotton smoke while the contralateral lung served as control. The authors used positron emission tomography with: (1) [F]fluorodeoxyglucose to measure metabolic activity of pulmonary inflammatory cells; and (2) [N]nitrogen in saline to measure shunt and ventilation-perfusion distributions separately in the smoke-exposed and control lungs. The pulmonary [F]fluorodeoxyglucose uptake rate was increased at 4 h after smoke inhalation (mean ± SD: 0.0031 ± 0.0013 vs. 0.0026 ± 0.0010 min; P < 0.05) mainly as a result of increased glucose phosphorylation. At this stage, there was no worsening in lung aeration or shunt. However, there was a shift of perfusion toward units with lower ventilation-to-perfusion ratio (mean ratio ± SD: 0.82 ± 0.10 vs. 1.12 ± 0.02; P < 0.05) and increased heterogeneity of the ventilation-perfusion distribution (mean ± SD: 0.21 ± 0.07 vs. 0.13 ± 0.01; P < 0 .05). Using noninvasive imaging, the authors demonstrated that increased pulmonary [F]fluorodeoxyglucose uptake and ventilation-perfusion mismatch occur early after smoke inhalation.

  14. The matching of ventilation and perfusion in the lung of the Tegu lizard, Tupinambis nigropunctatus.

    PubMed

    Hlastala, M P; Standaert, T A; Pierson, D J; Luchtel, D L

    1985-06-01

    Ventilation-perfusion (VA/Q) distribution was evaluated in the Tegu lizard, Tupinambis nigropunctatus, using the multiple inert gas elimination technique (MIGET) in order to define the limitations to gas exchange in the large chambered unicameral lung. The lizards (0.52-1.1 kg) were anesthetized with halothane and ventilated. Body temperature was maintained at 35 degrees C. Arterial and sinus venosus PO2 averaged 79.4 +/- 5.9 and 47.3 +/- 6.4 torr while breathing air and 232.1 +/- 31 and 64.8 +/- 11.5 torr while breathing oxygen. VA/Q distributions were broad and right-to-left shunt averaged 21% while breathing air and 27% while breathing oxygen. Gas exchange was significantly impaired due to the presence of both shunt and VA/Q heterogeneity. The walls of the lung enclose a large axial air chamber. Microscopic examination revealed approximately three generations of septa which subdivided the wall into tubular-shaped gas-exchange chambers. Wall thickness averages 2.8 mm at the anterior end of the lung, 2.1 mm in the middle portion of the lung and 1.4 mm at the posterior end. The thickness of the blood-air barrier (epithelial-basal lamina-endothelial cell layer) ranged from 0.35 to 0.90 micron. Although this barrier is slightly thicker than in the mammalian lung (0.1-0.5 micron), it is unlikely to be a source of diffusion limitation in gas exchange at rest.

  15. Pulmonary effects and disposition of luteolin and Artemisia afra extracts in isolated perfused lungs.

    PubMed

    Joel Mjiqiza, Sizwe; Abraham Syce, James; Chibuzo Obikeze, Kenechukwu

    2013-10-07

    Artemisia afra (Asteraceae) is a traditional medicinal plant frequently used in steam inhalation form to treat respiratory conditions. Quantify luteolin content in Artemisia afra dried crude and aqueous extract. Evaluate the pulmonary effects of Artemisia afra steam inhalation, nebulized Artemisia afra extract and luteolin in isolated perfused lungs (IPL). Evaluate the pulmonary disposition of intravenously administered luteolin. HPLC was used to quantify luteolin in Artemisia afra extracts. A modified version of the IPL was used to determine the effects of Artemisia afra steam inhalation, nebulized luteolin, and nebulized aqueous leaf extract on lung function, as well as the pulmonary disposition of IV luteolin. Artemisia afra extract contained significantly higher luteolin levels than the crude dried leaves. Inhaled Artemisia afra steam, and nebulized luteolin, and Artemisia afra extract and IV luteolin produced significant dose-dependent improvements in lung function, with nebulized Artemisia afra producing the greatest improvements. Nebulisation with Artemisia afra extract yielded higher quantities of luteolin than luteolin nebulisation. Results verify the traditional use of inhalation of Artemisia afra steam, although nebulized luteolin and aqueous extract are better alternatives. Luteolin significantly contributes to the bronchodilatory effects of Artemisia afra. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  16. Multislice Analysis of Blood Flow Values in CT Perfusion Studies of Lung Cancer

    PubMed Central

    Malavasi, Silvia; Barone, Domenico; Gavelli, Giampaolo

    2017-01-01

    Objectives. Tumour heterogeneity represents a key issue in CT perfusion (CTp), where all studies are usually based on global mean or median values of perfusion maps, often computed on whole tumour. We sought to determine whether, and to what extent, such global values can be representative of tumour heterogeneity, with respect to single slices, and could be used for therapy assessment. Materials and Methods. Twelve patients with one primary non-small cell lung cancer lesion were enrolled in this study, for a total amount of 26 CTp examinations and 118 slices. Mean and median blood flow (BF) values, calculated voxel-based, were computed on each slice and the whole tumour. To measure functional heterogeneity, entropy was calculated on BF values as well. Results. Most of the slices were not represented by the global BF values computed on the whole tumour. In addition, there are a number of lesions having equivalent global BF values, but they are composed of slices having very different heterogeneity distributions, that is, entropy values. Conclusions. Global mean/median BF values of the single slices separately should be considered for clinical assessment, only if interpreted through entropy computed on BF values. The numerical equivalence between global BF values of different lesions may correspond to different clinical status, thus inducing possible errors in choice of therapy when considering global values only. PMID:28164118

  17. Validation of measurements of ventilation-to-perfusion ratio inequality in the lung from expired gas

    NASA Technical Reports Server (NTRS)

    Prisk, G. Kim; Guy, Harold J B.; West, John B.; Reed, James W.

    2003-01-01

    The analysis of the gas in a single expirate has long been used to estimate the degree of ventilation-perfusion (Va/Q) inequality in the lung. To further validate this estimate, we examined three measures of Va/Q inhomogeneity calculated from a single full exhalation in nine anesthetized mongrel dogs under control conditions and after exposure to aerosolized methacholine. These measurements were then compared with arterial blood gases and with measurements of Va/Q inhomogeneity obtained using the multiple inert gas elimination technique. The slope of the instantaneous respiratory exchange ratio (R slope) vs. expired volume was poorly correlated with independent measures, probably because of the curvilinear nature of the relationship due to continuing gas exchange. When R was converted to the intrabreath Va/Q (iV/Q), the best index was the slope of iV/Q vs. volume over phase III (iV/Q slope). This was strongly correlated with independent measures, especially those relating to inhomogeneity of perfusion. The correlations for iV/Q slope and R slope considerably improved when only the first half of phase III was considered. We conclude that a useful noninvasive measurement of Va/Q inhomogeneity can be derived from the intrabreath respiratory exchange ratio.

  18. Validation of measurements of ventilation-to-perfusion ratio inequality in the lung from expired gas

    NASA Technical Reports Server (NTRS)

    Prisk, G. Kim; Guy, Harold J B.; West, John B.; Reed, James W.

    2003-01-01

    The analysis of the gas in a single expirate has long been used to estimate the degree of ventilation-perfusion (Va/Q) inequality in the lung. To further validate this estimate, we examined three measures of Va/Q inhomogeneity calculated from a single full exhalation in nine anesthetized mongrel dogs under control conditions and after exposure to aerosolized methacholine. These measurements were then compared with arterial blood gases and with measurements of Va/Q inhomogeneity obtained using the multiple inert gas elimination technique. The slope of the instantaneous respiratory exchange ratio (R slope) vs. expired volume was poorly correlated with independent measures, probably because of the curvilinear nature of the relationship due to continuing gas exchange. When R was converted to the intrabreath Va/Q (iV/Q), the best index was the slope of iV/Q vs. volume over phase III (iV/Q slope). This was strongly correlated with independent measures, especially those relating to inhomogeneity of perfusion. The correlations for iV/Q slope and R slope considerably improved when only the first half of phase III was considered. We conclude that a useful noninvasive measurement of Va/Q inhomogeneity can be derived from the intrabreath respiratory exchange ratio.

  19. Mechanical factors and the regulation of perfusion through atelectatic lung in pigs.

    PubMed

    Enjeti, S; Terry, P B; Menkes, H A; Traystman, R J

    1982-03-01

    The role of mechanical interdependence in the perfusion of atelectatic lung was studied in two ways: a) regional hemodynamics were compared before (control) and after the development of lobar and sublobar atelectasis, and b) the effect of thoracotomy on regional hemodynamics was assessed. With lobar atelectasis mean lobar blood flow and vascular conductance decreased to 60% of control. Sublobar atelectasis caused mean sublobar blood flow and vascular conductance to decrease to 6% of control. Opening the chest after production of lobar atelectasis caused blood flow to fall to 50% of control. When sublobar atelectasis was produced in the open chest, sublobar blood flow decreased to 25% of control measurements made prior to thoracotomy. We conclude that with a closed chest, sublobar vascular distortion mediated by mechanical interdependence may be an important mechanism responsible for the differences in hemodynamic responses to atelectasis between lobes and sublobar regions.

  20. Novel Flurometric Tool to Assess Mitochondrial Redox State of Isolated Perfused Rat Lungs After Exposure to Hyperoxia

    PubMed Central

    Audi, Said H.; Staniszewski, Kevin S.; Haworth, Steven T.; Jacobs, Elizabeth R.; Ranji, Mahsa; Zablocki, Clement J.

    2013-01-01

    Recently, we demonstrated the utility of optical fluorometry to detect a change in the redox status of mitochondrial autofluorescent coenzymes nicotinamide adenine dinucleotide (NADH) and oxidized form of flavin adenine dinucleotide \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{upgreek} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} }{}$({\\rm FADH}_{2})$\\end{document} (FAD), as a measure of mitochondrial function in isolated perfused rat lungs (IPL). The objective of this paper was to utilize optical fluorometry to evaluate the effect of rat exposure to hyperoxia (\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{upgreek} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} }{}${>}{95\\%}~{\\rm O}_{2}$\\end{document} for 48 h) on lung tissue mitochondrial redox status of NADH and FAD in a nondestructive manner in IPL. Surface NADH and FAD signals were measured before and after lung perfusion with perfusate containing rotenone (ROT, complex I inhibitor), potassium cyanide (KCN, complex IV inhibitor), and/or pentachlorophenol (PCP, uncoupler). ROT- or KCN-induced increase in NADH signal is considered a measure of complex I activity, and KCN-induced decrease in FAD signal is considered a measure of complex II activity. The results show that hyperoxia decreased complex I and II activities by 63% and 55%, respectively, when compared to lungs of rats exposed to room air (normoxic rats). Mitochondrial complex I and II activities in lung homogenates were also lower (77% and 63%, respectively) for hyperoxic than for normoxic lungs. These results suggest that the mitochondrial matrix is more reduced in hyperoxic lungs than in normoxic lungs, and demonstrate the ability of optical fluorometry to detect a change

  1. Pulmonary vascular volume ratio measured by cardiac computed tomography in children and young adults with congenital heart disease: comparison with lung perfusion scintigraphy.

    PubMed

    Goo, Hyun Woo; Park, Sang Hyub

    2017-06-23

    Lung perfusion scintigraphy is regarded as the gold standard for evaluating differential lung perfusion ratio in congenital heart disease. To compare cardiac CT with lung perfusion scintigraphy for estimated pulmonary vascular volume ratio in patients with congenital heart disease. We included 52 children and young adults (median age 4 years, range 2 months to 28 years; 31 males) with congenital heart disease who underwent cardiac CT and lung perfusion scintigraphy without an interim surgical or transcatheter intervention and within 1 year. We calculated the right and left pulmonary vascular volumes using threshold-based CT volumetry. Then we compared right pulmonary vascular volume percentages at cardiac CT with right lung perfusion percentages at lung perfusion scintigraphy by using paired t-test and Bland-Altman analysis. The right pulmonary vascular volume percentages at cardiac CT (66.3 ± 14.0%) were significantly smaller than the right lung perfusion percentages at lung perfusion scintigraphy (69.1 ± 15.0%; P=0.001). Bland-Altman analysis showed a mean difference of -2.8 ± 5.8% and 95% limits of agreement (-14.1%, 8.5%) between these two variables. Cardiac CT, in a single examination, can offer pulmonary vascular volume ratio in addition to pulmonary artery anatomy essential for evaluating peripheral pulmonary artery stenosis in patients with congenital heart disease. However there is a wide range of agreement between cardiac CT and lung perfusion scintigraphy.

  2. Review of criteria appropriate for a very low probability of pulmonary embolism on ventilation-perfusion lung scans: a position paper.

    PubMed

    Stein, P D; Gottschalk, A

    2000-01-01

    The "low-probability" interpretation of ventilation-perfusion lung scans has been characterized as misleading or even dangerous because of the high prevalence of pulmonary embolism associated with such an interpretation. Since the completion of the Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) study, analyses of the PIOPED database have allowed identification of several abnormalities seen on ventilation-perfusion scans that have a positive predictive value (PPV) for pulmonary embolism of less than 10%. These include nonsegmental perfusion abnormalities (PPV = 8%), perfusion defects smaller than the corresponding areas of increased opacity at chest radiography (PPV = 8%), matched ventilation-perfusion abnormalities in two or three zones of a single lung (PPV = 3%), one to three small segmental perfusion defects (PPV = 1%), triple matched defects in the upper or middle lung zone (PPV = 4%), and the stripe sign (PPV = 7%). Use of these abnormalities as interpretative criteria constitutes "very low probability" interpretation and will reduce the number of low-probability interpretations of ventilation-perfusion lung scans, which may be considered nondiagnostic because of the unacceptably high rate of false-negative results. This will enhance the utility of the ventilation-perfusion lung scan for screening patients with suspected pulmonary embolism.

  3. 99mTc technegas ventilation and perfusion lung scintigraphy for the diagnosis of pulmonary embolus.

    PubMed

    Howarth, D M; Lan, L; Thomas, P A; Allen, L W

    1999-04-01

    Lung scintigraphy is used widely for diagnosis of pulmonary embolus (PE). Technegas ventilation imaging has many advantages over other methods, but little outcome data exists on this technique. The aims of this study were to better define the role of lung scintigraphy in the management of patients with suspected PE and to evaluate technegas ventilation imaging by following patient outcomes. A group of 717 out of 834 consecutive patients, referred to a university teaching hospital for lung scintigraphy to confirm or refute the diagnosis of PE, was followed for 18-30 mo to determine clinical outcome. The follow-up endpoints were death as a result of PE, death as a result of hemorrhage after treatment for PE, uncomplicated survival, survival with subsequent PE, nonfatal hemorrhage after treatment for PE and recurrence of PE in treated patients. Ventilation imaging was performed using technegas, and perfusion imaging was performed using intravenous 99mTc macroaggregated albumin. The modified PIOPED (Prospective Investigation of Pulmonary Embolism Diagnosis) diagnostic criterion was used for interpretation of lung scintigraphy. Diagnostic results included 3.5% normal studies, 67.4% assessed as low probability for PE, 10% as moderate probability for PE and 19.1% as high probability for PE. A total of 231 patents received therapy with heparin, followed by warfarin, including those receiving anticoagulation therapy for other conditions. Ninety-six percent of patients with normal and low probability studies (n = 508) had good outcomes, 6 patients died as a result of PE and 12 subsequently developed PE. The odds ratio for death by PE in this group was 0.2. Of the 72 moderate probability studies, 39 patients were untreated. In this group there was 1 death due to PE, and PE subsequently developed in 2 patients. None of the remaining 33 treated patients died, but 4 patients experienced bleeding complications. The odds ratio for death by PE in the moderate probability group was

  4. The gravitational distribution of ventilation-perfusion ratio is more uniform in prone than supine posture in the normal human lung

    PubMed Central

    Sá, Rui Carlos; Theilmann, Rebecca J.; Buxton, Richard B.; Prisk, G. Kim; Hopkins, Susan R.

    2013-01-01

    The gravitational gradient of intrapleural pressure is suggested to be less in prone posture than supine. Thus the gravitational distribution of ventilation is expected to be more uniform prone, potentially affecting regional ventilation-perfusion (V̇a/Q̇) ratio. Using a novel functional lung magnetic resonance imaging technique to measure regional V̇a/Q̇ ratio, the gravitational gradients in proton density, ventilation, perfusion, and V̇a/Q̇ ratio were measured in prone and supine posture. Data were acquired in seven healthy subjects in a single sagittal slice of the right lung at functional residual capacity. Regional specific ventilation images quantified using specific ventilation imaging and proton density images obtained using a fast gradient-echo sequence were registered and smoothed to calculate regional alveolar ventilation. Perfusion was measured using arterial spin labeling. Ventilation (ml·min−1·ml−1) images were combined on a voxel-by-voxel basis with smoothed perfusion (ml·min−1·ml−1) images to obtain regional V̇a/Q̇ ratio. Data were averaged for voxels within 1-cm gravitational planes, starting from the most gravitationally dependent lung. The slope of the relationship between alveolar ventilation and vertical height was less prone than supine (−0.17 ± 0.10 ml·min−1·ml−1·cm−1 supine, −0.040 ± 0.03 prone ml·min−1·ml−1·cm−1, P = 0.02) as was the slope of the perfusion-height relationship (−0.14 ± 0.05 ml·min−1·ml−1·cm−1 supine, −0.08 ± 0.09 prone ml·min−1·ml−1·cm−1, P = 0.02). There was a significant gravitational gradient in V̇a/Q̇ ratio in both postures (P < 0.05) that was less in prone (0.09 ± 0.08 cm−1 supine, 0.04 ± 0.03 cm−1 prone, P = 0.04). The gravitational gradients in ventilation, perfusion, and regional V̇a/Q̇ ratio were greater supine than prone, suggesting an interplay between thoracic cavity configuration, airway and vascular tree anatomy, and the effects of

  5. The gravitational distribution of ventilation-perfusion ratio is more uniform in prone than supine posture in the normal human lung.

    PubMed

    Henderson, A Cortney; Sá, Rui Carlos; Theilmann, Rebecca J; Buxton, Richard B; Prisk, G Kim; Hopkins, Susan R

    2013-08-01

    The gravitational gradient of intrapleural pressure is suggested to be less in prone posture than supine. Thus the gravitational distribution of ventilation is expected to be more uniform prone, potentially affecting regional ventilation-perfusion (Va/Q) ratio. Using a novel functional lung magnetic resonance imaging technique to measure regional Va/Q ratio, the gravitational gradients in proton density, ventilation, perfusion, and Va/Q ratio were measured in prone and supine posture. Data were acquired in seven healthy subjects in a single sagittal slice of the right lung at functional residual capacity. Regional specific ventilation images quantified using specific ventilation imaging and proton density images obtained using a fast gradient-echo sequence were registered and smoothed to calculate regional alveolar ventilation. Perfusion was measured using arterial spin labeling. Ventilation (ml·min(-1)·ml(-1)) images were combined on a voxel-by-voxel basis with smoothed perfusion (ml·min(-1)·ml(-1)) images to obtain regional Va/Q ratio. Data were averaged for voxels within 1-cm gravitational planes, starting from the most gravitationally dependent lung. The slope of the relationship between alveolar ventilation and vertical height was less prone than supine (-0.17 ± 0.10 ml·min(-1)·ml(-1)·cm(-1) supine, -0.040 ± 0.03 prone ml·min(-1)·ml(-1)·cm(-1), P = 0.02) as was the slope of the perfusion-height relationship (-0.14 ± 0.05 ml·min(-1)·ml(-1)·cm(-1) supine, -0.08 ± 0.09 prone ml·min(-1)·ml(-1)·cm(-1), P = 0.02). There was a significant gravitational gradient in Va/Q ratio in both postures (P < 0.05) that was less in prone (0.09 ± 0.08 cm(-1) supine, 0.04 ± 0.03 cm(-1) prone, P = 0.04). The gravitational gradients in ventilation, perfusion, and regional Va/Q ratio were greater supine than prone, suggesting an interplay between thoracic cavity configuration, airway and vascular tree anatomy, and the effects of gravity on Va/Q matching.

  6. Lung [18F]fluorodeoxyglucose uptake and ventilation-perfusion mismatch in the early stage of experimental acute smoke inhalation

    PubMed Central

    Musch, Guido; Winkler, Tilo; Harris, R. Scott; Vidal Melo, Marcos F.; Wellman, Tyler J.; de Prost, Nicolas; Kradin, Richard L.; Venegas, Jose G.

    2014-01-01

    Background Acute lung injury (ALI) occurs in a third of patients with smoke inhalation injury. Its clinical manifestations usually do not appear until 48 to 72 h after inhalation. Identifying inflammatory changes that occur in pulmonary parenchyma earlier than that could provide insight into the pathogenesis of smoke-induced ALI. Furthermore, noninvasive measurement of such changes might lead to earlier diagnosis and treatment. Because glucose is the main source of energy for pulmonary inflammatory cells, we hypothesized that its pulmonary metabolism is increased shortly after smoke inhalation, when classic manifestations of ALI are not yet expected. Methods In five sheep we induced unilateral injury with 48 breaths of cotton smoke while the contralateral lung served as control. We used positron emission tomography with: 1) [18F]fluorodeoxyglucose to measure pulmonary inflammatory cell metabolic activity; and 2) [13N]nitrogen in saline to measure shunt and ventilation-perfusion distributions separately in the smoke-exposed and control lungs. Results The pulmonary [18F]fluorodeoxyglucose uptake rate was increased at 4 h after smoke inhalation (mean ± SD: 0.0031 ± 0.0013 vs. 0.0026 ± 0.0010 min−1, P < 0.05) mainly as a result of increased glucose phosphorylation. At this stage there was no worsening in lung aeration or shunt. However, there was a shift of perfusion toward units with lower ventilation-to-perfusion ratio (mean ratio ± SD: 0.82 ± 0.10 vs. 1.12 ± 0.02, P < 0.05) and increased heterogeneity of the ventilation-perfusion distribution (mean ± SD: 0.21 ± 0.07 vs. 0.13 ± 0.01, P < 0.05). Conclusion Using noninvasive imaging we demonstrated that increased pulmonary [18F]fluorodeoxyglucose uptake and ventilation-perfusion mismatch occur early after smoke inhalation. PMID:24051392

  7. (68)Ga PET Ventilation and Perfusion Lung Imaging-Current Status and Future Challenges.

    PubMed

    Bailey, Dale L; Eslick, Enid M; Schembri, Geoffrey P; Roach, Paul J

    2016-09-01

    Gallium-68 ((68)Ga) is a positron-emitting radionuclide suitable for positron emission tomography (PET) imaging that has a number of convenient features-it has a physical half life of 68 minutes, it is generator produced at the PET facility and needs no local cyclotron, and being a radiometal is able to be chelated to a number of useful molecules for diagnostic imaging with PET. (68)Ga has recently been investigated as a radiotracer for ventilation and perfusion (V/Q) lung imaging. It is relatively easy to produce both V/Q radiopharmaceuticals labeled with (68)Ga for PET studies, it offers higher spatial resolution than equivalent SPECT studies, the short half life allows for multiple (repeated) scans on the same day, and low amounts of radiotracer can be used thus limiting the radiation dose to the subject. In the usual clinical setting requiring a V/Q scan, that of suspected pulmonary embolism, the role of (68)Ga V/Q PET may be limited from a logistical perspective, however, in nonacute applications such as lung function evaluation, radiotherapy treatment planning, and respiratory physiology investigations it would appear to be an ideal modality to employ. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Multipotent adult progenitor cells decrease cold ischemic injury in ex vivo perfused human lungs: an initial pilot and feasibility study.

    PubMed

    La Francesca, Saverio; Ting, Anthony E; Sakamoto, Jason; Rhudy, Jessica; Bonenfant, Nicholas R; Borg, Zachary D; Cruz, Fernanda F; Goodwin, Meagan; Lehman, Nicholas A; Taggart, Jennifer M; Deans, Robert; Weiss, Daniel J

    2014-01-01

    Primary graft dysfunction (PGD) is a significant cause of early morbidity and mortality following lung transplantation. Improved organ preservation techniques will decrease ischemia-reperfusion injury (IRI) contributing to PGD. Adult bone marrow-derived adherent stem cells, including mesenchymal stromal (stem) cells (MSCs) and multipotent adult progenitor cells (MAPCs), have potent anti-inflammatory actions, and we thus postulated that intratracheal MAPC administration during donor lung processing would decrease IRI. The goal of the study was therefore to determine if intratracheal MAPC instillation would decrease lung injury and inflammation in an ex vivo human lung explant model of prolonged cold storage and subsequent reperfusion. Four donor lungs not utilized for transplant underwent 8 h of cold storage (4°C). Following rewarming for approximately 30 min, non-HLA-matched allogeneic MAPCs (1 × 10(7) MAPCs/lung) were bronchoscopically instilled into the left lower lobe (LLL) and vehicle comparably instilled into the right lower lobe (RLL). The lungs were then perfused and mechanically ventilated for 4 h and subsequently assessed for histologic injury and for inflammatory markers in bronchoalveolar lavage fluid (BALF) and lung tissue. All LLLs consistently demonstrated a significant decrease in histologic and BALF inflammation compared to vehicle-treated RLLs. These initial pilot studies suggest that use of non-HLA-matched allogeneic MAPCs during donor lung processing can decrease markers of cold ischemia-induced lung injury.

  9. Non-contrast-enhanced perfusion and ventilation assessment of the human lung by means of fourier decomposition in proton MRI.

    PubMed

    Bauman, Grzegorz; Puderbach, Michael; Deimling, Michael; Jellus, Vladimir; Chefd'hotel, Christophe; Dinkel, Julien; Hintze, Christian; Kauczor, Hans-Ulrich; Schad, Lothar R

    2009-09-01

    Assessment of regional lung perfusion and ventilation has significant clinical value for the diagnosis and follow-up of pulmonary diseases. In this work a new method of non-contrast-enhanced functional lung MRI (not dependent on intravenous or inhalative contrast agents) is proposed. A two-dimensional (2D) true fast imaging with steady precession (TrueFISP) pulse sequence (TR/TE = 1.9 ms/0.8 ms, acquisition time [TA] = 112 ms/image) was implemented on a 1.5T whole-body MR scanner. The imaging protocol comprised sets of 198 lung images acquired with an imaging rate of 3.33 images/s in coronal and sagittal view. No electrocardiogram (ECG) or respiratory triggering was used. A nonrigid image registration algorithm was applied to compensate for respiratory motion. Rapid data acquisition allowed observing intensity changes in corresponding lung areas with respect to the cardiac and respiratory frequencies. After a Fourier analysis along the time domain, two spectral lines corresponding to both frequencies were used to calculate the perfusion- and ventilation-weighted images. The described method was applied in preliminary studies on volunteers and patients showing clinical relevance to obtain non-contrast-enhanced perfusion and ventilation data.

  10. An experimental study of the recovery of injured porcine lungs with prolonged normothermic cellular ex vivo lung perfusion following donation after circulatory death.

    PubMed

    Spratt, John R; Mattison, Lars M; Iaizzo, Paul A; Brown, Roland Z; Helms, Haylie; Iles, Tinen L; Howard, Brian; Panoskaltsis-Mortari, Angela; Loor, Gabriel

    2017-09-01

    Donation after circulatory death (DCD) is an underused source of donor lungs. Normothermic cellular ex vivo lung perfusion (EVLP) is effective in preserving standard donor lungs but may also be useful in the preservation and assessment of DCD lungs. Using a model of DCD and prolonged EVLP, the effects of donor warm ischemia and postmortem ventilation on graft recovery were evaluated. Adult male swine underwent general anesthesia and heparinization. In the control group (n = 4), cardioplegic arrest was induced and the lungs were procured immediately. In the four treatment groups, a period of agonal hypoxia was followed by either 1 h of warm ischemia with (n = 4) or without (n = 4) ventilation or 2 h of warm ischemia with (n = 4) or without (n = 4) ventilation. All lungs were studied on an EVLP platform for 24 h. Hemodynamic measures, compliance, and oxygenation on EVLP were worse in all DCD lungs compared with controls. Hemodynamics and compliance normalized in all lungs after 24 h of EVLP, but DCD lungs demonstrated impaired oxygenation. Normothermic cellular EVLP is effective in preserving and monitoring of DCD lungs. Early donor postmortem ventilation and timely procurement lead to improved graft function. © 2017 Steunstichting ESOT.

  11. Phase II multicenter clinical trial of pulmonary metastasectomy and isolated lung perfusion with melphalan in patients with resectable lung metastases.

    PubMed

    den Hengst, Willem A; Hendriks, Jeroen M H; Balduyck, Bram; Rodrigus, Inez; Vermorken, Jan B; Lardon, Filip; Versteegh, Michel I M; Braun, Jerry; Gelderblom, Hans; Schramel, Franz M N H; Van Boven, Wim-Jan; Van Putte, Bart P; Birim, Özcan; Maat, Alexander P W M; Van Schil, Paul E Y

    2014-10-01

    The 5-year overall survival rate of patients undergoing complete surgical resection of pulmonary metastases (PM) from colorectal cancer (CRC) and sarcoma remains low (20-50%). Local recurrence rate is high (48-66%). Isolated lung perfusion (ILuP) allows the delivery of high-dose locoregional chemotherapy with minimal systemic leakage to improve local control. From 2006 to 2011, 50 patients, 28 male, median age 57 years (15-76), with PM from CRC (n = 30) or sarcoma (n = 20) were included in a phase II clinical trial conducted in four cardiothoracic surgical centers. In total, 62 ILuP procedures were performed, 12 bilaterally, with 45 mg of melphalan at 37°C, followed by resection of all palpable PM. Survival was calculated according to the Kaplan-Meier method. Operative mortality was 0%, and 90-day morbidity was mainly respiratory (grade 3: 42%, grade 4: 2%). After a median follow-up of 24 months (3-63 mo), 18 patients died, two without recurrence. Thirty patients had recurrent disease. Median time to local pulmonary progression was not reached. The 3-year overall survival and disease-free survival were 57% ± 9% and 36% ± 8%, respectively. Lung function data showed a decrease in forced expiratory volume in 1 second and diffusing capacity of the alveolocapillary membrane of 21.6% and 25.8% after 1 month, and 10.4% and 11.3% after 12 months, compared with preoperative values. Compared with historical series of PM resection without ILuP, favorable results are obtained in terms of local control without long-term adverse effects. These data support the further investigation of ILuP as additional treatment in patients with resectable PM from CRC or sarcoma.

  12. Quantitative ventilation-perfusion lung scans in infants and children: utility of a submicronic radiolabeled aerosol to assess ventilation

    SciTech Connect

    O'Brodovich, H.M.; Coates, G.

    1984-09-01

    The quantitative assessment of regional pulmonary ventilation and perfusion provides useful information regarding lung function. Its use in infants and young children, however, has been minimal because of practical and technical limitations when the distribution of ventilation is assessed by radioactive gases. In 16 infants and children we used an inexpensive commercially available nebulizer to produce a submicronic aerosol labeled with 99mtechnetium-diethylenetriamine pentacetic acid to assess ventilation quantitatively, and intravenous injections of 99mtechnetium-labeled macroaggregates of albumin to assess pulmonary perfusion quantitatively. Studies were safely completed in both ambulatory and critically ill patients, including two premature infants who had endotracheal tubes in place for ventilatory support. No sedation or patient cooperation is required. This technique enables any department of nuclear medicine to measure regional pulmonary ventilation and perfusion in infants and children.

  13. Lung scans with significant perfusion defects limited to matching pleural effusions have a low probability of pulmonary embolism

    SciTech Connect

    Datz, F.L.; Bedont, R.A.; Taylor, A.

    1985-05-01

    Patients with a pleural effusion on chest x-ray often undergo a lung scan to exclude pulmonary embolism (PE). According to other studies, when the scan shows a perfusion defect equal in size to a radiographic abnormality on chest x-ray, the scan should be classified as indeterminate or intermediate probability for PE. However, since those studies dealt primarily with alveolar infiltrates rather than pleural effusions, the authors undertook a retrospective study to determine the probability of PE in patients with pleural effusion and a matching perfusion defect. The authors reviewed 451 scans and x-rays of patients studied for suspected PE. Of those, 53 had moderate or large perfusion defects secondary to pleural effusion without other significant (>25% of a segment) effusion without other significant (>25% of a segment) defects on the scan. Final diagnosis was confirmed by pulmonary angiography (16), thoracentesis (40), venography (11), other radiographic and laboratory studies, and clinical course. Of the 53 patients, only 2 patients had venous thrombotic disease. One patient had PE on pulmonary angiography, the other patient had thrombophlebitis on venography. The remainder of the patients had effusions due to congestive heart failure (12), malignancy (12), infection (7), trauma (7), collegen vascular disease (7), sympathetic effusion (3) and unknown etiology (3). The authors conclude that lung scans with significant perfusion defects limited to matching pleural effusions on chest x-ray have a low probability for PE.

  14. Pulmonary embolism among patients with a nearly normal ventilation/perfusion lung scan.

    PubMed

    Henry, J W; Stein, P D; Gottschalk, A; Raskob, G E

    1996-08-01

    Among patients with nearly normal ventilation/perfusion (V/Q) lung scans in the Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED), pulmonary embolism (PE) was diagnosed more frequently in those who underwent pulmonary angiography than in those in whom PE was diagnosed on the basis of an adverse outcome while receiving no anticoagulant therapy. This may suggest that an adverse outcome is not apparent in patients with PE of such mild severity that the V/Q scan is nearly normal. If this were the case, patients with mild PE might not require treatment. The purpose of this investigation was to evaluate patients in PIOPED with nearly normal-V/Q lung scans. The V/Q scans and clinical characteristics of those in whom PE was diagnosed or excluded by pulmonary angiography (angiography group) were compared with those in whom PE was diagnosed or excluded by the presence or absence of an adverse outcome while not receiving anticoagulant therapy (outcome group). If the characteristics were the same, it would suggest that some patients with mild PE do well without treatment. If the characteristics were different, it would indicate that there is no evidence from these data that mild PE need not be treated. Data from PIOPED were evaluated from patients with suspected acute PE who had V/Q scans interpreted as nearly normal. There were 75 patients in the angiography group and 90 patients in the outcome group. Patients with entirely normal V/Q scans were excluded. PE was more frequent in the angiography group than in the outcome group, 8 of 75 (11%) vs 0 of 90 (0%) (p < 0.01). In patients with nearly normal V/Q scans who were in the outcome group in comparison to the angiography group, the V/Q scan showed fewer mismatched segmental perfusion defects, a lower percentage of low-probability V/Q interpretations by one of the two V/Q readers (compared with very low or normal probability), and a generally lower clinical assessment. The observed lower frequency of PE in the

  15. Standardized perfusion value: universal CT contrast enhancement scale that correlates with FDG PET in lung nodules.

    PubMed

    Miles, K A; Griffiths, M R; Fuentes, M A

    2001-08-01

    The standardized enhancement value and standardized perfusion value allow comparison between different methods for quantification of contrast enhancement during computed tomography (CT). Standard perfusion values calculated from CT measurements of perfusion within pulmonary nodules compared favorably with those derived from previously reported enhancement data and correlated with standardized uptake values obtained from positron emission tomographic images (r = 0.8, P <.01).

  16. Pyrrolidine dithiocarbamate administered during ex-vivo lung perfusion promotes rehabilitation of injured donor rat lungs obtained after prolonged warm ischemia

    PubMed Central

    Francioli, Cyril; Wang, Xingyu; Parapanov, Roumen; Abdelnour, Etienne; Lugrin, Jérôme; Gronchi, Fabrizio; Perentes, Jean; Eckert, Philippe; Ris, Hans-Beat; Piquilloud, Lise

    2017-01-01

    Damaged lung grafts obtained after circulatory death (DCD lungs) and warm ischemia may be at high risk of reperfusion injury after transplantation. Such lungs could be pharmacologically reconditioned using ex-vivo lung perfusion (EVLP). Since acute inflammation related to the activation of nuclear factor kappaB (NF-κB) is instrumental in lung reperfusion injury, we hypothesized that DCD lungs might be treated during EVLP by pyrrolidine dithiocarbamate (PDTC), an inhibitor of NF-κB. Rat lungs exposed to 1h warm ischemia and 2 h cold ischemia were subjected to EVLP during 4h, in absence (CTRL group, N = 6) or in presence of PDTC (2.5g/L, PDTC group, N = 6). Static pulmonary compliance (SPC), peak airway pressure (PAWP), pulmonary vascular resistance (PVR), and oxygenation capacity were determined during EVLP. After EVLP, we measured the weight gain of the heart-lung block (edema), and the concentration of LDH (cell damage), proteins (permeability edema) and of the cytokines IL-6, TNF-α and CINC-1 in bronchoalveolar lavage (BAL), and we evaluated NF-κB activation by the degree of phosphorylation and degradation of its inhibitor IκBα in lung tissue. In CTRL, we found significant NF-κB activation, lung edema, and a massive release of LDH, proteins and cytokines. SPC significantly decreased, PAWP and PVR increased, while oxygenation tended to decrease. Treatment with PDTC during EVLP inhibited NF-κB activation, did not influence LDH release, but markedly reduced lung edema and protein concentration in BAL, suppressed TNFα and IL-6 release, and abrogated the changes in SPC, PAWP and PVR, with unchanged oxygenation. In conclusion, suppression of innate immune activation during EVLP using the NF-κB inhibitor PDTC promotes significant improvement of damaged rat DCD lungs. Future studies will determine if such rehabilitated lungs are suitable for in vivo transplantation. PMID:28323904

  17. Pyrrolidine dithiocarbamate administered during ex-vivo lung perfusion promotes rehabilitation of injured donor rat lungs obtained after prolonged warm ischemia.

    PubMed

    Francioli, Cyril; Wang, Xingyu; Parapanov, Roumen; Abdelnour, Etienne; Lugrin, Jérôme; Gronchi, Fabrizio; Perentes, Jean; Eckert, Philippe; Ris, Hans-Beat; Piquilloud, Lise; Krueger, Thorsten; Liaudet, Lucas

    2017-01-01

    Damaged lung grafts obtained after circulatory death (DCD lungs) and warm ischemia may be at high risk of reperfusion injury after transplantation. Such lungs could be pharmacologically reconditioned using ex-vivo lung perfusion (EVLP). Since acute inflammation related to the activation of nuclear factor kappaB (NF-κB) is instrumental in lung reperfusion injury, we hypothesized that DCD lungs might be treated during EVLP by pyrrolidine dithiocarbamate (PDTC), an inhibitor of NF-κB. Rat lungs exposed to 1h warm ischemia and 2 h cold ischemia were subjected to EVLP during 4h, in absence (CTRL group, N = 6) or in presence of PDTC (2.5g/L, PDTC group, N = 6). Static pulmonary compliance (SPC), peak airway pressure (PAWP), pulmonary vascular resistance (PVR), and oxygenation capacity were determined during EVLP. After EVLP, we measured the weight gain of the heart-lung block (edema), and the concentration of LDH (cell damage), proteins (permeability edema) and of the cytokines IL-6, TNF-α and CINC-1 in bronchoalveolar lavage (BAL), and we evaluated NF-κB activation by the degree of phosphorylation and degradation of its inhibitor IκBα in lung tissue. In CTRL, we found significant NF-κB activation, lung edema, and a massive release of LDH, proteins and cytokines. SPC significantly decreased, PAWP and PVR increased, while oxygenation tended to decrease. Treatment with PDTC during EVLP inhibited NF-κB activation, did not influence LDH release, but markedly reduced lung edema and protein concentration in BAL, suppressed TNFα and IL-6 release, and abrogated the changes in SPC, PAWP and PVR, with unchanged oxygenation. In conclusion, suppression of innate immune activation during EVLP using the NF-κB inhibitor PDTC promotes significant improvement of damaged rat DCD lungs. Future studies will determine if such rehabilitated lungs are suitable for in vivo transplantation.

  18. Lung cancer nanomedicine: potentials and pitfalls.

    PubMed

    Bölükbas, Deniz Ali; Meiners, Silke

    2015-01-01

    Lung cancer is by far the most common cause of cancer-related deaths in the world. Nanoparticle-based therapies enable targeted drug delivery for lung cancer treatment with increased therapeutic efficiency and reduced systemic toxicity. At the same time, nanomedicine has the potential for multimodal treatment of lung cancer that may involve 'all-in-one' targeting of several tumor-associated cell types in a timely and spatially controlled manner. Therapeutic approaches, however, are hampered by a translational gap between basic scientists, clinicians and pharma industry due to suboptimal animal models and difficulties in scale-up production of nanoagents. This calls for a disease-centered approach with interdisciplinary basic and clinical research teams with the support of pharma industries.

  19. Focally perfused succinate potentiates brain metabolism in head injury patients.

    PubMed

    Jalloh, Ibrahim; Helmy, Adel; Howe, Duncan J; Shannon, Richard J; Grice, Peter; Mason, Andrew; Gallagher, Clare N; Stovell, Matthew G; van der Heide, Susan; Murphy, Michael P; Pickard, John D; Menon, David K; Carpenter, T Adrian; Hutchinson, Peter J; Carpenter, Keri Lh

    2016-01-01

    Following traumatic brain injury, complex cerebral energy perturbations occur. Correlating with unfavourable outcome, high brain extracellular lactate/pyruvate ratio suggests hypoxic metabolism and/or mitochondrial dysfunction. We investigated whether focal administration of succinate, a tricarboxylic acid cycle intermediate interacting directly with the mitochondrial electron transport chain, could improve cerebral metabolism. Microdialysis perfused disodium 2,3-(13)C2 succinate (12 mmol/L) for 24 h into nine sedated traumatic brain injury patients' brains, with simultaneous microdialysate collection for ISCUS analysis of energy metabolism biomarkers (nine patients) and nuclear magnetic resonance of (13)C-labelled metabolites (six patients). Metabolites 2,3-(13)C2 malate and 2,3-(13)C2 glutamine indicated tricarboxylic acid cycle metabolism, and 2,3-(13)C2 lactate suggested tricarboxylic acid cycle spinout of pyruvate (by malic enzyme or phosphoenolpyruvate carboxykinase and pyruvate kinase), then lactate dehydrogenase-mediated conversion to lactate. Versus baseline, succinate perfusion significantly decreased lactate/pyruvate ratio (p = 0.015), mean difference -12%, due to increased pyruvate concentration (+17%); lactate changed little (-3%); concentrations decreased for glutamate (-43%) (p = 0.018) and glucose (-15%) (p = 0.038). Lower lactate/pyruvate ratio suggests better redox status: cytosolic NADH recycled to NAD(+) by mitochondrial shuttles (malate-aspartate and/or glycerol 3-phosphate), diminishing lactate dehydrogenase-mediated pyruvate-to-lactate conversion, and lowering glutamate. Glucose decrease suggests improved utilisation. Direct tricarboxylic acid cycle supplementation with 2,3-(13)C2 succinate improved human traumatic brain injury brain chemistry, indicated by biomarkers and (13)C-labelling patterns in metabolites.

  20. Pulmonary vasomotor nerve responses in isolated perfused lungs of Macaca mulatta and Papio species.

    PubMed Central

    de Burgh Daly, I; Ramsay, D J; Waaler, B A

    1975-01-01

    1. Lung lobes of Macaca mulatta and Papio species were isolated from the body and perfused by a pump delivering a constant volume inflow. The left atrial pressure was kept constant and therefore any recorded change in pulmonary arterial pressure reflected a change in pulmonary vascular resistance. 2. In five Macaca mulatta preparations stimulation of the upper thoracic sympathetic chain, the stellate ganglion, the middle cervical ganglion and the thoracic vagosympathetic nerve caused a small increase in calculated pulmonary vascular resistance usually followed by a larger decrease. Evidence is produced which suggests that the depressor response is mediated by adrenergic beta-receptors. In three preparations no change in pulmonary vascular resistance occurred. 3. In four Papio preparations stimulation of similar nerves invariably caused an increase in calculated pulmonary vascular resistance. In one animal no change in vascular resistance occurred. 4. A regression analysis of the results showed an inverse relationship between the magnitude of the pulmonary vascular response to nerve stimulation and the degree of excitement of the animals during capture, restraint and anaesthesia (P less than 0.01). Images Fig. 2 PMID:809575

  1. Automatic extraction of PIOPED interpretations from ventilation/perfusion lung scan reports.

    PubMed

    Fiszman, M; Haug, P J; Frederick, P R

    1998-01-01

    Free-text documents are the main type of data produced by a radiology department in a hospital information system. While this type of data is readily accessible for clinical data review it can not be accessed by other applications to perform medical decision support, quality assurance, and outcome studies. In an attempt to solve this problem, natural language processing systems have been developed and tested against chest x-rays reports to extract relevant clinical information and make it accessible to other computer applications. We have used a natural language processing tool called SymText to extract relevant clinical information from a different type of radiology report, the Ventilation/Perfusion lung scan report. Results of this effort can be analyzed in terms of precision and recall. The overall precision was 0.88 and recall was 0.92. In addition, the natural language processing system functions differently in reports with and without an impression section. If this type of information can be successfully extracted from radiology reports, one can develop quality monitors for the diagnostic performance of the radiologist by correlating the impressions with gold standard data present in a hospital information system. Avoiding the manual effort previously necessary to create quality assurance data, can lead to a higher frequency of quality review in a radiology department.

  2. Automatic extraction of PIOPED interpretations from ventilation/perfusion lung scan reports.

    PubMed Central

    Fiszman, M.; Haug, P. J.; Frederick, P. R.

    1998-01-01

    Free-text documents are the main type of data produced by a radiology department in a hospital information system. While this type of data is readily accessible for clinical data review it can not be accessed by other applications to perform medical decision support, quality assurance, and outcome studies. In an attempt to solve this problem, natural language processing systems have been developed and tested against chest x-rays reports to extract relevant clinical information and make it accessible to other computer applications. We have used a natural language processing tool called SymText to extract relevant clinical information from a different type of radiology report, the Ventilation/Perfusion lung scan report. Results of this effort can be analyzed in terms of precision and recall. The overall precision was 0.88 and recall was 0.92. In addition, the natural language processing system functions differently in reports with and without an impression section. If this type of information can be successfully extracted from radiology reports, one can develop quality monitors for the diagnostic performance of the radiologist by correlating the impressions with gold standard data present in a hospital information system. Avoiding the manual effort previously necessary to create quality assurance data, can lead to a higher frequency of quality review in a radiology department. PMID:9929341

  3. Platelet Vascular Endothelial Growth Factor is a Potential Mediator of Transfusion-Related Acute Lung Injury

    PubMed Central

    Maloney, James P; Ambruso, Daniel R; Voelkel, Norbert F; Silliman, Christopher C

    2015-01-01

    Objective The occurrence of non-hemolytic transfusion reactions is highest with platelet and plasma administration. Some of these reactions are characterized by endothelial leak, especially transfusion related acute lung injury (TRALI). Elevated concentrations of inflammatory mediators secreted by contaminating leukocytes during blood product storage may contribute to such reactions, but platelet-secreted mediators may also contribute. We hypothesized that platelet storage leads to accumulation of the endothelial permeability mediator vascular endothelial growth factor (VEGF), and that intravascular administration of exogenous VEGF leads to extensive binding to its lung receptors. Methods Single donor, leukocyte-reduced apheresis platelet units were sampled over 5 days of storage. VEGF protein content of the centrifuged supernatant was determined by ELISA, and the potential contribution of VEGF from contaminating leukocytes was quantified. Isolated-perfused rat lungs were used to study the uptake of radiolabeled VEGF administered intravascularly, and the effect of unlabeled VEGF on lung leak. Results There was a time-dependent release of VEGF into the plasma fraction of the platelet concentrates (62 ± 9 pg/ml on day one, 149 ± 23 pg/ml on day 5; mean ± SEM, p<0.01, n=8) and a contribution by contaminating leukocytes was excluded. Exogenous 125I-VEGF bound avidly and specifically to the lung vasculature, and unlabeled VEGF in the lung perfusate caused vascular leak. Conclusion Rising concentrations of VEGF occur during storage of single donor platelet concentrates due to platelet secretion or disintegration, but not due to leukocyte contamination. Exogenous VEGF at these concentrations rapidly binds to its receptors in the lung vessels. At higher VEGF concentrations, VEGF causes vascular leak in uninjured lungs. These data provide further evidence that VEGF may contribute to the increased lung permeability seen in TRALI associated with platelet products. PMID

  4. Whole-tumor perfusion CT in patients with advanced lung adenocarcinoma treated with conventional and antiangiogenetic chemotherapy: initial experience.

    PubMed

    Fraioli, Francesco; Anzidei, Michele; Zaccagna, Fulvio; Mennini, Maria Luisa; Serra, Goffredo; Gori, Bruno; Longo, Flavia; Catalano, Carlo; Passariello, Roberto

    2011-05-01

    To determine whether wide-volume perfusion computed tomography (CT) performed with a new generation scanner can allow evaluation of the effects of chemotherapy combined with antiangiogenetic treatment on the whole tumor mass in patients with locally advanced lung adenocarcinoma and to determine if changes in CT numbers correlate with the response to therapy as assessed by conventional response evaluation criteria in solid tumors (RECIST). Forty-five patients with unresectable lung adenocarcinoma underwent perfusion CT before and 40 and 90 days after chemotherapy and antiangiogenetic treatment. RECIST measurements and calculations of blood flow, blood volume, time to peak, and permeability were performed by two independent blinded radiologists. Pearson correlation coefficient was used to assess the correlation between baseline CT numbers. Baseline and follow-up perfusion parameters of the neoplastic lesions were tested overall for statistically significant differences by using the repeated-measures analysis of variance and then were also compared on the basis of the therapy response assessed according to the RECIST criteria. Pearson correlation coefficient showed a significant correlation between baseline values of blood flow and blood volume (ρ = 0.48; P = .001), time to peak and permeability (ρ = 0.31; P = .04), time to peak and blood flow (ρ = -0.66; P < .001), and time to peak and blood volume (ρ = -0.39; P = .007). Blood flow, blood volume, and permeability values were higher in responding patients than in the other patients, with a significant difference at second follow-up for blood flow (P = .0001), blood volume (P = .02), and permeability (P = .0001); time to peak was higher in nonresponding patients (P = .012). Perfusion CT imaging may allow evaluation of lung cancer angiogenesis demonstrating alterations in vascularity following treatment. RSNA, 2011

  5. EGFR kinase domain mutation positive lung cancers are sensitive to intrapleural perfusion with hyperthermic chemotherapy (IPHC) complete treatment.

    PubMed

    Zhang, Hongjuan; Zhan, Cheng; Ke, Ji; Xue, Zhiqiang; Zhang, Aiqun; Xu, Kaifeng; Shen, Zhirong; Yu, Lei; Chen, Liang

    2016-01-19

    Lung cancer is the global leading cause of cancer-related deaths. A significant portion of lung cancer patients harbor kinase domain mutations in the epidermal growth factor receptor (EGFR). While EGFR tyrosine kinase inhibitors (TKI) effectively shrink tumors harboring mutant EGFR, clinical efficacy is limited by the development of TKI resistance. Effective alternatives are desperately needed in clinic for treating EGFR kinase domain mutation positive lung cancer. In our clinic in treating M1a lung cancer patients through intrapleural perfusion with hyperthermic chemotherapy (IPHC) followed by cycles of systemic chemotherapy (we termed this procedure IPHC complete treatment, IPHC-CT), we found dramatic tumor shrinkage in mutant EGFR-positive patients. We further confirmed the sensitivity of EGFR mutation-positive lung cancer cell lines derived from patients to HC (hyperthermic chemotherapy) treatment. We found that hyperthermia promoted accumulation of cisplatin in lung cancer cells. Hyperthermia and cisplatin synergistically downregulated the EGFR protein level, leading to quenching of signal from EGFR and induction of apoptosis. Our work therefore showed IPHC-CT is an effective treatment for EGFR kinase domain mutation positive lung cancer patients.

  6. Changes in distribution of lung perfusion and ventilation at rest and during maximal exercise

    SciTech Connect

    Mohsenifar, Z.; Ross, M.D.; Waxman, A.; Goldbach, P.; Koerner, S.K.

    1985-03-01

    A new method for evaluation of changes in the distribution of pulmonary perfusion and ventilation during exercise was applied to normal male volunteers. Ventilation and perfusion scans were done with the subjects seated on a bicycle ergometer. The resting studies utilized krypton 81 (/sup 81m/Kr) for ventilation and technetium /sup 99m/ (/sup 99m/Tc) macroaggregate albumin intravenously for perfusion. Exercise studies were done when 80 percent of maximum predicted heart rate was maintained for five minutes and utilized /sup 81m/Kr for ventilation and a tenfold dose of /sup 99m/Tc for perfusion. Higher dose of /sup 99m/Tc would minimize the effect of radioactivity left over from the resting study. This method allowed us to assess changes in ventilation and perfusion in normal subjects induced by exercise, but may also be applicable in a variety of cardiopulmonary conditions that affect pulmonary ventilation and perfusion or both.

  7. Is it possible to further improve the function of pulmonary grafts by extending the duration of lung reconditioning using ex vivo lung perfusion?

    PubMed

    Pierre, L; Lindstedt, S; Hlebowicz, J; Ingemansson, R

    2013-07-01

    The method of ex vivo lung perfusion (EVLP) has been suggested as a reliable means of differentiating between "good" and "poor" pulmonary grafts in marginal donors as, when grafts identified as good by this method are transplanted, the results do not differ from those using lungs fulfilling standard criteria. The EVLP method is also thought to improve pulmonary grafts by reducing lung edema and eliminating lung atelectasis. In the present study, we investigated whether the pulmonary graft could be further improved by extending the duration of EVLP. Six Landrace pigs were used. The lungs were reconditioned and evaluated, using the EVLP method, as double lungs. After the initial evaluation, EVLP was continued for a further 90 minutes. The arterial oxygen level (pO2) was 60.8 ± 4.8 kPa after the standard 60 minutes of EVLP and 67.1 ± 2.2 kPa after 150 minutes (p = 0.48). The pulmonary vascular resistance was 453 ± 78 dyne*s/cm(5) after 60, 90, 120 and 150 minutes of EVLP (p = 1.0). The pulmonary artery pressure was 17.8 ± 1.0 mmHg after 60, 90, 120, and 150 minutes of EVLP (p = 1.0) and the pulmonary artery flow was 3.5 ± 0.4 l/min after 60, 90, 120, and 150 minutes of EVLP (p = 1.0). The mean weight of the pulmonary grafts after harvesting was 574 ± 20 g at the beginning of EVLP 541 ± 24 g and, after 150 min of EVLP, 668 ± 33 (p = 0.011). The blood gases and hemodynamic parameters in the pulmonary grafts did not improve as a result of the extra 90 minutes of EVLP. However, the weight of the pulmonary graft increased significantly with increasing duration of EVLP, indicating lung perfusion injury.

  8. Ex vivo Perfusion with Adenosine A2A Receptor Agonist Enhances Rehabilitation of Murine Donor Lungs after Circulatory Death

    PubMed Central

    Stone, Mathew L.; Sharma, Ashish K.; Mas, Valeria. R.; Gehrau, Ricardo C.; Mulloy, Daniel P.; Zhao, Yunge; Lau, Christine L.; Kron, Irving L.; Laubach, Victor E.

    2015-01-01

    Background Ex vivo lung perfusion (EVLP) enables assessment and rehabilitation of marginal donor lungs prior to transplantation. We previously demonstrated that adenosine A2A receptor (A2AR) agonism attenuates lung ischemia-reperfusion injury. The current study utilizes a novel murine EVLP model to test the hypothesis that A2AR agonist enhances EVLP-mediated rehabilitation of donation after circulatory death (DCD) lungs. Methods Mice underwent euthanasia and 60 min warm ischemia, and lungs were flushed with Perfadex and underwent cold static preservation (CSP, 60 min). Three groups were studied: no EVLP (CSP), EVLP with Steen solution for 60 min (EVLP), and EVLP with Steen solution supplemented with ATL1223, a selective A2AR agonist (EVLP+ATL1223). Lung function, wet/dry weight, cytokines and neutrophil numbers were measured. Microarrays were performed using the Affymetrix GeneChip Mouse Genome 430A 2.0 Array. Results EVLP significantly improved lung function versus CSP, which was further, significantly improved by EVLP+ATL1223. Lung edema, cytokines and neutrophil counts were reduced after EVLP and further, significantly reduced after EVLP+ATL1223. Gene array analysis revealed differential expression of 1,594 genes after EVLP, which comprise canonical pathways involved in inflammation and innate immunity including IL-1, IL-8, IL-6 and IL-17 signaling. Several pathways were uniquely regulated by EVLP+ATL1223 including the downregulation of genes involved in IL-1 signaling such as ADCY9, ECSIT, IRAK1, MAPK12 and TOLLIP. Conclusion EVLP modulates pro-inflammatory genes and reduces pulmonary dysfunction, edema and inflammation in DCD lungs, which are further reduced by A2AR agonism. This murine EVLP model provides a novel platform to study rehabilitative mechanisms of DCD lungs. PMID:26262504

  9. Dynamic contrast-enhanced MRI perfusion for differentiating between melanoma and lung cancer brain metastases.

    PubMed

    Hatzoglou, Vaios; Tisnado, Jamie; Mehta, Alpesh; Peck, Kyung K; Daras, Mariza; Omuro, Antonio M; Beal, Kathryn; Holodny, Andrei I

    2017-04-01

    Brain metastases originating from different primary sites overlap in appearance and are difficult to differentiate with conventional MRI. Dynamic contrast-enhanced (DCE)-MRI can assess tumor microvasculature and has demonstrated utility in characterizing primary brain tumors. Our aim was to evaluate the performance of plasma volume (Vp) and volume transfer coefficient (K(trans) ) derived from DCE-MRI in distinguishing between melanoma and nonsmall cell lung cancer (NSCLC) brain metastases. Forty-seven NSCLC and 23 melanoma brain metastases were retrospectively assessed with DCE-MRI. Regions of interest were manually drawn around the metastases to calculate Vpmean and Kmeantrans. The Mann-Whitney U test and receiver operating characteristic analysis (ROC) were performed to compare perfusion parameters between the two groups. The Vpmean of melanoma brain metastases (4.35, standard deviation [SD] = 1.31) was significantly higher (P = 0.03) than Vpmean of NSCLC brain metastases (2.27, SD = 0.96). The Kmeantrans values were higher in melanoma brain metastases, but the difference between the two groups was not significant (P = 0.12). Based on ROC analysis, a cut-off value of 3.02 for Vpmean (area under curve = 0.659 with SD = 0.074) distinguished between melanoma brain metastases and NSCLC brain metastases (P < 0.01) with 72% specificity. Our data show the DCE-MRI parameter Vpmean can differentiate between melanoma and NSCLC brain metastases. The ability to noninvasively predict tumor histology of brain metastases in patients with multiple malignancies can have important clinical implications.

  10. [Effect of using several levels of positive end-expiratory pressure over barotrauma's induced lung injury in a model of isolated and perfused rabbit lungs].

    PubMed

    Trejo, Humberto; Urich, Daniela; Pezzulo, Alejandro; Novoa, Eva; Marcano, Héctor; Crespo, Astrid; Sánchez de León, Roberto

    2006-03-01

    The use of Positive end-expiratory pressure (PEEP) as a strategy of mechanical ventilation offers its advantages, such as improved oxygenation, without causing alveolar overstretching and barotrauma. We aim to investigate the effect of several levels of PEEP on barotrauma and, whether an optimal level of PEEP exists. Forty-eight New Zealand rabbits (2.5-3.5 kg) were divided into four groups with PEEP settings of 0, 4, 8 and 12 cmH2O, at increasing levels of inspiratory volume (IV). This was done in blood perfused rabbit lungs and in lungs perfused with a Buffer-Albumin Solution. We observed that lungs ventilated with PEEP 0 cmH2O suffered pulmonary rupture at high IV (300cc), with significant increases of Pap (Pulmonary artery pressure) and FFR (Fluid filtration rate). Lungs ventilated with PEEP 8 and 12 suffered pulmonary rupture at lower IV (200cc and 150cc vs. 300cc respectively) On the other hand, lungs ventilated with PEEP 4 cmH2O reached the highest IV (400cc), in addition, they showed the lowest elevations of Pap and FFR. The acellular lungs ventilated with PEEP 4, 8 and 12 showed pulmonary rupture at lower IV when compared with cellular ones (300cc vs. 400cc: 100cc vs. 200cc and 100cc vs. 150cc respectively). We concluded that an optimal PEEP exists, which protects against barotrauma, however, excess of PEEP could enhance its development. The blood could contain some mediators which attenuate the damage induced by barotrauma.

  11. Lung injury after simulated cardiopulmonary bypass in an isolated perfused rat lung preparation: Role of mitogen-activated protein kinase/Akt signaling and the effects of theophylline

    PubMed Central

    Markou, Thomais; Chambers, David J.

    2014-01-01

    Objectives Lung deflation and inflation during cardiac surgery with cardiopulmonary bypass contributes to pulmonary dysfunction postoperatively. Theophylline treatment for lung diseases has traditionally been thought to act by phosphodiesterase inhibition; however, increasing evidence has suggested other plausible mechanisms. We investigated the effects of deflation and reinflation on signaling pathways (p38-mitogen-activated protein kinase [MAPK], extracellular signal-regulated kinase 1 and 2 [ERK1/2], and Akt) and whether theophylline influences the deflation-induced lung injury and associated signaling. Methods Isolated rat lungs were perfused (15 mL/min) with deoxygenated rat blood in bicarbonate buffer and ventilated. After 20 minutes' equilibration, the lungs were deflated (60 minutes, aerobic perfusion 1.5 mL/min), followed by reinflation (60 minutes, anaerobic reperfusion 15 mL/min). Compliance, vascular resistance, and kinase phosphorylation were assessed during deflation and reinflation. The effects of SB203580 (50 μM), a p38-MAPK inhibitor, and theophylline (0.083 mM [therapeutic] or 3 mM [supratherapeutic]) on physiology and signaling were studied. Results Deflation reduced compliance by 44% compared with continuously ventilated lungs. p38-MAPK and Akt phosphorylation increased (three to fivefold) during deflation and reinflation, and ERK1/2 phosphorylation increased (approximately twofold) during reinflation. SB203580 had no effect on lung physiology or ERK1/2 and Akt activation. Both theophylline doses increased cyclic adenosine monophosphate, but only 3 mM theophylline improved compliance. p38-MAPK phosphorylation was not affected by theophylline; 0.083 mM theophylline inhibited reinflation-induced ERK1/2 phosphorylation (72% ± 3%); and 3 mM theophylline inhibited Akt phosphorylation during deflation (75% ± 5%) and reinflation (87% ± 4%). Conclusions Lung deflation and reinflation stimulates differential p38-MAPK, ERK1/2, and Akt activation

  12. Lung injury after simulated cardiopulmonary bypass in an isolated perfused rat lung preparation: Role of mitogen-activated protein kinase/Akt signaling and the effects of theophylline.

    PubMed

    Markou, Thomais; Chambers, David J

    2014-11-01

    Lung deflation and inflation during cardiac surgery with cardiopulmonary bypass contributes to pulmonary dysfunction postoperatively. Theophylline treatment for lung diseases has traditionally been thought to act by phosphodiesterase inhibition; however, increasing evidence has suggested other plausible mechanisms. We investigated the effects of deflation and reinflation on signaling pathways (p38-mitogen-activated protein kinase [MAPK], extracellular signal-regulated kinase 1 and 2 [ERK1/2], and Akt) and whether theophylline influences the deflation-induced lung injury and associated signaling. Isolated rat lungs were perfused (15 mL/min) with deoxygenated rat blood in bicarbonate buffer and ventilated. After 20 minutes' equilibration, the lungs were deflated (60 minutes, aerobic perfusion 1.5 mL/min), followed by reinflation (60 minutes, anaerobic reperfusion 15 mL/min). Compliance, vascular resistance, and kinase phosphorylation were assessed during deflation and reinflation. The effects of SB203580 (50 μM), a p38-MAPK inhibitor, and theophylline (0.083 mM [therapeutic] or 3 mM [supratherapeutic]) on physiology and signaling were studied. Deflation reduced compliance by 44% compared with continuously ventilated lungs. p38-MAPK and Akt phosphorylation increased (three to fivefold) during deflation and reinflation, and ERK1/2 phosphorylation increased (approximately twofold) during reinflation. SB203580 had no effect on lung physiology or ERK1/2 and Akt activation. Both theophylline doses increased cyclic adenosine monophosphate, but only 3 mM theophylline improved compliance. p38-MAPK phosphorylation was not affected by theophylline; 0.083 mM theophylline inhibited reinflation-induced ERK1/2 phosphorylation (72%±3%); and 3 mM theophylline inhibited Akt phosphorylation during deflation (75%±5%) and reinflation (87%±4%). Lung deflation and reinflation stimulates differential p38-MAPK, ERK1/2, and Akt activation, suggesting a role in lung injury during

  13. The Therapeutic Potential of Differentiated Lung Cells from Embryonic Stem Cells in Lung Diseases.

    PubMed

    Mokhber Dezfouli, Mohammad Reza; Chaleshtori, Sirous Sadeghian; Dehghan, Mohammad Mehdi; Tavanaeimanesh, Hamid; Baharvand, Hossein; Tahamtani, Yaser

    2017-01-01

    Lung diseases cause great morbidity and mortality. The choice of effective medical treatment is limited and the number of lung diseases are difficult to treat with current treatments. The embryonic stem cells (ESCs) have the potential to differentiate into cell types of all three germinal layers, including lung epithelial cells. So they can be a potential source for new cell therapies for hereditary or acquired diseases of the airways and lungs. One method for treatment of lung diseases is cell therapy and the use of ESCs that can replace the damaged epithelial and endothelial cells. Progress using ESCs has developed slowly for lung regeneration because differentiation of lung cells from ESCs is more difficult as compared to differentiation of other cells. The review studies the therapeutic effects of differentiated lung cells from embryonic stem cells in lung diseases. There are few studies of differentiation of ESCs into a lineage of respiratory and then investigation of this cell in experimental model of lung diseases.

  14. Lungs donated after circulatory death and prolonged warm ischemia are transplanted successfully after enhanced ex vivo lung perfusion using adenosine A2B receptor antagonism.

    PubMed

    Charles, Eric J; Mehaffey, J Hunter; Sharma, Ashish K; Zhao, Yunge; Stoler, Mark H; Isbell, James M; Lau, Christine L; Tribble, Curtis G; Laubach, Victor E; Kron, Irving L

    2017-04-12

    The current supply of acceptable donor lungs is not sufficient for the number of patients awaiting transplantation. We hypothesized that ex vivo lung perfusion (EVLP) with targeted drug therapy would allow successful rehabilitation and transplantation of donation after circulatory death lungs exposed to 2 hours of warm ischemia. Donor porcine lungs were procured after 2 hours of warm ischemia postcardiac arrest and subjected to 4 hours of cold preservation or EVLP. ATL802, an adenosine A2B receptor antagonist, was administered to select groups. Four groups (n = 4/group) were randomized: cold preservation (Cold), cold preservation with ATL802 during reperfusion (Cold + ATL802), EVLP (EVLP), and EVLP with ATL802 during ex vivo perfusion (EVLP + ATL802). Lungs subsequently were transplanted, reperfused, and assessed by measuring dynamic lung compliance and oxygenation capacity. EVLP + ATL802 significantly improved dynamic lung compliance compared with EVLP (25.0 ± 1.8 vs 17.0 ± 2.4 mL/cmH2O, P = .04), and compared with cold preservation (Cold: 12.2 ± 1.3, P = .004; Cold + ATL802: 10.6 ± 2.0 mL/cmH2O, P = .002). Oxygenation capacity was highest in EVLP (440.4 ± 37.0 vs Cold: 174.0 ± 61.3 mm Hg, P = .037). No differences in oxygenation or pulmonary edema were observed between EVLP and EVLP + ATL802. A significant decrease in interleukin-12 expression in tissue and bronchoalveolar lavage was identified between groups EVLP and EVLP + ATL802, along with less neutrophil infiltration. Severely injured donation after circulatory death lungs subjected to 2 hours of warm ischemia are transplanted successfully after enhanced EVLP with targeted drug therapy. Increased use of lungs after uncontrolled donor cardiac death and prolonged warm ischemia may be possible and may improve transplant wait list times and mortality. Copyright © 2017 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

  15. Reversal of diffuse patchy pattern in lung perfusion scan in a case of severe pulmonary arterial hypertension.

    PubMed

    Kodama, Yoshihiko; Abe, Kohtaro; Hosokawa, Kazuya; Ohtani, Kisho; Nagao, Michinobu; Hirooka, Yoshitaka; Sunagawa, Kenji

    2015-01-01

    A diffuse patchy pattern in the perfusion scan of the lung is a hallmark of severe pulmonary arterial hypertension (PAH). However, the mechanisms of this unique pattern remain uncertain. We here present the case of a 19-year-old woman with severe PAH who demonstrated reversal of the diffuse patchy pattern with improvement of pulmonary blood flow within a month after upfront triple combination therapy. Our case is a first report showing reversibility of diffuse patchy pattern by a short-term treatment in severe PAH. These findings suggest the possibility that the mechanisms underlying the diffuse patchy pattern may involve reversible vasoconstriction in addition to remodeling of small pulmonary arteries.

  16. In situ lung perfusion is a valuable tool to assess lungs from donation after circulatory death donors category I-II.

    PubMed

    Van De Wauwer, Caroline; Munneke, Anita J; Engels, Gerwin E; Berga, Foke M; Rakhorst, Gerhard; Nijsten, Maarten W; Mariani, Massimo A; Erasmus, Michiel E

    2013-05-01

    Donations after circulatory death (DCD) lung grafts are an alternative to extend the donor pool in lung transplantation. This study investigates the use of an in situ lung perfusion system (ISLP) in the donor to evaluate category I-II lungs. Pigs were sacrificed by ventricular fibrillation. All animals underwent 20 min of cardiopulmonary resuscitation and 5 min hands-off period after which heparin was administered. In group [WI-1], this was followed by 1 h of warm ischemia (WI) and 2 h of topical cooling (TC). In group [WI-2], 2 h of WI was followed by 1 h of TC. In group [WI-0], there was a minimal period of WI and no TC. In all three groups, the lungs were then evaluated during 60 min with ISLP. [WI-0] lungs showed a significantly higher compliance and Δ PO2 /FiO2 compared with [WI-1] and [WI-2]. PaCO2 and lactate production were higher in [WI-2] versus [WI-0]. Wet/Dry weight ratio was significantly higher in [WI-2] compared with [WI-0] in two lung biopsy locations. A high W/D weight ratio was correlated with a lower compliance, higher lactate production, and a higher PaCO2 . ISLP is an effective way to assess the quality of lungs from category I-II DCD donors. © 2013 The Authors Transplant International © 2013 European Society for Organ Transplantation. Published by Blackwell Publishing Ltd.

  17. Utility of ventilation and perfusion scan in the diagnosis of young military recruits with an incidental finding of hyperlucent lung.

    PubMed

    Arslan, N; Ilgan, S; Ozkan, M; Yuksekol, I; Bulakbasi, N; Pabuscu, Y; Ozguven; Bayhan, H

    2001-05-01

    Swyer-James-MacLeod syndrome (SJMS) is considered to be a relatively uncommon disease presenting with unilateral hyperlucent lung due to hypoplasia of a pulmonary artery and bronchiectasis of the affected lung. In this report, we describe the ventilation-perfusion (V/Q) scan findings of nine male recruits (aged 20-29 years, mean 24.4+/-2.96 years) with SJMS in whom the diagnosis was first established in adulthood. V/Q scan findings of all patients were compared with those on planar radiographs, pulmonary function studies, high resolution computed tomography (HRCT) and digital subtraction angiography (DSA). The ventilation (133Xe) and perfusion (99Tcm-macro-aggregated albumin) scans showed the characteristic pattern of a matched V/Q defect and marked air trapping on the washout phase on 133Xe scintigraphy. HRCT displayed hypodense lung with integrity of main airways, and markedly diminished vasculature on the affected side in all patients. A smaller pulmonary artery on the affected side with poor peripheral vasculature was observed with DSA in all patients. All patients had features of obstructive airway disease in varying degrees on pulmonary function studies. In contrast to other imaging methods, bronchiectasis as an etiological factor was displayed on HRCT. Some pulmonary areas, which were normal on HRCT and planar radiographs, showed air trapping on V/Q scan. Although a V/Q scan was more helpful in determining the extent of the disease and correlates well with conventional imaging methods, HRCT was the most valuable imaging method for the evaluation of aetiology in unilateral hyperlucent lung.

  18. Perfusion visualization and analysis for pulmonary embolism

    NASA Astrophysics Data System (ADS)

    Vaz, Michael S.; Kiraly, Atilla P.; Naidich, David P.; Novak, Carol L.

    2005-04-01

    Given the nature of pulmonary embolism (PE), timely and accurate diagnosis is critical. Contrast enhanced high-resolution CT images allow physicians to accurately identify segmental and sub-segmental emboli. However, it is also important to assess the effect of such emboli on the blood flow in the lungs. Expanding upon previous research, we propose a method for 3D visualization of lung perfusion. The proposed method allows users to examine perfusion throughout the entire lung volume at a single glance, with areas of diminished perfusion highlighted so that they are visible independent of the viewing location. This may be particularly valuable for better accuracy in assessing the extent of hemodynamic alterations resulting from pulmonary emboli. The method also facilitates user interaction and may help identify small peripheral sub-segmental emboli otherwise overlooked. 19 patients referred for possible PE were evaluated by CT following the administration of IV contrast media. An experienced thoracic radiologist assessed the 19 datasets with 17 diagnosed as being positive for PE with multiple emboli. Since anomalies in lung perfusion due to PE can alter the distribution of parenchymal densities, we analyzed features collected from histograms of the computed perfusion maps and demonstrate their potential usefulness as a preliminary test to suggest the presence of PE. These histogram features also offer the possibility of distinguishing distinct patterns associated with chronic PE and may even be useful for further characterization of changes in perfusion or overall density resulting from associated conditions such as pneumonia or diffuse lung disease.

  19. Regenerative potential of human airway stem cells in lung epithelial engineering.

    PubMed

    Gilpin, Sarah E; Charest, Jonathan M; Ren, Xi; Tapias, Luis F; Wu, Tong; Evangelista-Leite, Daniele; Mathisen, Douglas J; Ott, Harald C

    2016-11-01

    Bio-engineered organs for transplantation may ultimately provide a personalized solution for end-stage organ failure, without the risk of rejection. Building upon the process of whole organ perfusion decellularization, we aimed to develop novel, translational methods for the recellularization and regeneration of transplantable lung constructs. We first isolated a proliferative KRT5(+)TP63(+) basal epithelial stem cell population from human lung tissue and demonstrated expansion capacity in conventional 2D culture. We then repopulated acellular rat scaffolds in ex vivo whole organ culture and observed continued cell proliferation, in combination with primary pulmonary endothelial cells. To show clinical scalability, and to test the regenerative capacity of the basal cell population in a human context, we then recellularized and cultured isolated human lung scaffolds under biomimetic conditions. Analysis of the regenerated tissue constructs confirmed cell viability and sustained metabolic activity over 7 days of culture. Tissue analysis revealed extensive recellularization with organized tissue architecture and morphology, and preserved basal epithelial cell phenotype. The recellularized lung constructs displayed dynamic compliance and rudimentary gas exchange capacity. Our results underline the regenerative potential of patient-derived human airway stem cells in lung tissue engineering. We anticipate these advances to have clinically relevant implications for whole lung bioengineering and ex vivo organ repair.

  20. Diagnosis of pulmonary embolus using ventilation/perfusion lung scintigraphy: more than 0.5 segment of ventilation/perfusion mismatch is sufficient.

    PubMed

    Howarth, D M; Booker, J A; Voutnis, D D

    2006-05-01

    To determine the optimal diagnostic cut-off point using a simplified criterion for the detection of pulmonary embolus (PE) and to evaluate the criterion's utility and reporter reproducibility. Lung scintigraphy was carried out in 924 patients for the diagnosis of PE. This group consisted of 316 men and 608 women with median age of 63 years (range 18-94 years). Ventilation imaging was carried out with Tc-99m Technegas followed by perfusion imaging using 190 MBq Tc-99m macroaggregated albumin. Studies were classified using a 6-category probability criterion of incremental ventilation/perfusion (V/Q) mismatch: A, normal; B, low (minor matched V/Q defects or segmental matched V/Q defects without opacity on chest X-ray); C, low-moderate (a partial segment of V/Q mismatch); D, moderate (1 segment of mismatch); E, moderate-high (1-2 segments of V/Q mismatch) and F, high probability (=2 segments of V/Q mismatch). Clinical end-points at 3 and 6 months were death by PE or PE treated with anticoagulation therapy. Three-reporter reproducibility was determined by kappa statistic on a subgroup of patients (53/924). A total of 122 patients (13%) had a confirmed diagnosis of PE at 3 months and no additional cases were registered at 6 months. The lung scintigraphy probability classification showed: normal 152 (16%), low 620 (67%), low-moderate 20 (2%), moderate 28 (3%), moderate-high 24 (3%) and high 80 (9%). The respective sensitivities and specificities, where the diagnostic cut-offs were established at F, high; E, moderate-high; D, moderate and C, low-moderate probability, were F, 64 and 100%; E, 82 and 99%; D, 95 and 98% and C, 98 and 96%. The respective false-negative cases for F, E, D and C cut-offs were 44, 22, 7 and 3. Using the revised Prospective Investigation of Pulmonary Embolism Diagnosis reporting classification reporter agreement showed kappa values of 0.31-0.48. Using a simplified 2-category (>0.5 segment of V/Q mismatch positive, all others negative) criterion

  1. Relative preservation of peripheral lung function in smoking-related pulmonary emphysema: assessment with 99mTc-MAA perfusion and dynamic 133Xe SPET.

    PubMed

    Suga, K; Kume, N; Matsunaga, N; Ogasawara, N; Motoyama, K; Hara, A; Matsumoto, T

    2000-07-01

    In this study the cross-sectional functional differences between the central and peripheral lung in smokers with pulmonary emphysema were evaluated by lung perfusion and dynamic xenon-133 single-photon emission tomography (SPET). The subjects were 81 patients with a long-term smoking history and relatively advanced emphysema, 17 non-smoker patients with non-obstructive lung diseases and six healthy non-smokers. Regional lung functional difference between the peripheral and central lung was assessed in the upper, middle and lower lung zones by technetium-99m macroaggregated albumin SPET and dynamic 133Xe SPET. The distribution of emphysematous changes was assessed by density-mask computed tomography (CT) images which depicted abnormally low attenuation areas (LAAs) of less than -960 Hounsfield units. Two hundred and eighty-eight (59.2%) lung zones of 63 (77.7%) patients with pulmonary emphysema showed relative preservation of lung function in the peripheral lung, with a curvilinear band of normal perfusion (a stripe sign) and a significantly faster 133Xe half-clearance time (T(1/2)) than in central lung (P<0.0001). Of these lung zones, 256 (88.8%) showed central-dominant LAA distributions on density-mask CT images, but the remaining 32 zones did not show any regional preference in LAA distribution. Conversely, 117 (24.0%) lung zones of 19 (23.4%) patients showed periphery-dominant perfusion defects and LAA distributions, with significantly prolonged T(1/2) in the peripheral lung area (P<0.0001). The remaining 81 lung zones of the patients with pulmonary emphysema and all the lung zones of the healthy subjects and patients with non-obstructive lung diseases did not show a stripe sign, and no differences were observed in T(1/2) values and LAA distributions between the central and peripheral lung. Relative preservation of peripheral lung function seems to be a characteristic feature in smoking-related pulmonary emphysema, and may indicate a lower susceptibility of

  2. The effect of pumpless extracorporeal CO2 removal on regional perfusion of the brain in experimental acute lung injury.

    PubMed

    Kreyer, Stefan; Muders, Thomas; Luepschen, Henning; Kricklies, Corinna; Linden, Katharina; Soehle, Martin; Zinserling, Joerg; Putensen, Christian; Wrigge, Hermann

    2013-07-01

    Lung-protective mechanical ventilation with low tidal volumes (V(T)) is often associated with hypercapnia (HC), which may be unacceptable in patients with brain injury. CO2 removal using a percutaneous extracorporeal lung assist (pECLA) enables normocapnia despite low V(T), but its effects on regional cerebral blood flow (rCBF) remain ambiguous. We hypothesized that reversal of HC by pECLA impairs rCBF in a porcine lung injury model. Lung injury was induced in 9 anesthetized pigs by hydrochloric acid aspiration. rCBF and systemic hemodynamics were measured by colored microsphere technique and transpulmonary-thermodilution during a randomized sequence of 4 experimental situations: pECLA shunt-on (1) with HC and (2) without HC, pECLA shunt-off (3) with HC and (4) without HC. HC increased rCBF (P<0.05). CO2 removal with pECLA resulting in normocapnia, decreased rCBF to levels comparable to those without pECLA and normocapnia. HC resulted in increased cardiac output (+25.5%). Cardiac output was highest during HC with pECLA shunt (+44.9%). During pECLA with CO2 removal, cardiac output (+38.1%) decreased compared with pECLA without CO2 removal, but stayed higher than during normocapnia/no pECLA shunt (P<0.05). In this animal model, mechanical ventilation with low V(T) was associated with HC and increased rCBF. CO2 removal by pECLA restored normocapnia, reduced rCBF to levels of normocapnia, but required a higher systemic blood flow for the perfusion of the pECLA device. If these results could be transferred to patients, extracorporeal CO2 removal might be an option for treatment of combined lung and brain injury in condition of a sufficient cardiac flow reserve.

  3. Lung ventilation- and perfusion-weighted Fourier decomposition magnetic resonance imaging: in vivo validation with hyperpolarized 3He and dynamic contrast-enhanced MRI.

    PubMed

    Bauman, Grzegorz; Scholz, Alexander; Rivoire, Julien; Terekhov, Maxim; Friedrich, Janet; de Oliveira, Andre; Semmler, Wolfhard; Schreiber, Laura Maria; Puderbach, Michael

    2013-01-01

    The purpose of this work was to validate ventilation-weighted (VW) and perfusion-weighted (QW) Fourier decomposition (FD) magnetic resonance imaging (MRI) with hyperpolarized (3)He MRI and dynamic contrast-enhanced perfusion (DCE) MRI in a controlled animal experiment. Three healthy pigs were studied on 1.5-T MR scanner. For FD MRI, the VW and QW images were obtained by postprocessing of time-resolved lung image sets. DCE acquisitions were performed immediately after contrast agent injection. (3)He MRI data were acquired following the administration of hyperpolarized helium and nitrogen mixture. After baseline MR scans, pulmonary embolism was artificially produced. FD MRI and DCE MRI perfusion measurements were repeated. Subsequently, atelectasis and air trapping were induced, which followed with FD MRI and (3)He MRI ventilation measurements. Distributions of signal intensities in healthy and pathologic lung tissue were compared by statistical analysis. Images acquired using FD, (3)He, and DCE MRI in all animals before the interventional procedure showed homogeneous ventilation and perfusion. Functional defects were detected by all MRI techniques at identical anatomical locations. Signal intensity in VW and QW images was significantly lower in pathological than in healthy lung parenchyma. The study has shown usefulness of FD MRI as an alternative, noninvasive, and easily implementable technique for the assessment of acute changes in lung function. Copyright © 2012 Wiley Periodicals, Inc.

  4. Ventilation/perfusion SPECT or SPECT/CT for lung function imaging in patients with pulmonary emphysema?

    PubMed

    Froeling, Vera; Heimann, Uwe; Huebner, Ralf-Harto; Kroencke, Thomas J; Maurer, Martin H; Doellinger, Felix; Geisel, Dominik; Hamm, Bernd; Brenner, Winfried; Schreiter, Nils F

    2015-07-01

    To evaluate the utility of attenuation correction (AC) of V/P SPECT images for patients with pulmonary emphysema. Twenty-one patients (mean age 67.6 years) with pulmonary emphysema who underwent V/P SPECT/CT were included. AC/non-AC V/P SPECT images were compared visually and semiquantitatively. Visual comparison of AC/non-AC images was based on a 5-point likert scale. Semiquantitative comparison assessed absolute counts per lung (aCpLu) and lung lobe (aCpLo) for AC/non-AC images using software-based analysis; percentage counts (PC = (aCpLo/aCpLu) × 100) were calculated. Correlation between AC/non-AC V/P SPECT images was analyzed using Spearman's rho correlation coefficient; differences were tested for significance with the Wilcoxon rank sum test. Visual analysis revealed high conformity for AC and non-AC V/P SPECT images. Semiquantitative analysis of PC in AC/non-AC images had an excellent correlation and showed no significant differences in perfusion (ρ = 0.986) or ventilation (ρ = 0.979, p = 0.809) SPECT/CT images. AC of V/P SPECT images for lung lobe-based function imaging in patients with pulmonary emphysema do not improve visual or semiquantitative image analysis.

  5. More accurate quantification of pulmonary blood flow by magnetic resonance imaging than by lung perfusion scintigraphy in patients with fontan circulation.

    PubMed

    Fratz, Sohrab; Hess, John; Schwaiger, Markus; Martinoff, Stefan; Stern, Heiko C

    2002-09-17

    Quantitative evaluation of pulmonary perfusion using lung perfusion scintigraphy in patients with atriopulmonary anastomosis (APA) or total cavopulmonary connection (TCPC) or partial cavopulmonary connection (PCPC) is difficult because of preferential draining of the venae cavae to one lung. Scintigraphy is the gold standard. Phase-velocity MRI (PV-MRI) is a new technique for determining pulmonary perfusion. The aim of this study was therefore to determine whether PV-MRI is more accurate than scintigraphy for quantitative evaluation of pulmonary perfusion ratios in patients with APA, TCPC, or PCPC. We studied 15 patients with APA, TCPC, or PCPC (16+/-7 years old, 4 female). Twelve patients (15+/-8 years old, 3 female) with a single pulmonary blood source supplied by a subpulmonary ventricle, ensuring complete mixing of the radioactive tracer before entering the pulmonary circulation, served as controls. Pulmonary scintigraphy and PV-MRI were performed in all patients. Bland-Altman analysis showed a clinically unacceptable difference of 7.1% right pulmonary blood flow (27.2% upper and -13.0% lower limit of agreement) between the two methods in the study group. The two methods agreed excellently in the control group (difference, 1.6%; 4.0% upper and -7.2% lower limit of agreement), showing that the bad agreement in the study group was caused by the problems encountered using pulmonary scintigraphy in patients with APA, TCPC, or PCPC. Because of preferential caval flow into either lung, PV-MRI is more accurate for evaluating pulmonary perfusion ratios than lung perfusion scintigraphy in patients with Fontan-like circulation.

  6. Investigation of the potential causes of partial scan artifacts in dynamic CT myocardial perfusion imaging

    NASA Astrophysics Data System (ADS)

    Tao, Yinghua; Speidel, Michael; Szczykutowicz, Timothy; Chen, Guang-Hong

    2014-03-01

    In recent years, there have been several findings regarding CT number variations (partial scan artifact or PSA) across time in dynamic myocardial perfusion studies with short scan gated reconstruction. These variations are correlated with the view angle range corresponding to the short scan acquisition for a given cardiac phase, which can vary from one cardiac cycle to another due to the asynchrony between heart rate and gantry rotation speed. In this study, we investigate several potential causes of PSA, including noise, beam hardening and scatter, using numerical simulations. In addition, we investigate partial scan artifact in a single source 64-slice diagnostic CT scanner in vivo data sets, and report its effect on perfusion analysis. Results indicated that among all three factors investigated, scatter can cause obvious partial scan artifact in dynamic myocardial perfusion imaging. Further, scatter is a low frequency phenomenon and is not heavily dependent on the changing contrasts, as both the frequency method and the virtual scan method are effective in reducing partial scan artifact. However, PSA does not necessarily lead to different blood volume maps compared to the full scan, because these maps are usually generated with a curve fitting procedure.

  7. Accuracy and Utility of Deformable Image Registration in {sup 68}Ga 4D PET/CT Assessment of Pulmonary Perfusion Changes During and After Lung Radiation Therapy

    SciTech Connect

    Hardcastle, Nicholas; Hofman, Michael S.; Hicks, Rodney J.; Callahan, Jason; Kron, Tomas; MacManus, Michael P.; Ball, David L.; Jackson, Price; Siva, Shankar

    2015-09-01

    Purpose: Measuring changes in lung perfusion resulting from radiation therapy dose requires registration of the functional imaging to the radiation therapy treatment planning scan. This study investigates registration accuracy and utility for positron emission tomography (PET)/computed tomography (CT) perfusion imaging in radiation therapy for non–small cell lung cancer. Methods: {sup 68}Ga 4-dimensional PET/CT ventilation-perfusion imaging was performed before, during, and after radiation therapy for 5 patients. Rigid registration and deformable image registration (DIR) using B-splines and Demons algorithms was performed with the CT data to obtain a deformation map between the functional images and planning CT. Contour propagation accuracy and correspondence of anatomic features were used to assess registration accuracy. Wilcoxon signed-rank test was used to determine statistical significance. Changes in lung perfusion resulting from radiation therapy dose were calculated for each registration method for each patient and averaged over all patients. Results: With B-splines/Demons DIR, median distance to agreement between lung contours reduced modestly by 0.9/1.1 mm, 1.3/1.6 mm, and 1.3/1.6 mm for pretreatment, midtreatment, and posttreatment (P<.01 for all), and median Dice score between lung contours improved by 0.04/0.04, 0.05/0.05, and 0.05/0.05 for pretreatment, midtreatment, and posttreatment (P<.001 for all). Distance between anatomic features reduced with DIR by median 2.5 mm and 2.8 for pretreatment and midtreatment time points, respectively (P=.001) and 1.4 mm for posttreatment (P>.2). Poorer posttreatment results were likely caused by posttreatment pneumonitis and tumor regression. Up to 80% standardized uptake value loss in perfusion scans was observed. There was limited change in the loss in lung perfusion between registration methods; however, Demons resulted in larger interpatient variation compared with rigid and B-splines registration

  8. Lung hypoplasia in newborn rabbits with a diaphragmatic hernia affects pulmonary ventilation but not perfusion.

    PubMed

    Flemmer, Andreas W; Thio, Marta; Wallace, Megan J; Lee, Katie; Kitchen, Marcus J; Kerr, Lauren; Roehr, Charles C; Fouras, Andreas; Carnibella, Richard; Jani, Jaccques C; DeKoninck, Philip; Te Pas, Arjan B; Pearson, James T; Hooper, Stuart B

    2017-09-01

    BackgroundA congenital diaphragmatic hernia (DH) can result in severe lung hypoplasia that increases the risk of morbidity and mortality after birth; however, little is known about the cardiorespiratory transition at birth.MethodsUsing phase-contrast X-ray imaging and angiography, we examined the cardiorespiratory transition at birth in rabbit kittens with DHs. Surgery was performed on pregnant New Zealand white rabbits (n=18) at 25 days' gestation to induce a left-sided DH. Kittens were delivered at 30 days' gestation, intubated, and ventilated to achieve a tidal volume (Vt) of 8 ml/kg in control and 4 ml/kg in DH kittens while they were imaged.ResultsFunctional residual capacity (FRC) recruitment and Vt in the hypoplastic left lung were markedly reduced, resulting in a disproportionate distribution of FRC into the right lung. Following lung aeration, relative pulmonary blood flow (PBF) increased equally in both lungs, and the increase in pulmonary venous return was similar in both control and DH kittens.ConclusionThese findings indicate that nonuniform lung hypoplasia caused by DH alters the distribution of ventilation away from hypoplastic and into normally grown lung regions. During transition, the increase in PBF and pulmonary venous return, which is vital for maintaining cardiac output, is not affected by lung hypoplasia.

  9. Significance of single ventilation/perfusion mismatches in krypton-81m/technetium-99m lung scintigraphy

    SciTech Connect

    Rosen, J.M.; Palestro, C.J.; Markowitz, D.; Alderson, P.O.

    1986-03-01

    The significance of a single area of ventilation/perfusion (V/P) mismatch in lung scans performed on patients suspected of pulmonary embolism (PE) was evaluated. Ten of 20 patients with this scan finding were found to have PE. An intermediate probability of PE was found with segmental (71%) or subsegmental (45%) single V/P mismatches. Seven of 16 patients with a single V/P mismatch and without a matching radiographic opacity had PE. Three of the four patients who had a V/P mismatch and a matching radiographic opacity were found to have PE. Multiview ventilation imaging with 81mKr was found to have advantages for the evaluation of single V/P mismatches. Based on the data available at this time, a single V/P mismatch suggests an intermediate probability of PE.

  10. Assessment of branch pulmonary artery stenosis in children after repair of tetralogy of Fallot using lung perfusion scintigraphy comparison with echocardiography.

    PubMed

    Chien, Kuang-Jen; Huang, Hurng-Wern; Huang, Ta-Cheng; Lee, Cheng-Liang; Weng, Ken-Pen; Lin, Chu-Chuan; Shieh, Po-Chuen; Wu, Ming-Ting; Hsieh, Kai-Sheng

    2016-01-01

    The aim of this study was to compare the usefulness of lung perfusion scintigraphy and echocardiogram in the evaluation of the branch pulmonary arteries stenosis in children with tetralogy of Fallot (TOF). From February 2006 to November 2008, 74 children (mean age 7.8 years, range 1–18 years) who underwent repair of TOF at ages from 10 months to 13 years were suspected to have unilateral or bilateral branch pulmonary artery stenosis. In all patients, cardiac angiography was performed to confirm the diagnosis of branch pulmonary artery stenosis. Lung perfusion scintigraphy and two-dimensional transthoracic echocardiography were performed in all patients to compare their abilities to diagnose branch pulmonary artery stenosis. Of the 74 patients, 51 cases were found to have branch pulmonary artery stenosis by cardiac angiography. There was agreement between the scintigraphic and angiographic findings in 44 (86%) patients and there were discrepancies in 11 (15%) patients. The positive predictive value of our lung perfusion scintigraphy in detecting the branch pulmonary artery stenosis was 92 %. The positive and negative likelihood ratios of lung perfusion scintigraphy were 4.96 and 0.17, respectively. There was conformity between the echocardiographic and angiographic findings in 40 (78%) patients with discrepancies in 16 (21%) patients. The positive predictive value of our echocardiography in detecting the branch pulmonary artery stenosis was 89%. The positive and negative likelihood ratios of echocardiography were 3.61 and 0.28, respectively. Lung perfusion scintigraphy is a valuable, non-invasive screening tool in the assessment of branch pulmonary artery stenosis in children after TOF.

  11. Comparative imaging of differential pulmonary blood flow in patients with congenital heart disease: magnetic resonance imaging versus lung perfusion scintigraphy.

    PubMed

    Roman, Kevin S; Kellenberger, Christian J; Farooq, Saqba; MacGowan, Christopher K; Gilday, David L; Yoo, Shi-Joon

    2005-03-01

    Lung perfusion scintigraphy is considered the gold standard to assess differential pulmonary blood flow while magnetic resonance (MR) has been shown to be an accurate alternative in some studies. The purpose of the study was to assess the accuracy of phase contrast magnetic resonance (PC-MR) in measuring pulmonary blood flow ratio compared with lung perfusion scintigraphy in patients with complex pulmonary artery anatomy or pulmonary hypertension and to document reasons for discrepant results. We identified 25 cases of congenital heart disease between January 2000 and 2003, in whom both techniques of assessing pulmonary blood flow were performed within a 6-month period without an interim surgical or transcatheter intervention. The study group included cases with branch pulmonary artery stenosis, intracardiac shunts, single ventricle circulation, pulmonary venous anomalies and conotruncal defects. The mean age at study was 5.7 years (range 0.33-12) with a mean weight of 20.3 kg (range 6.5-53.6). The two methods were compared using a Bland-Altman analysis, and the Pearson correlation coefficient was calculated using the lung scan as the gold standard. Discrepant results were examined by reviewing the source images to elucidate reasons for error by MR. Bland-Altman analysis comparing right pulmonary artery (RPA) blood flow percentage, as measured by each modality, showed a mean difference of 1.43+/-9.8 (95% limits of agreement: -17.8, 20.6) with a correlation coefficient of r=0.84, P<0.0001. In six (24%) cases a large difference (>10%) was found with a mean difference between techniques of 17.9%. The reasons for discrepant results included MR artifacts, dephasing owing to turbulent flow, site of data acquisition and lobar lung collapse. When using PC-MR to assess pulmonary blood flow ratio, important technical errors occur in a significant proportion of patients who have abnormal pulmonary artery anatomy or pulmonary hypertension. If these technical errors are avoided

  12. Clinical outcomes of cytoreductive surgery combined with intrapleural perfusion of hyperthermic chemotherapy in advanced lung adenocarcinoma with pleural dissemination

    PubMed Central

    Yi, Eunjue; Kim, Daejoong; Cho, Sukki; Kim, Kwhanmien

    2016-01-01

    Background This study aimed to investigate the safety and feasibility of intrapleural perfusion hyperthermic chemotherapy (IPHC) followed by cytoreductive surgery as a part of multimodal strategy for the treatment of advanced lung adenocarcinoma. Methods Medical records of advanced lung cancer patients with pleural dissemination who underwent surgical treatment between 2003 and 2013 were reviewed retrospectively. Enrolled patients were divided into a surgery group comprising patients who underwent surgery only and an IPHC group, which consisted of patients who underwent surgery combined with IPHC. Results A total of 33 patients were enrolled in this study. Twenty-three patients underwent IPHC after surgical resection, and 10 patients underwent surgical resection only. The complication rate of the IPHC group was estimated to be 34.8% (8 cases), none of which included postoperative mortality. The complication rate of the surgery group was 40.0% (4 cases), which included one postoperative mortality. The 6-month, 1-year, and 3-year overall survival rates for the IPHC group were 95.7%, 91.3% and 38.6%, respectively, while those of the surgery group were 80.0%, 80.0% and 37.5%. The 6-month, 1-year and 3-year progression-free survival rates for the IPHC group were 87.0%, 47.8% and 24.3%, while those of surgery group were 44.4%, 33.3% and 0.0%, respectively. There were significant differences in overall survival rates between two groups (P=0.045); however, progression-free survival was not different between the two groups. Conclusions IPHC combined with cytoreductive surgery for advanced lung adenocarcinoma associated with pleural seeding could be performed safely and feasible. It would be part of multimodality therapy for certain category of advanced lung adenocarcinoma. However, the long-term benefits for survival is uncertain. More extensive and precisely designed studies are warranted to further evaluate the effectiveness of IPHC. PMID:27499943

  13. Insulin self-association: effects on lung disposition kinetics in the airways of the isolated perfused rat lung (IPRL).

    PubMed

    Pang, Yinuo; Sakagami, Masahiro; Byron, Peter R

    2007-09-01

    To characterize the kinetic dependence of pulmonary absorption and metabolism of insulin and lispro on the magnitude of their hexameric association. Hexamer content by weight percent (%Hex) in various insulin-zinc and lispro-zinc solutions were determined by quantitative centrifugal ultrafiltration and zinc titration with terpyridine (QCUF-ZTT). Each of the solutions (0.1 ml) was then administered into the airways of the IPRL of normal and experimental diabetic animals. Rate constants were determined for lung absorption (k (a)) and non-absorptive loss (k (nal); comprising mucociliary clearance and metabolism). %Hex in administered solutions ranged from 3.3 to 94.4%. Data analysis showed excellent correlations between the values for k (a) or k (nal) and %Hex, irrespective of insulin type, concentration, solution pH or ionic strength. The values for k (a) decreased (0.22 --> 0.05 h(-1)) with increasing %Hex, as did values for k (nal). At %Hex in administered solutions >/=50%, values for k (nal) approached estimates for the rate constant for mucociliary clearance, implying that lung metabolism occurred primarily with monomeric insulin. There were no differences in insulin disposition kinetics between lungs taken from experimental diabetic and sham-control animals. The kinetics of pulmonary insulin disposition depended on the magnitude of molecular self-association. Dissociated forms of insulin (dimers or monomers) in the dosing solution showed higher rates than hexamers for both lung absorption and metabolism.

  14. Role of Transient Receptor Potential Vanilloid 4 in Neutrophil Activation and Acute Lung Injury.

    PubMed

    Yin, Jun; Michalick, Laura; Tang, Christine; Tabuchi, Arata; Goldenberg, Neil; Dan, Qinghong; Awwad, Khader; Wang, Liming; Erfinanda, Lasti; Nouailles, Geraldine; Witzenrath, Martin; Vogelzang, Alexis; Lv, Lu; Lee, Warren L; Zhang, Haibo; Rotstein, Ori; Kapus, Andras; Szaszi, Katalin; Fleming, Ingrid; Liedtke, Wolfgang B; Kuppe, Hermann; Kuebler, Wolfgang M

    2016-03-01

    The cation channel transient receptor potential vanilloid (TRPV) 4 is expressed in endothelial and immune cells; however, its role in acute lung injury (ALI) is unclear. The functional relevance of TRPV4 was assessed in vivo, in isolated murine lungs, and in isolated neutrophils. Genetic deficiency of TRPV4 attenuated the functional, histological, and inflammatory hallmarks of acid-induced ALI. Similar protection was obtained with prophylactic administration of the TRPV4 inhibitor, GSK2193874; however, therapeutic administration of the TRPV4 inhibitor, HC-067047, after ALI induction had no beneficial effect. In isolated lungs, platelet-activating factor (PAF) increased vascular permeability in lungs perfused with trpv4(+/+) more than with trpv4(-/-) blood, independent of lung genotype, suggesting a contribution of TRPV4 on blood cells to lung vascular barrier failure. In neutrophils, TRPV4 inhibition or deficiency attenuated the PAF-induced increase in intracellular calcium. PAF induced formation of epoxyeicosatrienoic acids by neutrophils, which, in turn, stimulated TRPV4-dependent Ca(2+) signaling, whereas inhibition of epoxyeicosatrienoic acid formation inhibited the Ca(2+) response to PAF. TRPV4 deficiency prevented neutrophil responses to proinflammatory stimuli, including the formation of reactive oxygen species, neutrophil adhesion, and chemotaxis, putatively due to reduced activation of Rac. In chimeric mice, however, the majority of protective effects in acid-induced ALI were attributable to genetic deficiency of TRPV4 in parenchymal tissue, whereas TRPV4 deficiency in circulating blood cells primarily reduced lung myeloperoxidase activity. Our findings identify TRPV4 as novel regulator of neutrophil activation and suggest contributions of both parenchymal and neutrophilic TRPV4 in the pathophysiology of ALI.

  15. Physiologic significance of the phosphorylation potential in isolated perfused rat hearts (/sup 31/P NMR)

    SciTech Connect

    Watters, T.; Wikman-Coffelt, J.; Wu, S.; Wendland, M.; James, T.; Sievers, R.; Botvinick, E.; Parmley, W.

    1986-03-05

    The authors assessed the metabolic and mechanical effects of changes in coronary perfusion pressure (CPP) and afterload (A) in isolated working apex-ejecting rat hearts perfused with Krebs-Henseleit solution containing an excess of O/sub 2/ and substrate. Log(phosphorylation potential) or log (ATP)/(ADP)x (Pi), designated (L), and log (PCR)/(Pi), designated (L*), were calculated from HPLC measurements after rapid freeze-clamping. Increasing CPP from 80-140 cm H/sub 2/O caused an increase in coronary flow(flow), developed pressure(DevP), O/sub 2/ consumption (VO/sub 2/), L, L*, and CO. L and L* were directly related to VO/sub 2/ and CO. Increasing A from 80-140 cm H/sub 2/O caused an increase in DevP and VO/sub 2/, but a decrease in L, L*, and CO. L and L* were inversely linearly related to VO/sub 2/ but were directly linearly related to CO. In both experiments, L and L* are directly related to CO, suggesting that determination of L* (which can be done with /sup 31/P NMR spectroscopy) may be a useful non-invasive method for determining cardiac pump function curves. L and L* may be related to the Frank-Starling mechanism. In a separate experiment using /sup 31/P NMR spectroscopy of isovolumic (left ventricular balloon) perfused rat hearts, increasing CPP caused a direct linear increase in flow, DevP, and L*, confirming the L* results reported above with CPP experiments using the rapid freeze-clamp technique.

  16. Physiologic significance of the phosphorylation potential in isolated perfused rat hearts (31-P NMR)

    SciTech Connect

    Watters, T.; Wikman-Coffelt, J.; Wu, S.; Wendland, M.; James, T.; Sievers, R.; Botvinick, E.; Parmley, W.

    1986-03-05

    The authors assessed the metabolic and mechanical effects of changes in coronary perfusion pressure (CPP) and afterload (A) in isolated working apex-ejecting rat hearts perfused with Krebs-Henseleit solution containing an excess of O/sub 2/ and substrate. Log (phosphorylation potential) or log (ATP)/(ADP)x (Pi), designated (L), and log (PCR)/(Pi), designated (L*), were calculated from HPLC measurements after rapid freeze-clamping. Increasing CPP from 80-140 cm H/sub 2/O caused an increase in coronary flow (flow), developed pressure (DevP), O/sub 2/ consumption (VO/sub 2/), L, L*, and CO. L and L* were directly related to VO/sub 2/ and CO. Increasing A from 80-140 cm H/sub 2/O caused an increase in DevP and VO/sub 2/, but a decrease in L, L*, and CO. L and L* were inversely linearly related to VO/sub 2/ but were directly linearly related to CO. In both experiments, L and L* are directly related to CO, suggesting that determination of L* (which can be done with 31-P NMR spectroscopy) may be a useful non-invasive method for determining cardiac pump function curves. L and L* may be related to the Frank-Starling mechanism. In a separate experiment using 31-P NMR spectroscopy of isovolumic (left ventricular balloon) perfused rat hearts, increasing CPP caused a direct linear increase in flow, DevP, and L*, confirming the L* results reported above with CPP experiments using the rapid freeze-clamp technique.

  17. Stanniocalcin-2 (STC2): A potential lung cancer biomarker promotes lung cancer metastasis and progression.

    PubMed

    Na, Sang-su; Aldonza, Mark Borris; Sung, Hye-Jin; Kim, Yong-In; Son, Yeon Sung; Cho, Sukki; Cho, Je-Yoel

    2015-06-01

    The homodimeric glycoprotein, stanniocalcin 2 (STC2) is previously known to be involved in the regulation of calcium and phosphate transport in the kidney and also reported to play multiple roles in several cancers. However, its function and clinical significance in lung cancer have never been reported and still remain uncertain. Here, we investigated the possibility of STC2 as a lung cancer biomarker and identified its potential role in lung cancer cell growth, metastasis and progression. Proteomic analysis of secretome of primary cultured lung cancer cells revealed higher expression of STC2 in cancers compared to that of adjacent normal cells. RT-PCR and Western blot analyses showed higher mRNA and protein expressions of STC2 in lung cancer tissues compared to the adjacent normal tissues. Knockdown of STC2 in H460 lung cancer cells slowed down cell growth progression and colony formation. Further analysis revealed suppression of migration, invasion and delayed G0/G1 cell cycle progression in the STC2 knockdown cells. STC2 knockdown also attenuated the H202-induced oxidative stress on H460 cell viability with a subsequent increase in intracellular ROS levels, which suggest a protective role of STC2 in redox regulatory system of lung cancer. These findings suggest that STC2 can be a potential lung cancer biomarker and plays a positive role in lung cancer metastasis and progression. This article is part of a Special Issue entitled: Medical Proteomics. Copyright © 2015. Published by Elsevier B.V.

  18. Ventilation-perfusion relationships in the lung during head-out water immersion

    NASA Technical Reports Server (NTRS)

    Derion, Toniann; Guy, Harold J. B.; Tsukimoto, Koichi; Schaffartzik, Walter; Prediletto, Renato; Poole, David C.; Knight, Douglas R.; Wagner, Peter D.

    1992-01-01

    Mechanisms of altered pulmonary gas exchange during water immersion were studied in 12 normal males: 6 young (aged 20-29) and 6 older (aged 40-45). It is concluded that, in young subjects with closing volume (CV) less than expiratory reserve volume (ERV), gas exchange was enhanced during immersion, because normal ventilation-perfusion relations were preserved, and by mass balance, the ventilation/O2 uptake changes elevated arterial P(O2). In older males with CV greater than ERV and 52 percent of tidal volume below CV, immersion-induced airways closure during tidal breathing was associated with minimally increased shunt that did not significantly impair gas exchange. It is suggested that airways closure of this degree is of little importance to gas exchange.

  19. Ventilation-perfusion relationships in the lung during head-out water immersion

    NASA Technical Reports Server (NTRS)

    Derion, Toniann; Guy, Harold J. B.; Tsukimoto, Koichi; Schaffartzik, Walter; Prediletto, Renato; Poole, David C.; Knight, Douglas R.; Wagner, Peter D.

    1992-01-01

    Mechanisms of altered pulmonary gas exchange during water immersion were studied in 12 normal males: 6 young (aged 20-29) and 6 older (aged 40-45). It is concluded that, in young subjects with closing volume (CV) less than expiratory reserve volume (ERV), gas exchange was enhanced during immersion, because normal ventilation-perfusion relations were preserved, and by mass balance, the ventilation/O2 uptake changes elevated arterial P(O2). In older males with CV greater than ERV and 52 percent of tidal volume below CV, immersion-induced airways closure during tidal breathing was associated with minimally increased shunt that did not significantly impair gas exchange. It is suggested that airways closure of this degree is of little importance to gas exchange.

  20. Analysis of Contrast-Enhanced Ultrasound Perfusion Patterns and Time-Intensity Curves for Metastatic Lymph Nodes From Lung Cancer: Preliminary Results.

    PubMed

    Yin, Shanshan; Cui, Qiuli; Wang, Song; Fan, Zhihui; Yan, Kun

    2017-09-06

    To retrospectively summarize the similarities and differences in contrast-enhanced ultrasound (US) findings for lymph node metastasis from adenocarcinoma, squamous carcinoma, and small cell lung cancer. Patients who had received contrast-enhanced US examinations and had a histologic diagnosis of supraclavicular lymph node metastasis from lung cancer were included. The perfusion patterns on contrast-enhanced US images and time-intensity curve parameters were analyzed for the different pathologic types. The microvascular density and microvascular diameter were evaluated. Totally, 61 patients were enrolled in this study, including 26 cases with lung squamous carcinoma, 26 with lung adenocarcinoma, and 9 with small cell lung cancer. Contrast-enhanced US perfusion showed no significant differences in enhancement uniformity during the arterial phase and in the presence of unenhanced areas of metastatic lymph nodes with the 3 different pathologic origins (P > .05), but fewer unenhanced areas could be seen in metastatic lymph nodes from adenocarcinoma. The analysis of the time-intensity curve parameters showed that there were significant differences in the peak intensity between metastatic lymph nodes from lung squamous carcinoma and lung adenocarcinoma (P < .05). The microvascular density of metastatic lymph nodes from adenocarcinoma was significantly higher than that of metastatic lymph nodes from squamous carcinoma and small cell lung cancer (P < .001; P = .0444), whereas the microvascular diameter of metastatic lymph nodes from adenocarcinoma was significantly smaller than that from squamous carcinoma and small cell lung cancer (P = .0277; P < .001). Effects of the pathologic diagnosis should be considered when analyzing quantitative parameters of metastatic lymph nodes during contrast-enhanced US examinations, even in the same organ. © 2017 by the American Institute of Ultrasound in Medicine.

  1. Depleted energy charge and increased pulmonary endothelial permeability induced by mitochondrial complex I inhibition are mitigated by coenzyme Q1 in the isolated perfused rat lung

    PubMed Central

    Bongard, Robert D.; Yan, Ke; Hoffmann, Raymond G.; Audi, Said H.; Zhang, Xiao; Lindemer, Brian J.; Townsley, Mary I.; Merker, Marilyn P.

    2013-01-01

    Mitochondrial dysfunction is associated with various forms of lung injury and disease that also involve alterations in pulmonary endothelial permeability, but the relationship, if any, between the two is not well understood. This question was addressed by perfusing the isolated intact rat lung with a buffered physiological saline solution in the absence or presence of the mitochondrial complex I inhibitor rotenone (20 uM). As compared to control, rotenone depressed whole lung tissue ATP from 5.66 ± 0.46 (SEM) to 2.34 ± 0.15 (SEM) μmol·gram−1 dry lung, with concomitant increases in the ADP:ATP and AMP:ATP ratios. Rotenone also increased lung perfusate lactate (from 12.36 ± 1.64 (SEM) to 38.62 ± 3.14 μmol·15 min−1 perfusion·gm−1 dry lung) and the lactate:pyruvate ratio, but had no detectable impact on lung tissue GSH:GSSG redox status. The amphipathic quinone, coenzyme Q1 (CoQ1; 50 μM) mitigated the impact of rotenone on the adenine nucleotide balance, wherein mitigation was blocked by NAD(P)H:quinone oxidoreductase 1 (NQO1) or mitochondrial complex III inhibitors. In separate studies, rotenone increased the pulmonary vascular endothelial filtration coefficient (Kf) from 0.043 ± 0.010 (SEM) to 0.156 ± 0.037 (SEM) ml·min−1·cm H2O−1·gm−1 dry lung weight, and CoQ1 protected against the effect of rotenone on Kf. A second complex I inhibitor, piericidin A, qualitatively reproduced the impact of rotenone on Kf and the lactate/pyruvate ratio. Taken together, the observations imply that pulmonary endothelial barrier integrity depends on mitochondrial bioenergetics as reflected in lung tissue ATP levels and that compensatory activation of whole lung glycolysis cannot protect against pulmonary endothelial hyperpermeability in response to mitochondrial blockade. The study further suggests that low molecular weight amphipathic quinones may have therapeutic utility in protecting lung barrier function in mitochondrial insufficiency. PMID:23912160

  2. Depleted energy charge and increased pulmonary endothelial permeability induced by mitochondrial complex I inhibition are mitigated by coenzyme Q1 in the isolated perfused rat lung.

    PubMed

    Bongard, Robert D; Yan, Ke; Hoffmann, Raymond G; Audi, Said H; Zhang, Xiao; Lindemer, Brian J; Townsley, Mary I; Merker, Marilyn P

    2013-12-01

    Mitochondrial dysfunction is associated with various forms of lung injury and disease that also involve alterations in pulmonary endothelial permeability, but the relationship, if any, between the two is not well understood. This question was addressed by perfusing isolated intact rat lung with a buffered physiological saline solution in the absence or presence of the mitochondrial complex I inhibitor rotenone (20 μM). Compared to control, rotenone depressed whole lung tissue ATP from 5.66 ± 0.46 (SEM) to 2.34 ± 0.15 µmol · g(-1) dry lung, with concomitant increases in the ADP:ATP and AMP:ATP ratios. Rotenone also increased lung perfusate lactate (from 12.36 ± 1.64 to 38.62 ± 3.14 µmol · 15 min(-1) perfusion · g(-1) dry lung) and the lactate:pyruvate ratio, but had no detectable impact on lung tissue GSH:GSSG redox status. The amphipathic quinone coenzyme Q1 (CoQ1; 50 μM) mitigated the impact of rotenone on the adenine nucleotide balance, wherein mitigation was blocked by NAD(P)H-quinone oxidoreductase 1 or mitochondrial complex III inhibitors. In separate studies, rotenone increased the pulmonary vascular endothelial filtration coefficient (Kf) from 0.043 ± 0.010 to 0.156 ± 0.037 ml · min(-1) · cm H2O(-1) · g(-1) dry lung, and CoQ1 protected against the effect of rotenone on Kf. A second complex I inhibitor, piericidin A, qualitatively reproduced the impact of rotenone on Kf and the lactate:pyruvate ratio. Taken together, the observations imply that pulmonary endothelial barrier integrity depends on mitochondrial bioenergetics as reflected in lung tissue ATP levels and that compensatory activation of whole lung glycolysis cannot protect against pulmonary endothelial hyperpermeability in response to mitochondrial blockade. The study further suggests that low-molecular-weight amphipathic quinones may have therapeutic utility in protecting lung barrier function in mitochondrial insufficiency. Published by Elsevier Inc.

  3. Evaluation of residual functional lung volume on Tc-99m DTPA aerosol ventilation and Tc-99m MAA perfusion scintigraphy in primary ciliary dyskinesia (Kartagener syndrome).

    PubMed

    Chen, Yu-Wen; Chang, Chin-Chuan; Lai, Yung-Chuang; Lu, Chia-Ying; Dai, Zen-Kong

    2008-12-01

    Kartagener syndrome is diagnosed as sinusitis, bronchitis (bronchiectasis), and situs inversus by the clinical features. It is a subclass of primary ciliary dyskinesia (PCD) disease. A 12-year-old girl who had frequent upper and lower airway infections since birth, which was confirmed as Kartagener syndrome by HRCT imaging. We present the residual functional lung volume and mucociliary clearance findings seen on Tc-99m DTPA aerosol ventilation and Tc-99m MAA perfusion scintigraphy.

  4. [Effect of hypocapnia/alkalosis on the fluid filtration rate in isolated and perfused rabbit lungs].

    PubMed

    Urich, Daniela; Trejo, Humberto; Pezzulo, Alejandro; Caraballo, Juan Carlos; Gutiérrez, Jeydith; Castro, Ignacio; Sánchez-de León, Roberto

    2008-06-01

    Hypocapnia/alkalosis is a consequence of several lung and metabolic pathologies. The aim of this study was to determine whether the increase of fluid filtration rate (FFR) that occurs during Hypocapnia/alkalosis circumstances is determined by hypocapnia, alkalosis or both. 7 groups were formed (N=36) using isolated rabbit lungs. Group 1: Control (PCO2 6%, pH: 7.35-7.45); Group 2 (n=6): Hypocapnia/Alkalosis (CO2 1%, pH: 7.9); Group 3 (n=6): Hypocapnia/Normo-pH (CO2 1% pH 7.35-7.45), Group 4 (n=6) Normocapnia/Alcalosis (CO2 6%, pH: 7.9). Fenoterol, papaverine and hydrocortisone were added to Groups 5, 6 and 7 (n=4) respectively, all under Normocapnia/Alkalosis. FFR and Pulmonary Arterial Pressure (Pap) were considerably higher in group 2 than in control (FFR: 1.92g/min +/- 0.6 vs 0.0 g/min +/- 0.006). A strong influence exerted by pH was observed when Group 3 and group 4 were compared (FFR: 0.02 g/min +/- 0.009 vs 2.3 g/min +/- 0.9) and (Pap: 13.5 cmH2O +/- 1.4 vs 90 cmH2O +/- 15). A reduced effect was observed in groups 5 and 6 (papaverine and hydrocorisone) and a totally abolished effect was observed in group 7 (fenoterol) (FFR: 0.001 +/- 0.0003 mL/min and Pap: 14 +/- 0.8 cmH2O). Pulmonary edema induced by Hypocapnia/alkalosis is a consequence of alkalosis and not of hypocapnia. This effect could be due to inflammatory damage in the lung parenchyma and alkalosis-mediated vasoconstriction.

  5. Whole-tumour CT-perfusion of unresectable lung cancer for the monitoring of anti-angiogenetic chemotherapy effects.

    PubMed

    Fraioli, F; Anzidei, M; Serra, G; Liberali, S; Fiorelli, A; Zaccagna, F; Longo, F; Anile, M; Catalano, C

    2013-09-01

    To determine whether CT-perfusion (CT-p) can be used to evaluate the effects of chemotherapy and anti-angiogenic treatment in patients with non-small-cell lung carcinoma (NSCLC) and whether CT-p and standard therapeutic response assessment (RECIST) data obtained before and after therapy correlate. 55 patients with unresectable NSCLC underwent CT-p before the beginning of therapy and 50 of them repeated CT-p 90 days after it. Therapeutic protocol included platinum-based doublets plus bevacizumab for non-squamous carcinoma and platinum-based doublets for squamous carcinoma. RECIST measurements and calculations of blood flow (BF), blood volume (BV), time to peak (TTP) and permeability surface (PS) were performed, and baseline and post-treatment measurements were tested for statistically significant differences. Baseline and follow-up perfusion parameters were also compared based on histopathological subclassification (2004 World Health Organization Classification of Tumours) and therapy response assessed by RECIST. Tumour histology was consistent with large cell carcinoma in 14/50 (28%) cases, adenocarcinoma in 22/50 (44%) cases and squamous cell carcinoma in the remaining 14/50 (28%) cases. BF and PS differences for all tumours between baseline and post-therapy measurements were significant (p=0.001); no significant changes were found for BV (p=0.3) and TTP (p=0.1). The highest increase of BV was demonstrated in adenocarcinoma (5.2±34.1%), whereas the highest increase of TTP was shown in large cell carcinoma (6.9±22.4%), and the highest decrease of PS was shown in squamous cell carcinoma (-21.5±18.5%). A significant difference between the three histological subtypes was demonstrated only for BV (p<0.007). On the basis of RECIST criteria, 8 (16%) patients were classified as partial response (PR), 2 (4%) as progressive disease (PD) and the remaining 40 (80%) as stable disease (SD). Among PR, a decrease of both BF (18±9.6%) and BV (12.6±9.2%) were observed; TTP

  6. Whole-tumour CT-perfusion of unresectable lung cancer for the monitoring of anti-angiogenetic chemotherapy effects

    PubMed Central

    Anzidei, M; Serra, G; Liberali, S; Fiorelli, A; Zaccagna, F; Longo, F; Anile, M; Catalano, C

    2013-01-01

    Objective: To determine whether CT-perfusion (CT-p) can be used to evaluate the effects of chemotherapy and anti-angiogenic treatment in patients with non-small-cell lung carcinoma (NSCLC) and whether CT-p and standard therapeutic response assessment (RECIST) data obtained before and after therapy correlate. Methods: 55 patients with unresectable NSCLC underwent CT-p before the beginning of therapy and 50 of them repeated CT-p 90 days after it. Therapeutic protocol included platinum-based doublets plus bevacizumab for non-squamous carcinoma and platinum-based doublets for squamous carcinoma. RECIST measurements and calculations of blood flow (BF), blood volume (BV), time to peak (TTP) and permeability surface (PS) were performed, and baseline and post-treatment measurements were tested for statistically significant differences. Baseline and follow-up perfusion parameters were also compared based on histopathological subclassification (2004 World Health Organization Classification of Tumours) and therapy response assessed by RECIST. Results: Tumour histology was consistent with large cell carcinoma in 14/50 (28%) cases, adenocarcinoma in 22/50 (44%) cases and squamous cell carcinoma in the remaining 14/50 (28%) cases. BF and PS differences for all tumours between baseline and post-therapy measurements were significant (p=0.001); no significant changes were found for BV (p=0.3) and TTP (p=0.1). The highest increase of BV was demonstrated in adenocarcinoma (5.2±34.1%), whereas the highest increase of TTP was shown in large cell carcinoma (6.9±22.4%), and the highest decrease of PS was shown in squamous cell carcinoma (−21.5±18.5%). A significant difference between the three histological subtypes was demonstrated only for BV (p<0.007). On the basis of RECIST criteria, 8 (16%) patients were classified as partial response (PR), 2 (4%) as progressive disease (PD) and the remaining 40 (80%) as stable disease (SD). Among PR, a decrease of both BF (18±9.6%) and BV (12

  7. Evaluation of the preventive effect of dexpanthenol in radiation injury by lung perfusion scintigraphy: a preclinical experimental model of radiation injury.

    PubMed

    Koç, Zehra P; İn, Erdal; Karslioğlu, İhsan; Üçer, Özlem; Canpolat, Sinan

    2015-12-01

    The aim of this study was to show the preventative effects of dexpanthenol in radiation injuries caused by radiotherapy (RT) through the use of lung perfusion scintigraphy in the pre-RT and post-RT periods. Six male New Zealand rabbits (5-6 months of age and ∼2.5-3 kg in weight) were the used in this study. The animals were subjected to Tc-macroaggregated albumin lung perfusion scintigraphy in the pre-RT and post-RT (i.e. 2 weeks after treatment) periods. The scintigraphies were performed with the same dose by the same staff and the methodology used the same acquisition parameters. The rabbits were divided into two groups: group I (administered RT only) and group II (also administered intramuscular 500 mg dexpanthenol injections for 14 consecutive days after RT). Quantification was performed to compare the groups and the quantification variables were compared using a paired samples t-test, with P value less than 0.05 considered to be statistically significant. Histopathological analysis was also carried out. The post-RT scintigraphies indicated a decrease in the counts in both lungs, suggesting early post-RT injury. The difference between the counts obtained from both lungs in groups I and II was significantly different and favoured group II. Histopathological results confirmed the scintigraphy results. It is possible to estimate post-RT changes in the early period (in contrast to previous data) by lung perfusion scintigraphy. Dexpanthenol may also reduce the effects of RT to a degree. Although this is the first study to report the preventive effects of dexpanthenol on RT injuries, further studies are warranted in this area.

  8. [Quantitatively evaluating the evolution of the tumor perfusion in A549 lung adenocarcinoma transplantation model induced by antiangiogenic treatment].

    PubMed

    Xiong, Zeng; Deng, Pengbo; Hu, Chengping; Liu, Jinkang; Yang, Huaping; Zhou, Jianhua; Wang, Ying; Zhou, Hui; Zhu, Zhiming

    2016-01-26

    To quantitatively evaluate the evolution of the tumor perfusion in A549 lung adenocarcinoma transplantation model induced by antiangiogenic treatment. To establish the preclinical transplantation model of lung adenocarcinoma, 60 BALB/c nu/nu mice was inoculated with A549 cell lines via axilla. Sixty mice were randomly divided into 2 groups. The treatment group was treated with intravenous Bevacizumab (10 mg/kg weight, in a single injection), and the control group received saline only in the same dose. Five times of volume perfusion CT (VPCT) scan was performed before treatment, and on the second, forth, sixth and tenth days of treatment, respectively. The values of blood flow (BF) in the A549 tumors were measured after scanning. The microvessel density (MVD), vessel maturity index (VMI) in the tumors were determined using multiplexed QDs-based immunohistochemical staining. Comparing the values of BF, VMI and MVD between the two groups on the same day before treatment, the values of BF, VMI and MVD of the treatment group were (13.5±1.5) ml·(100 ml)(-1)·min(-1,) 0.14±0.04, (45.7±16.5)/HPF, respectively, and those in the control group were (13.4±1.6) ml·(100 ml)(-1)·min(-1) , 0.14±0.05, (48.0±7.0) /HPF , respectively. There was no significant difference between the two groups (all P>0.05). And on the second, forth, sixth, tenth days of treatment, the values of BF of the treatment group were (17.9±7.3), (32.2±6.9), (18.5±2.4) and (13.8±1.8) ml·(100 ml)(-1)·min(-1,) respectively, and those in the control group were (10.5±0.6), (9.6±0.8), (5.7±1.2) and (1.9±1.0) ml·(100 ml)(-1)·min(-1,) respectively. The values of VMI of the treatment group were 1.17±0.22, 3.25±0.23, 2.94±0.31 and 1.07±0.18, respectively, and those in the control group were 0.12±0.03, 0.13±0.03, 0.15±0.03, and 0.13±0.03, respectively. The values of MVD of the treatment group were (38.0±6.3), (24.3±5.4), (15.2±3.4) and (13.5±4.7)/HPF, respectively, and those in the

  9. Evaluation of (iodine-125)N,N,N'-trimethyl-N'-(2-hydroxy-3-methyl-5-iodobenzyl)-1,3- propanediamine lung uptake using an isolated-perfused lung model

    SciTech Connect

    Slosman, D.O.; Brill, A.B.; Polla, B.S.; Alderson, P.O.

    1987-02-01

    Lung uptake of N,N,N'-trimethyl-N'-(2-Hydroxy-3-methyl-5-iodobenzyl)-1,3- propanediamine (HIPDM) has been reported, but the mechanism of this process has not yet been established. Thus, single-pass (/sup 125/I)HIPDM accumulation was studied in rat lungs perfused with a Krebs-Ringer bicarbonate buffer containing 4.5% bovine albumin. Iodine-125 HIPDM lung accumulation was monitored by the percent of extraction per gram of lung tissue. Iodine-125 HIPDM lung uptake did not appear to occur by simple diffusion. As the time of perfusion was increased from 2 to 15 min, the rate of uptake of 2 microM (/sup 125/I)HIPDM decreased by 40%. During a 2-min perfusion, 98.6% +/- 6.7 (n = 8) extraction was observed with 2 microM (/sup 125/I)HIPDM, but only 38% +/- 2.0 (n = 3) was extracted when the (/sup 125/I)HIPDM concentration was 1 mM. The addition of 1 mM chlorpromazine, propranolol or imipramine also decreased (/sup 125/I)HIPDM lung uptake to 43.0% +/- 1.5, 51.4% +/- 2.2, and 49.8% +/- 0.8, respectively, (each n = 4 - 6, p less than 0.001). Cold (4 degrees C) had little effect on pulmonary accumulation (77.7% +/- 7.4, n = 5, p less than 0.01), and the addition of ouabain or the use of sodium-free medium had no effect. Thus, pulmonary (/sup 125/I)HIPDM accumulation does not appear to occur by sodium-dependent active transport. Rather, its uptake appears to be similar to the uptake of other basic amines, such as propranolol and imipramine, which are known to bind by physico-chemical interactions to pulmonary endothelial cell membranes and reflect pulmonary vascular surface area.

  10. Quality Improvement of Dual-Energy Lung Perfusion Image by Reduction of Low-Energy X-Ray Spectrum: An Evaluation on Clinical Images

    PubMed Central

    Kawai, Tatsuya; Ozawa, Yoshiyuki; Ogawa, Masaki; Ohashi, Kazuya; Suzuki, Kazushi; Shibamoto, Yuta

    2016-01-01

    Summary Background The effects of the reduction of low-energy X-ray spectrum on lung perfusion images created by dual-energy CT have not been well evaluated. The aim of this study is to investigate the reliability of lung perfusion blood volume (PBV) images created by dual-energy CT (DECT) equipped with or without a tin filter, focusing on its accuracy adjacent to high-attenuation areas. Material/Methods Among 176 patients who underwent DECT for suspicion of pulmonary embolism, 38 patients (mean age, 64; range, 16 to 83 years) without apparent evidence of pulmonary embolism were evaluated in this study. They underwent DECT at 100/140 kVp with a tin filter on 140 kVp tube (Group A; n=18) or at 80/140 kVp without the filter (Group B; n=20). On the lung PBV images, the degrees of artifacts – pulmonary enhancement defect (PED) and pseudo-enhancement in the trachea (PTE) adjacent to the vena cava were evaluated using a four-point scale (0=minimal to 3=prominent). Results The mean degrees of artifact in Group A were significantly lower than those in Group B (0.8 vs. 1.9; P<0.0001 for PED, respectively, and 1.1 vs. 2.2; P<0.0001 for TPE, respectively). The mean CTDIvols were 4.90±1.14 and 12.98±3.15 mGy (P<0.0001) for Group A and Group B, respectively. Conclusions The quality and accuracy of dual-energy lung perfusion image will be improved by using the tin filter technique. PMID:27994698

  11. Del-1 overexpression potentiates lung cancer cell proliferation and invasion

    SciTech Connect

    Lee, Seung-Hwan; Kim, Dong-Young; Jing, Feifeng; Kim, Hyesoon; Yun, Chae-Ok; Han, Deok-Jong; Choi, Eun Young

    2015-12-04

    Overexpression of the Del-1 gene potentiates proliferation and invasion of lung carcinoma cells. • Del-1 may be used as a diagnostic or prognostic marker for lung cancer progression.

  12. The added value of hybrid ventilation/perfusion SPECT/CT in patients with stable COPD or apparently healthy smokers. Cancer-suspected CT findings in the lungs are common when hybrid imaging is used

    PubMed Central

    Jögi, Jonas; Markstad, Hanna; Tufvesson, Ellen; Bjermer, Leif; Bajc, Marika

    2015-01-01

    Ventilation/perfusion (V/P) single-photon emission computed tomography (SPECT) is recognized as a diagnostic method with potential beyond the diagnosis of pulmonary embolism. V/P SPECT identifies functional impairment in diseases such as heart failure (HF), pneumonia, and chronic obstructive pulmonary disease (COPD). The development of hybrid SPECT/computed tomography (CT) systems, combining functional with morphological imaging through the addition of low-dose CT (LDCT), may be useful in COPD, as these patients are prone to lung cancer and other comorbidities. The aim of this study was to investigate the added value of LDCT among healthy smokers and patients with stable COPD, when examined with V/P SPECT/CT hybrid imaging. Sixty-nine subjects, 55 with COPD (GOLD I–IV) and 14 apparently healthy smokers, were examined with V/P SPECT and LDCT hybrid imaging. Spirometry was used to verify COPD grade. Only one apparently healthy smoker and three COPD patients had a normal or nearly normal V/P SPECT. All other patients showed various degrees of airway obstruction, even when spirometry was normal. The same interpretation was reached on both modalities in 39% of the patients. LDCT made V/P SPECT interpretation more certain in 9% of the patients and, in 52%, LDCT provided additional diagnoses. LDCT better characterized the type of emphysema in 12 patients. In 19 cases, tumor-suspected changes were reported. Three of these 19 patients (ie, 4.3% of all subjects) were in the end confirmed to have lung cancer. The majority of LDCT findings were not regarded as clinically significant. V/P SPECT identified perfusion patterns consistent with decompensated left ventricular HF in 14 COPD patients. In 16 patients (23%), perfusion defects were observed. HF and perfusion defects were not recognized with LDCT. In COPD patients and long-time smokers, hybrid imaging had added value compared to V/P SPECT alone, by identifying patients with lung malignancy and more clearly identifying

  13. The added value of hybrid ventilation/perfusion SPECT/CT in patients with stable COPD or apparently healthy smokers. Cancer-suspected CT findings in the lungs are common when hybrid imaging is used.

    PubMed

    Jögi, Jonas; Markstad, Hanna; Tufvesson, Ellen; Bjermer, Leif; Bajc, Marika

    2015-01-01

    Ventilation/perfusion (V/P) single-photon emission computed tomography (SPECT) is recognized as a diagnostic method with potential beyond the diagnosis of pulmonary embolism. V/P SPECT identifies functional impairment in diseases such as heart failure (HF), pneumonia, and chronic obstructive pulmonary disease (COPD). The development of hybrid SPECT/computed tomography (CT) systems, combining functional with morphological imaging through the addition of low-dose CT (LDCT), may be useful in COPD, as these patients are prone to lung cancer and other comorbidities. The aim of this study was to investigate the added value of LDCT among healthy smokers and patients with stable COPD, when examined with V/P SPECT/CT hybrid imaging. Sixty-nine subjects, 55 with COPD (GOLD I-IV) and 14 apparently healthy smokers, were examined with V/P SPECT and LDCT hybrid imaging. Spirometry was used to verify COPD grade. Only one apparently healthy smoker and three COPD patients had a normal or nearly normal V/P SPECT. All other patients showed various degrees of airway obstruction, even when spirometry was normal. The same interpretation was reached on both modalities in 39% of the patients. LDCT made V/P SPECT interpretation more certain in 9% of the patients and, in 52%, LDCT provided additional diagnoses. LDCT better characterized the type of emphysema in 12 patients. In 19 cases, tumor-suspected changes were reported. Three of these 19 patients (ie, 4.3% of all subjects) were in the end confirmed to have lung cancer. The majority of LDCT findings were not regarded as clinically significant. V/P SPECT identified perfusion patterns consistent with decompensated left ventricular HF in 14 COPD patients. In 16 patients (23%), perfusion defects were observed. HF and perfusion defects were not recognized with LDCT. In COPD patients and long-time smokers, hybrid imaging had added value compared to V/P SPECT alone, by identifying patients with lung malignancy and more clearly identifying

  14. Pressure and oxygen debt on bypass - potential quality markers of perfusion?

    PubMed

    Poullis, Mike; Palmer, K; Al-Rawi, O; Johnson, I; Ridgeway, T

    2012-05-01

    No markers of quality of perfusion pressure and oxygen delivery during cardiopulmonary bypass (CPB), to complement rewarming rate, maximum temperature on rewarming, lowest haematocrit, and blood glucose, exist. Using the electronic acquisition of blood pressure on bypass (JOCAP system), the percentage of time perfusion pressure was below 30, 40, 50, 60 and 70 mmHg, average deviance, confidence interval, median, mode, standard deviation, variance, and average, maximum and cumulative oxygen debt were calculated. Numerous different readouts of achievement of maintenance of constant pressure on bypass and oxygen debt are now easily achievable with perfusion electronic data management systems. Mean, median, and mode offer poor discrimination of pressure control during CPB. Percentage of time perfusion pressure was below 30, 40, 50, 60 and 70 mmHg, average deviance, confidence interval, and standard deviation all have discriminatory power, but need clinical correlation for their significance. A composite score involving non-pressure readouts (e.g. oxygen delivery, arterial and venous saturations, and flow rates) may need to be integrated into any perfusion quality marker. Assessment of adequacy of constant perfusion pressure and oxygen delivery may allow the scientific evaluation of pressure and oxygen delivery on bypass for patients to be compared accurately. Currently, in studies involving CPB, blood pressure targets are stated with no quantitative assessment of adequacy of achievement of these targets. Electronic data monitoring during cardiopulmonary bypass, when correlated with clinical outcome, may help to provide a marker of quality of perfusion pressure during CPB and may, indeed, allow patient-specific perfusion pressure strategies to be developed.

  15. Evaluation of mosaic pattern areas in HRCT with Min-IP reconstructions in patients with pulmonary hypertension: could this evaluation replace lung perfusion scintigraphy?

    PubMed

    Rossi, A; Attinà, D; Borgonovi, A; Buia, F; De Luca, F; Guidalotti, P L; Fughelli, P; Galiè, N; Zompatori, M

    2012-01-01

    The aim of this study is to evaluate a possible correlation between areas of lung attenuation, found in minimum intensity projection (Min-IP) reconstruction images performed with high resolution computed tomography without contrast medium (HRCT), and areas of lung perfusion alteration, found in lung perfusion scintigraphy (LPS). Two independent radiologists, unaware of LPS results, evaluated retrospectively a group of 113 patients affected by pulmonary hypertension (HP) of different aetiology. These have been examined in a period of two years in our centre both by spiral computed tomography (CT) with and without contrast-medium and by LPS. The final diagnosis was determined on clinical data, right heart catheterisation and contrast enhanced CT in angiographic phase (CTPA). We reconstructed the Min-IP images of lung parenchyma in all the cases both in HRCT without contrast-medium, and in contrast enhanced CT in angiographic phase (CTPA) in axial, sagittal and coronal planes. The obtained images were qualitatively graded into three categories of pulmonary attenuation: homogeneous, inhomogeneous with non-segmental patchy defects, inhomogeneous with segmental defects. The same criteria of classification were used also for LPS images. In the group of patients with chronic thromboembolic pulmonary hypertension (CTEPH) we also compared the number of areas of lung attenuation found in Min-IP images in HRCT without contrast-medium, and their exact localization, with not perfused areas in LPS. Gold standard for the diagnosis of pulmonary embolism was spiral contrast enhanced CT in angiographic phase (CTPA). In all cases we found exact correspondence between the Min-IP images in HRCT with and without contras agent. The attenuation pattern seen on Min-IP images was concordant with those of LPS in 96 out of 113 patients (85%). In the remaining 17 cases (15%) it was discordant: in 12 cases inhomogeneous in Min-IP images (7 with non-segmental patchy defects, 5 with segmental

  16. The potential value of tubal perfusion pressures measured during selective salpingography in predicting fertility.

    PubMed

    Papaioannou, Spyros; Afnan, Masoud; Girling, Alan J; Coomarasamy, Aravinthan; McHugo, Josephine M; Sharif, Khaldoun

    2003-02-01

    The value of tubal perfusion pressures assessed during selective salpingography and tubal catheterization in predicting fertility has not been investigated. A total of 325 infertile women underwent selective salpingography and tubal catheterization. Pregnancy information was collected in 256 (78.7%). The 50th (300 mmHg) and 90th (500 mmHg) centiles of the tubal perfusion pressure distribution in women with normal tubes on selective salpingography were used as thresholds. Women were divided into three tubal perfusion pressure groups: good (both tubes <300, or one tube <300 and the other 300-500 mmHg), mediocre (both tubes 300-500, or one tube <300 and the other >500 mmHg) and poor (both tubes >500, or one tube > 500 and the other 300-500 mmHg). The pregnancy rate in the good perfusion pressure group was significantly higher than that in the poor perfusion pressure group, both when all non-IVF/ICSI first conceptions (P = 0.001) as well as when spontaneous first conceptions only were considered (P = 0.010). The pregnancy rate in the mediocre group lay between the good and the poor groups, though none of the comparisons reached statistical significance. Selective salpingography can provide additional diagnostic information in comparison with other tubal assessment tests. Tubal perfusion pressures may be predictive of future fertility.

  17. (68)Ga-NOTA-CHSg and (99m)Tc-CHSg Labeled Microspheres for Lung Perfusion and Liver Radiomicrospheres Therapy Planning.

    PubMed

    Amor-Coarasa, Alejandro; Milera, Andrew; Carvajal, Denny; Gulec, Seza; Leichner, Jared; McGoron, Anthony J

    2013-01-01

    Fast biodegradable (12 h < half-life < 48 h) radioactive labeled microspheres are needed for PET and SPECT lung perfusion and radiomicrosphere therapy planning. An emulsion method was used to create 30.1 ±4.8  μ m size range microspheres with biodegradable Chitosan glycol (CHSg). Microspheres were characterized and labeled with (99m)Tc or (68)Ga as an alternative to MAA in perfusion PET and SPECT studies. Surface decoration of CHSg microspheres with p-SCN-Bn-NOTA was performed to increase (68)Ga  in vivo stability. (99m)Tc was labeled directly to the CHSg microspheres. Labeling yield and in vitro radiochemical stability were evaluated. In vitro CHSg microsphere degradation half-life was ~24 hours in porcine blood. Labeled microspheres were injected into Sprague Dawley rats and biodistribution was determined after 2 and 4 hours. Both (99m)Tc-CHSg and (68)Ga-NOTA-CHSg were quickly allocated in the lungs after injection. (99m)Tc-CHSg showed 91.6 ± 6.5% and 83.2 ± 4.1% of the decay corrected injected activity remaining in the lungs after 2 and 4 hours, respectively. For the obtained (68)Ga-NOTA-CHSg microspheres, lung allocation was very high with 98.9 ± 0.2% and 95.6 ± 0.9% after 2 and 4 hours, respectively. The addition of p-SCN-Bn-NOTA acts as a radioprotectant eliminating the released (68)Ga activity from the lungs to the bladder protecting the other organs.

  18. [Radionuclide evaluation of lung perfusion after transcatheter closure of patent ductus arteriosus: analysis of frequently used two different types of coils].

    PubMed

    Polat, Tuğçin Bora; Celebi, Ahmet; Hacımahmutoğlu, Sevim; Akdeniz, Celal; Erdem, Abdullah; Fırat, Fatih

    2011-05-01

    Impaired left lung perfusion (LLP) has been described after transcatheter closure of the patent ductus arteriosus (PDA). In this study, we aimed to evaluate lung perfusion scans (LPSs) following occlusion of PDA with two frequently used coils: Cook detachable coil and Gianturco coil. A prospective study of 89 patients who underwent PDA occlusion using the Cook coils in 49 and the Gianturco coils in 40, was conducted. LPSs were performed after a median period of 18 months. The relationships between the LPSs and continuous variables were assessed by Pearson correlation analysis and the cut-off value of the best correlated parameters to predict abnormal LPSs obtained by the Receiver Operating Characteristic (ROC) analysis. Decreased left lung perfusion (LLP) was found in 13 patients including 10 after using Cook coils and 3 after using Gianturco coils (p=0.077). LLP values were significantly correlated with the loops deployed at the pulmonary side, coil/ductal diameter ratio and number of coils deployed (p=0.002, p=0.006 and p=0.009, respectively). Number of loops deployed at the pulmonary side >1.4 (specificity 77%, sensitivity 85%, area under the ROC curve 0.804, 95%CI 0.661-0.947, p<0.001) and first coil/ductal diameter ratio >1.85 (specificity 70%, sensitivity 77%, area under the ROC curve 0.747, 95%CI 0.423-0.790, p<0.005) were the best discriminative cut-off values of decreased LLP. Impaired LLP may appear following transcatheter closure of PDA with either Cook detachable coils or Gianturco coils. This situation may be complicated with loops deployed at the pulmonary side, the use of relatively large size of coil with respect to the ductal diameter and the use of multiple coils.

  19. Prevalence of acute pulmonary embolism in central and subsegmental pulmonary arteries and relation to probability interpretation of ventilation/perfusion lung scans.

    PubMed

    Stein, P D; Henry, J W

    1997-05-01

    The purpose of this investigation is to determine the prevalence of acute pulmonary embolism (PE) limited to subsegmental pulmonary arteries. Contrast-enhanced helical (spiral) and electron-beam CT, in the hands of experienced radiologists who are skillful with this modality, are sensitive for the detection of acute PE in central pulmonary arteries, but have a low sensitivity for the detection of PE limited to subsegmental pulmonary arteries. The potential for CT to diagnose PE, therefore, is partially dependent on the prevalence of PE limited to subsegmental pulmonary arteries. Data are from the Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED). The largest pulmonary arteries that showed PE, as interpreted by the PIOPED angiographic readers, were identified in 375 patients in PIOPED with angiographically diagnosed PE. Among all patients with PE, 6% (95% confidence interval [CI], 4 to 9%) had PE limited to subsegmental branches of the pulmonary artery. Patients with high-probability ventilation/ perfusion (V/Q) scans had PE limited to subsegmental branches in only 1% (95% CI, 0 to 4%). Among patients with low-probability V/Q lung scans, 17% (95% CI, 8 to 29%) had PE limited to the subsegmental branches. Patients with low-probability V/Q scans and no prior cardiopulmonary disease had PE limited to the subsegmental pulmonary arteries in 30% (95% CI, 13 to 53%), whereas patients with low-probability V/Q scans who had prior cardiopulmonary disease had PE limited to subsegmental pulmonary arteries in 8% (95% CI, 2 to 22%) (p < 0.05). Based on data from all patients with PE in PIOPED, the prevalence of PE limited to subsegmental pulmonary arteries is low, 6%. PE limited to subsegmental pulmonary arteries was most prevalent among patients with low-probability V/Q scans, particularly if they had no prior cardiopulmonary disease.

  20. Effects of thermal degradation products from polyurethane foams based on toluene diisocyanate and diphenylmethane diisocyanate on isolated, perfused lung of guinea pig.

    PubMed

    Låstbom, Lena; Colmsjö, Anders; Johansson, Rolf; Karlsson, Daniel; Melin, Jens; Nordqvist, Yvonne; Skarping, Gunnar

    2003-04-01

    The composition of thermal degradation products from two types of polyurethane foams, one based on toluene diisocyanate (TDI) and the other on diphenylmethane diisocyanate (MDI), was analyzed and their toxic lung effects were compared. Isolated perfused lungs of guinea pig were subjected to thermal decomposition products of polyurethane foams from an aerosol generator with compartments for diluting, mixing, and sampling. Thermal degradation of MDI-based polyurethane foams released MDI, phenyl isocyanate, and methyl isocyanate. The emitted particulate fraction was 75% for MDI, whereas that for TDI from TDI-based polyurethane foam was 3%. Thermal degradation products from MDI-based foam caused a pronounced dose-dependent decrease in the measured lung function parameters (conductance and compliance). In contrast, the thermal degradation products from TDI-based foam did not cause any decrease in lung function. Thermal degradation products generated from MDI-based polyurethane foam were more toxic to the lung than those generated from TDI-based polyurethane foam. This difference was probable due to MDI in the particle phase.

  1. Ventilation/Perfusion SPECT lung scintigraphy and computed tomography pulmonary angiography in patients with clinical suspicion of pulmonary embolism.

    PubMed

    Ibáñez-Bravo, S; Banzo, I; Quirce, R; Martínez-Rodríguez, I; Jiménez-Bonilla, J; Martínez-Amador, N; Parra, J A; González-Macías, J; Carril, J M

    2016-01-01

    The aim was to compare ventilation/perfusion SPECT lung scintigraphy (V/Q-SPECT) and computed tomography pulmonary angiography (CTPA) in patients with suspicion of pulmonary embolism (PE). This prospectively designed study included 53 patients with intermediate or high clinical probability of PE. A V/Q-SPECT and CTPA was performed on all patients. The V/Q-SPECT was interpreted according to the European Association of Nuclear Medicine and Molecular Imaging (EANMMI) guidelines. CTPA was reported as positive, negative, or indeterminate. CTPA was positive in 22 cases, negative in 28, and indeterminate in 3. V/Q-SPECT was positive in 27 cases, negative in 24, and non-diagnostic in 2. In the 22 with positive CTPA, V/Q-SPECT was positive in 18, negative in 3, and non-diagnostic in 1. In the 28 with negative CTPA, V/Q-SPECT was positive in 8, negative in 19, and non-diagnostic in 1. In the 3 with indeterminate CTPA, V/Q-SPECT was positive in 1 and negative in 2. In the 2 non-diagnostic cases V/Q-SPECT, CTPA was positive in 1 and negative in one. In the 10 high clinical probabilities, CTPA and V/Q-SPECT were positive in 7, negative in 2, and in 1, CTPA was positive and V/Q-SPECT negative. In the 38 intermediate probability group, CTPA and V/Q-SPECT were positive in 11, negative in 17, with CTPA negative and V/Q-SPECT positive in 8, and in 2 CTPA was positive and V/Q-SPECT negative. The results show that V/Q-SPECT detected PE in 5 patients more than CTPA. Our results show a 77% concordance of both techniques. Overall V/Q-SPECT detected PE in 18% more patients than CTPA in the intermediate group. Both techniques have a complementary role when a diagnosis cannot be made with one of them. Copyright © 2016 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

  2. Predicting survival in potentially curable lung cancer patients.

    PubMed

    Win, Thida; Sharples, Linda; Groves, Ashley M; Ritchie, Andrew J; Wells, Francis C; Laroche, Clare M

    2008-01-01

    Lung cancer is the most common cause of cancer death with unchanged mortality for 50 years. Only localized nonsmall-cell lung cancer (NSCLC) is curable. In these patients it is essential to accurately predict survival to help identify those that will benefit from treatment and those at risk of relapse. Despite needing this clinical information, prospective data are lacking. We therefore prospectively identified prognostic factors in patients with potentially curable lung cancer. Over 2 years, 110 consecutive patients with confirmed localized NSCLC (stages 1-3A) were recruited from a single tertiary center. Prognostic factors investigated included age, gender, body mass index (BMI), performance status, comorbidity, disease stage, quality of life, and respiratory physiology. Patients were followed up for 3-5 years and mortality recorded. The data were analyzed using survival analysis methods. Twenty-eight patients died within 1 year, 15 patients died within 2 years, and 11 patients died within 3 years postsurgery. Kaplan-Meier survival estimates show a survival rate of 51% at 3 years. Factors significantly (p < 0.05) associated with poor overall survival were age at assessment, diabetes, serum albumin, peak VO(2) max, shuttle walk distance, and predicted postoperative transfer factor. In multiple-variable survival models, the strongest predictors of survival overall were diabetes and shuttle walk distance. The results show that potentially curable lung cancer patients should not be discriminated against with respect to weight and smoking history. Careful attention is required when managing patients with diabetes. Respiratory physiologic measurements were of limited value in predicting long-term survival after lung cancer surgery.

  3. A novel in vitro flat-bed perfusion biofilm model for determining the potential antimicrobial efficacy of topical wound treatments.

    PubMed

    Thorn, R M S; Greenman, J

    2009-12-01

    To develop an in vitro flat-bed perfusion biofilm model that could be used to determine the antimicrobial efficacy of topically applied treatments. Pseudomonas aeruginosa and Staphylococcus aureus biofilms were grown within continuously perfused cellulose matrices. Enumeration of the biofilm density and eluate was performed at various sampling times, enabling determination of the biofilm growth rate. Two antimicrobial wound dressings were applied to the surface of mature biofilms and periodically sampled. To enable real-time imaging of biofilm growth and potential antimicrobial kinetics, a bioluminescent Ps. aeruginosa biofilm was monitored using low-light photometry. Target species produced reproducible steady-state biofilms at a density of c. 10(7) per biofilm support matrix, after 24-h perfusion. Test dressings elicited significant antimicrobial effects, producing differing kill kinetic profiles. There was a good correlation between photon and viable count data. The model enables determination of the antimicrobial profile of topically applied treatments against target species biofilms, accurately differentiating bactericidal from bacteriostatic effects. Moreover, these effects could be monitored in real time using bioluminescence. This is the first in vitro biofilm model which can assess the antimicrobial potential of topical therapies in a dynamic growth environment.

  4. Perfusion decellularization of whole organs.

    PubMed

    Guyette, Jacques P; Gilpin, Sarah E; Charest, Jonathan M; Tapias, Luis F; Ren, Xi; Ott, Harald C

    2014-01-01

    The native extracellular matrix (ECM) outlines the architecture of organs and tissues. It provides a unique niche of composition and form, which serves as a foundational scaffold that supports organ-specific cell types and enables normal organ function. Here we describe a standard process for pressure-controlled perfusion decellularization of whole organs for generating acellular 3D scaffolds with preserved ECM protein content, architecture and perfusable vascular conduits. By applying antegrade perfusion of detergents and subsequent washes to arterial vasculature at low physiological pressures, successful decellularization of complex organs (i.e., hearts, lungs and kidneys) can be performed. By using appropriate modifications, pressure-controlled perfusion decellularization can be achieved in small-animal experimental models (rat organs, 4-5 d) and scaled to clinically relevant models (porcine and human organs, 12-14 d). Combining the unique structural and biochemical properties of native acellular scaffolds with subsequent recellularization techniques offers a novel platform for organ engineering and regeneration, for experimentation ex vivo and potential clinical application in vivo.

  5. [Outcome of patients with suspected pulmonary thromboembolism and low probability ventilation/perfusion lung scan who receive no long-term anticoagulation].

    PubMed

    Calvo Romero, J M; Arévalo Lorido, J C; Carretero Gómez, J

    2005-08-01

    To know in our area the security of no long-term anticoagulation in patients with suspected pulmonary thromboembolism (PTE) and a low probability ventilation/perfusion (V/Q) lung scan. Retrospective review of a series of consecutive outpatients with suspected PTE and a low probability V/Q lung scan, according to the modified PIOPED criteria, who receive no long-term anticoagulation. Among 38 patients with a low probability V/Q lung scan, 31 (81.6%) did not receive long-term anticoagulation. The median age was 69.1 years (range 26-88 years), and 19 (61.3%) were female. The clinical probability of PTE was moderate in 27 patients (87.1%). Twenty-two patients (71%) had a venous lower extremities echography-doppler negative for deep vein thrombosis (DVT). The median follow-up was 6.3 months (range 3-12 months). There was one case (3.2%; 95% confidence interval, 0.1-16.7%) with demonstrated PTE and DVT, and there was no death. No long-term anticoagulation in outpatients with a moderate clinical probability of PTE, a low probability V/Q lung scan and a venous lower extremities echography-doppler negative for DVT may be secure in our area.

  6. Perfusion parameters as potential imaging biomarkers for the early prediction of radiotherapy response in a rat tumor model

    PubMed Central

    Lee, Ho Yun; Kim, Namkug; Goo, Jin Mo; Chie, Eui Kyu; Song, Hye Jong

    2016-01-01

    percent change of uniformity in permeability and BV (r=0.202, r=0.644, and r=0.706, respectively). CONCLUSION By enabling earlier tumor response prediction than morphometric evaluation, the histogram analysis of CT perfusion parameters appears to have a potential in providing prognostic predictive information in an irradiated rat model. PMID:27023149

  7. Lymphangioleiomyomatosis Biomarkers Linked to Lung Metastatic Potential and Cell Stemness

    PubMed Central

    Ruiz de Garibay, Gorka; Herranz, Carmen; Llorente, Alicia; Boni, Jacopo; Serra-Musach, Jordi; Mateo, Francesca; Aguilar, Helena; Gómez-Baldó, Laia; Petit, Anna; Vidal, August; Climent, Fina; Hernández-Losa, Javier; Cordero, Álex; González-Suárez, Eva; Sánchez-Mut, José Vicente; Esteller, Manel; Llatjós, Roger; Varela, Mar; López, José Ignacio; García, Nadia; Extremera, Ana I.; Gumà, Anna; Ortega, Raúl; Plà, María Jesús; Fernández, Adela; Pernas, Sònia; Falo, Catalina; Morilla, Idoia; Campos, Miriam; Gil, Miguel; Román, Antonio; Molina-Molina, María; Ussetti, Piedad; Laporta, Rosalía; Valenzuela, Claudia; Ancochea, Julio; Xaubet, Antoni; Casanova, Álvaro; Pujana, Miguel Angel

    2015-01-01

    Lymphangioleiomyomatosis (LAM) is a rare lung-metastasizing neoplasm caused by the proliferation of smooth muscle-like cells that commonly carry loss-of-function mutations in either the tuberous sclerosis complex 1 or 2 (TSC1 or TSC2) genes. While allosteric inhibition of the mechanistic target of rapamycin (mTOR) has shown substantial clinical benefit, complementary therapies are required to improve response and/or to treat specific patients. However, there is a lack of LAM biomarkers that could potentially be used to monitor the disease and to develop other targeted therapies. We hypothesized that the mediators of cancer metastasis to lung, particularly in breast cancer, also play a relevant role in LAM. Analyses across independent breast cancer datasets revealed associations between low TSC1/2 expression, altered mTOR complex 1 (mTORC1) pathway signaling, and metastasis to lung. Subsequently, immunohistochemical analyses of 23 LAM lesions revealed positivity in all cases for the lung metastasis mediators fascin 1 (FSCN1) and inhibitor of DNA binding 1 (ID1). Moreover, assessment of breast cancer stem or luminal progenitor cell biomarkers showed positivity in most LAM tissue for the aldehyde dehydrogenase 1 (ALDH1), integrin-ß3 (ITGB3/CD61), and/or the sex-determining region Y-box 9 (SOX9) proteins. The immunohistochemical analyses also provided evidence of heterogeneity between and within LAM cases. The analysis of Tsc2-deficient cells revealed relative over-expression of FSCN1 and ID1; however, Tsc2-deficient cells did not show higher sensitivity to ID1-based cancer inhibitors. Collectively, the results of this study reveal novel LAM biomarkers linked to breast cancer metastasis to lung and to cell stemness, which in turn might guide the assessment of additional or complementary therapeutic opportunities for LAM. PMID:26167915

  8. [Effect of changes in airway pressure and the inspiratory volume on the fluid filtration rate and pulmonary artery pressure in isolated rabbit lungs perfused with blood and acellular solution].

    PubMed

    Crespo, Astrid; Novoa, Eva; Urich, Daniela; Trejo, Humberto; Pezzulo, Alejandro; Sznajder, Jacob I; Livia, Fernández; Sánchez-de León, Roberto

    2006-12-01

    It has been reported that ventilation with large tidal volumes causes pulmonary edema in rats by the stimulation and release of proinflammatory mediators. Our objective was to determine the level at which volutrauma induced by changes in Airway Pressure (PAW) and Inspiratory Volume (VI) produce significant changes on the Fluid Filtration Rate (FFR) and Pulmonary Artery Pressure (PAP) in lungs perfused with blood (cellular groups) or with a buffer-albumin solution (acellular groups), with a Positive End Expiratory Pressure (PEEP) 0 or 2 cmH2O and to study the effect of a vasodilator with antiinflammatory properties (fenoterol) in blood-perfused groups. Three experimental groups were used: the cellular groups studied the effect of increased PAW and IV in isolated lungs perfused with blood and PEEP 0 and 2; the acellular groups studied the increased PAW and IV in isolated lungs perfused with a buffer-albumin solution and PEEP 0 and 2; The fenoterol group studied the effect of increased PAW and IV in isolated lungs perfused with blood + fenoterol and PEEP 2. The results show that an increase of FFR is produced earlier in acellular groups than in cellular ones and that the damage in cellular groups is microscopically and macroscopically inferior when compared to acellular groups. Fenoterol did not inhibit edema formation, and that PEEP 2, both in the cellular and the acellular groups, has a protective effect. We propose the possible existence of mediators with protective effects against the formation of pulmonary edema in the blood. These data suggest that volutrauma induced pulmonary edema has a predominantly traumatic origin when the lungs are perfused with blood.

  9. Radon potential, geologic formations, and lung cancer risk

    PubMed Central

    Hahn, Ellen J.; Gokun, Yevgeniya; Andrews, William M.; Overfield, Bethany L.; Robertson, Heather; Wiggins, Amanda; Rayens, Mary Kay

    2015-01-01

    Objective Exposure to radon is associated with approximately 10% of U.S. lung cancer cases. Geologic rock units have varying concentrations of uranium, producing fluctuating amounts of radon. This exploratory study examined the spatial and statistical associations between radon values and geological formations to illustrate potential population-level lung cancer risk from radon exposure. Method This was a secondary data analysis of observed radon values collected in 1987 from homes (N = 309) in Kentucky and geologic rock formation data from the Kentucky Geological Survey. Radon value locations were plotted on digital geologic maps using ArcGIS and linked to specific geologic map units. Each map unit represented a package of different types of rock (e.g., limestone and/or shale). Log-transformed radon values and geologic formation categories were compared using one-way analysis of variance. Results Observed radon levels varied significantly by geologic formation category. Of the 14 geologic formation categories in north central Kentucky, four were associated with median radon levels, ranging from 8.10 to 2.75 pCi/L. Conclusion Radon potential maps that account for geologic factors and observed radon values may be superior to using observed radon values only. Knowing radon-prone areas could help target population-based lung cancer prevention interventions given the inequities that exist related to radon. PMID:26844090

  10. Endolymphatic perfusion with EGTA-acetoxymethyl ester inhibits asphyxia- and furosemide-induced decrease in endocochlear potential in guinea pigs.

    PubMed

    Mineharu, Akihito; Mori, Yoshiaki; Nimura, Yoshitsugu; Takamaki, Atsuko; Araki, Michitoshi; Yamaji, Junko; Yoshida, Ryotaro; Takenaka, Hiroshi; Kubota, Takahiro

    2005-02-01

    We examined the effect of the Ca(2+) concentration in the endolymph ([Ca](e)) or in the endolymphatic surface cells ([Ca](i)) on the endocochlear potential (EP) by using an endolymphatic or perilymphatic perfusion technique, respectively. (i) A large increase in [Ca](e) up to approximately 10(-3) M with a fall in the EP was induced by transient asphyxia ( approximately 2 min) or by the intravenous administration of furosemide (60 mg/kg), and a significant correlation was obtained between the EP and p[Ca](e) (= -log [Ca](e), r = 0.998). (ii) Perfusion of the endolymph with 10 mM EGTA for 5 min neither produced any significant change in the EP nor altered the asphyxia-induced change in EP (DeltaEP(asp)), suggesting that neither [Ca](e) nor the Ca(2+) concentration gradient across the stria vascularis contributed directly to the generation of the EP in the condition of low [Ca](e). In contrast, endolymphatic perfusion with high Ca(2+) (more than 10 mM) produced a decrease in EP and a significant correlation was obtained between the EP and the Ca(2+) concentration of perfusion solution (r = 0.982), suggesting that Ca(2+) permeability may exist across the stria vascularis. (iii) The administration of a Ca(2+) chelator, EGTA-acetoxymethyl ester (AM, 0.3 mM), to the endolymph, which produced a gradual increase in EP, suppressed significantly, by 60-80%, DeltaEP(asp) or furosemide-induced changes in EP. In contrast, perilymphatic administration of 0.5 mM EGTA-AM caused no significant suppression of the DeltaEP(asp). These findings suggest that [Ca](i) plays an important role in generating/maintaining a large positive EP.

  11. Risk of recurrence in patients with pulmonary embolism: predictive role of D-dimer and of residual perfusion defects on lung scintigraphy.

    PubMed

    Poli, Daniela; Cenci, Caterina; Antonucci, Emilia; Grifoni, Elisa; Arcangeli, Chiara; Prisco, Domenico; Abbate, Rosanna; Miniati, Massimo

    2013-02-01

    The stratification of recurrence risk after a first episode of venous thromboembolism (VTE) is an important topic of research, especially in patients with pulmonary embolism (PE). Elevated D-dimer levels and residual vein obstruction (RVO) at compression ultrasonography have been studied as predictors of recurrence after withdrawing oral anticoagulant treatment (OAT). It is still unknown if residual perfusion defects (PD) on lung scintigraphy are related to recurrent PE. In the present study, we evaluated the association of PD with PE recurrence. The relationship between PD, elevated D-dimer levels, and RVO was also investigated. We prospectively followed 236 consecutive patients who survived a first episode of objectively confirmed PE, with or without deep-vein thrombosis. After at least three months of OAT, treatment was withdrawn in 139 patients. D-dimer levels were evaluated at one month of OAT withdrawal, RVO was measured, and perfusion lung scan (P-scan) was performed to evaluate PD. During follow-up, 20 patients experienced a recurrent episode of VTE. Elevated D-dimer levels were significantly associated with VTE recurrence, (p=0.003). RVO was present in 22% of the patients with recurrence and in 7.5% of those without (p=0.07). No significant association was found between PD >10% and VTE recurrence, D-dimer, or RVO. In conclusion, we confirmed the positive predictive value of elevated D-dimer levels for recurrent VTE. Residual PD on lung scintigraphy are neither predictive of recurrence nor related to D-dimer levels or RVO.

  12. Extravasation from venous catheter: a serious complication potentially missed by lung imaging

    SciTech Connect

    Spicer, K.M.; Gordon, L.

    1983-11-01

    Three patients were referred for lung ventiliation and perfusion (V/Q) imaging with symptoms strongly suggestive of pulmonary embolus (PE). Chest roentgenograms and xenon ventilation studies on all three were normal, save for prominent mediastinal silhouettes and effusions. Technetium-99m macroaggregated albumin(Tc-99m MAA), when injected through the central venous catheter (CVP), revealed mediastinal localization, whereas antecubital injections showed normal pulmonary perfusion. Contrast fluoroscopy introduced through the venous catheter in the first patient defined the extravasation. For patients under strong suspicion of PE, with a venous catheter whose distal tip is seen about the level of the heart on chest radiograph, the authors recommend administering the perfusion agent slowly through the central catheter to exclude catheter-induced complications. When extravasation is detected, injection of Tc-99m MAA by peripheral vein should be used to exclude PE.

  13. Distribution of perfusion.

    PubMed

    Glenny, Robb; Robertson, H Thomas

    2011-01-01

    Local driving pressures and resistances within the pulmonary vascular tree determine the distribution of perfusion in the lung. Unlike other organs, these local determinants are significantly influenced by regional hydrostatic and alveolar pressures. Those effects on blood flow distribution are further magnified by the large vertical height of the human lung and the relatively low intravascular pressures in the pulmonary circulation. While the distribution of perfusion is largely due to passive determinants such as vascular geometry and hydrostatic pressures, active mechanisms such as vasoconstriction induced by local hypoxia can also redistribute blood flow. This chapter reviews the determinants of regional lung perfusion with a focus on vascular tree geometry, vertical gradients induced by gravity, the interactions between vascular and surrounding alveolar pressures, and hypoxic pulmonary vasoconstriction. While each of these determinants of perfusion distribution can be examined in isolation, the distribution of blood flow is dynamically determined and each component interacts with the others so that a change in one region of the lung influences the distribution of blood flow in other lung regions. © 2011 American Physiological Society.

  14. Changes in Global Function and Regional Ventilation and Perfusion on SPECT During the Course of Radiotherapy in Patients With Non-Small-Cell Lung Cancer

    SciTech Connect

    Yuan Shuanghu; Frey, Kirk A.; Gross, Milton D.; Hayman, James A.; Arenberg, Doug; Cai Xuwei; Ramnath, Nithya; Hassan, Khaled; Moran, Jean; Eisbruch, Avraham; Ten Haken, Randall K.; Kong Fengming

    2012-03-15

    Purpose: This study aimed to (1) examine changes in dyspnea, global pulmonary function test (PFT) results, and functional activity on ventilation (V)/perfusion (Q) single-photon emission computerized tomography (SPECT) scans during the course of radiation (RT), and (2) factors associated with the changes in patients with non-small-cell lung cancer (NSCLC). Methods and Materials: Fifty-six stage I to III NSCLC patients treated with definitive RT with or without chemotherapy were enrolled prospectively. Dyspnea was graded according to Common Terminology Criteria for Adverse Events version 3.0 prior to and weekly during RT. V/Q SPECT-computed tomography (CT) and PFTs were performed prior to and during RT at approximately 45 Gy. Functions of V and Q activities were assessed using a semiquantitative scoring of SPECT images. Results: Breathing improved significantly at the third week (mean dyspnea grade, 0.8 vs. 0.6; paired t-test p = 0.011) and worsened during the later course of RT (p > 0.05). Global PFT results did not change significantly, while regional lung function on V/Q SPECT improved significantly after {approx}45 Gy. The V defect score (DS) was 4.9 pre-RT versus 4.3 during RT (p = 0.01); Q DS was 4.3 pre-RT versus 4.0 during RT (p < 0.01). Improvements in V and Q functions were seen primarily in the ipsilateral lung (V DS, 1.9 pre-RT versus 1.4 during RT, p < 0.01; Q DS, 1.7 pre-RT versus 1.5 during RT, p < 0.01). Baseline primary tumor volume was significantly correlated with pre-RT V/Q DS (p < 0.01). Patients with central lung tumors had greater interval changes in V and Q than those with more peripheral tumors (p <0.05 for both V and Q DS). Conclusions: Regional ventilation and perfusion improved during RT at 45 Gy. This suggests that adaptive planning based on V/Q SPECT during RT may allow sparing of functionally recoverable lung tissue.

  15. Colony-stimulating factor 1 potentiates lung cancer bone metastasis.

    PubMed

    Hung, Jaclyn Y; Horn, Diane; Woodruff, Kathleen; Prihoda, Thomas; LeSaux, Claude; Peters, Jay; Tio, Fermin; Abboud-Werner, Sherry L

    2014-04-01

    Colony-stimulating factor 1 (CSF1) is essential for osteoclastogenesis that mediates osteolysis in metastatic tumors. Patients with lung cancer have increased CSF1 in serum and high levels are associated with poor survival. Adenocarcinomas metastasize rapidly and many patients suffer from bone metastasis. Lung cancer stem-like cells sustain tumor growth and potentiate metastasis. The purpose of this study was to determine the role of CSF1 in lung cancer bone metastasis and whether inhibition of CSF1 ameliorates the disease. Human lung adenocarcinoma A549 cells were examined in vitro for CSF1/CSF1R. A549-luc cells were injected intracardiac in NOD/SCID mice and metastasis was assessed. To determine the effect of CSF1 knockdown (KD) in A549 cells on bone metastasis, cells were stably transfected with a retroviral vector containing short-hairpin CSF1 (KD) or empty vector (CT). Results showed that A549 cells express CSF1/CSF1R; CSF1 increased their proliferation and invasion, whereas soluble CSF1R inhibited invasion. Mice injected with A549-luc cells showed osteolytic bone lesions 3.5 weeks after injection and lesions increased over 5 weeks. Tumors recapitulated adenocarcinoma morphology and showed osteoclasts along the tumor/bone interface, trabecular, and cortical bone loss. Analyses of KD cells showed decreased CSF1 protein levels, reduced colony formation in soft agar assay, and decreased fraction of stem-like cells. In CSF1KD mice, the incidence of tumor metastasis was similar to controls, although fewer CSF1KD mice had metastasis in both hind limbs. KD tumors showed reduced CSF1 expression, Ki-67+ cells, and osteoclasts. Importantly, there was a low incidence of large tumors >0.1 mm(2) in CSF1KD mice compared with control mice (10% vs 62.5%). This study established a lung osteolytic bone metastasis model that resembles human disease and suggests that CSF1 is a key determinant of cancer stem cell survival and tumor growth. Results may lead to novel strategies to

  16. Chronic hypoxia decreases arterial and venous compliance in isolated perfused rat lungs: an effect that is reversed by exogenous l-arginine

    PubMed Central

    Jin, Yi; Chen, Bernadette; Calvert, Thomas J.; Chicoine, Louis G.; Liu, Yusen

    2013-01-01

    Chronic hypoxia (CH)-induced pulmonary hypertension is characterized by vasoconstriction and vascular remodeling, leading to right ventricular dysfunction. Given the role of arterial compliance (Ca) in right ventricular work, a decrease in Ca would add to right ventricular work. Nitric oxide (NO) is a potent vasodilator made by NO synthases from l-arginine (l-Arg). However, little is known of the effect of l-Arg on vascular compliance (Cv) in the lung. We hypothesized that exposure to CH would decrease Ca and that this effect would be reversed by exogenous l-Arg. Sprague-Dawley rats were exposed to either normoxia or CH for 14 days; the lungs were then isolated and perfused. Vascular occlusions were performed and modeled using a three-compliance, two-resistor model. Pressure-flow curves were generated, and a distensible vessel model was used to estimate distensibility and a vascular resistance parameter (R0). Hypoxia resulted in the expected increase in arterial resistance (Ra) as well as a decrease in both Ca and Cv. l-Arg had little effect on Ra, Ca, or Cv in isolated lungs from normoxic animals. l-Arg decreased Ra in lungs from CH rats and redistributed compliance to approximately that found in normoxic lungs. CH increased R0, and l-Arg reversed this increase in R0. l-Arg increased exhaled NO, and inhibition of l-Arg uptake attenuated the l-Arg-induced increase in exhaled NO. These data demonstrate that the CH-induced decrease in Ca was reversed by l-Arg, suggesting that l-Arg may improve CH-induced right ventricular dysfunction. PMID:23103497

  17. Ventilation/perfusion SPECT in chronic obstructive pulmonary disease: an evaluation by reference to symptoms, spirometric lung function and emphysema, as assessed with HRCT.

    PubMed

    Jögi, Jonas; Ekberg, Marie; Jonson, Björn; Bozovic, Gracijela; Bajc, Marika

    2011-07-01

    Chronic obstructive pulmonary disease (COPD) is characterized by airflow limitation which is not fully reversible. Despite the heterogeneity of COPD, its diagnosis and staging is currently based solely on forced expiratory volume in 1 s (FEV(1)). FEV(1) does not explain the underlying pathophysiology of airflow limitation. The relationship between FEV(1), symptoms and emphysema extent is weak. Better diagnostic tools are needed to define COPD. Tomographic lung scintigraphy [ventilation/perfusion single photon emission tomography (V/P SPECT)] visualizes regional V and P. In COPD, relations between V/P SPECT, spirometry, high-resolution computed tomography (HRCT) and symptoms have been insufficiently studied. The aim of this study was to investigate how lung function imaging and obstructive disease grading undertaken using V/P SPECT correlate with symptoms, spirometric lung function and degree of emphysema assessed with HRCT in patients with COPD. Thirty patients with stable COPD were evaluated with the Medical Research Council dyspnoea questionnaire (MRC) and the clinical COPD questionnaire (CCQ). Spirometry was performed. The extent of emphysema was assessed using HRCT. V/P SPECT was used to assess V/P patterns, total reduction in lung function and degree of obstructive disease. The total reduction in lung function and degree of obstructive disease, assessed with V/P SPECT, significantly correlated with emphysema extent (r = 0.66-0.69, p < 0.0001) and spirometric lung function (r = 0.62-0.74, p < 0.0005). The correlation between emphysema extent and spirometric lung function was weaker. No correlation between MRC, CCQ and objective measurements was found. V/P SPECT is sensitive to early changes in COPD. V/P SPECT also has the possibility to identify comorbid disease. V/P SPECT findings show a significant correlation with emphysema extent and spirometric lung function. We therefore recommend that scintigraphic signs of COPD, whenever found, should be reported. V

  18. Is the predicted postoperative FEV1 estimated by planar lung perfusion scintigraphy accurate in patients undergoing pulmonary resection? Comparison of two processing methods.

    PubMed

    Caglar, Meltem; Kara, Murat; Aksoy, Tamer; Kiratli, Pinar Ozgen; Karabulut, Erdem; Dogan, Riza

    2010-07-01

    Estimation of postoperative forced expiratory volume in 1 s (FEV1) with radionuclide lung scintigraphy is frequently used to define functional operability in patients undergoing lung resection. We conducted a study to outline the reliability of planar quantitative lung perfusion scintigraphy (QLPS) with two different processing methods to estimate the postoperative lung function in patients with resectable lung disease. Forty-one patients with a mean age of 57 +/- 12 years who underwent either a pneumonectomy (n = 14) or a lobectomy (n = 27) were included in the study. QLPS with Tc-99m macroaggregated albumin was performed. Both three equal zones were generated for each lung [zone method (ZM)] and more precise regions of interest were drawn according to their anatomical shape in the anterior and posterior projections [lobe mapping method (LMM)] for each patient. The predicted postoperative (ppo) FEV1 values were compared with actual FEV1 values measured on postoperative day 1 (pod1 FEV1) and day 7 (pod 7 FEV1). The mean of preoperative FEV1 and ppoFEV1 values was 2.10 +/- 0.57 and 1.57 +/- 0.44 L, respectively. The mean of Pod1FEV1 (1.04 +/- 0.30 L) was lower than ppoFEV1 (p < 0.0001) but increased on day 7 (1.31 +/- 0.32 L) (p < 0.0001); however, it never reached the predicted values. Zone and LMMs estimated mean ppoFEV1 as 1.56 +/- 0.45 and 1.57 +/- 0.44 L, respectively. Both methods overestimated the actual value by 50% (ZM), 51% (LMM) and 19% (ZM), 20% (LMM) for pod 1 and pod 7, respectively. This overestimation was more pronounced in patients with chronic lung disease and hilar tumors. No significant differences were observed between ppoFEV1 values estimated by ZM or by LMM (p > 0.05). PpoFEV1 values predicted by both the zone and LMMs overestimated the actual measured lung volumes in patients undergoing pulmonary resection in the early postoperative period. LMM is not superior to ZM.

  19. Tomographic ventilation/perfusion lung scintigraphy in the monitoring of the effect of treatment in pulmonary embolism: serial follow-up over a 6-month period.

    PubMed

    Begic, Amela; Jögi, Jonas; Hadziredzepovic, Amra; Kucukalic-Selimović, Elma; Begovic-Hadzimuratovic, Sadzida; Bajc, Marika

    2011-06-01

    Pulmonary embolism (PE) is a severe condition with nonspecific symptoms. Diagnosis relies on medical imaging but follow-up is currently based on clinical symptoms and general risk factors. The duration of anticoagulant treatment after an acute episode of PE is still subject to debate and the best method of identifying the risk of recurrence in individual patients is undefined. Tomographic lung scintigraphy [ventilation/perfusion single photon emission computed tomography (V/P SPECT)] has improved the diagnostic accuracy with regard to PE but has not been evaluated for PE follow-up. The aim of this prospective study was to quantitatively follow the natural history of treated PE using V/P SPECT, which could prove helpful in defining an anticoagulant treatment regime for individual patients. Of 83 consecutive patients with clinically suspected PE examined with V/P SPECT, 23 patients with confirmed PE were followed by serial V/P SPECT examinations over a 6-month period. All patients were also followed clinically. The mean relative decrease in PE extent compared with the time of diagnosis was 54±26% at 2 weeks, 79±30% at 3 months, and 82±30% at 6 months. Significant resolution of mismatched perfusion defects occurred between V/P SPECT controls within the first 3 months of anticoagulation (P<0.001) but not thereafter. V/P SPECT identified four patients with chronic PE, even though all patients were free from symptoms at 3-month follow-up. Follow-up of PE with V/P SPECT is feasible to evaluate treatment effectiveness in individual patients and to identify patients that develop chronic PE. This study also confirms that resolution of perfusion defects after PE occurs within the first 3 months of treatment. It is therefore recommended that V/P SPECT follow-up should be considered at 3 months after diagnosis.

  20. Correlation between plasma brain natriuretic peptide concentration and lung thallium-201 uptake on exercise thallium perfusion images.

    PubMed

    Inoue, Noriko; Takahashi, Nobukazu; Kimura, Kazuo; Ishikawa, Toshiyuki; Toyama, Shinichi; Yoshii, Yuzuru; Uchino, Kazuaki; Yamakawa, Yohei; Matsumoto, Katsumi; Inoue, Tomio; Umemura, Satoshi

    2006-03-01

    The plasma brain natriuretic peptide (BNP) concentration at rest correlates with left ventricular end-diastolic pressure (LVEDP), left ventricular ejection fraction (LVEF), and pulmonary capillary wedge pressure (PCWP). High lung thallium-201 uptake has been reported to be associated with hemodynamic variables such as LVEDP, LVEF, and PCWP. However, there is no study that has investigated the correlation of plasma BNP concentration with lung thallium-201 uptake. We examined whether the plasma BNP concentration was related to lung thallium-201 uptake. Before exercise, venous blood samples were obtained from 39 patients with old myocardial infarction. We investigated the correlations between plasma BNP concentration and lung thallium-201 uptake, and whether they were related to LVEF, extent of nonviable myocardium, and ischemic myocardium, respectively, with thallium-201 exercise stress testing. The plasma BNP concentration significantly correlated with lung thallium-201 uptake (P < 0.05), nonviable segments (P < 0.01), and LVEF (P < 0.01). Lung thallium-201 uptake correlated with nonviable segments (P < 0.01). Our results suggest that increased secretion of BNP is related to increased lung thallium-201 uptake, and they are related to the extent of nonviable myocardium and decreased left ventricular function. Plasma BNP concentration and lung thalium-201 uptake may reflect the extent of myocardial fibrosis causing myocyte stretch.

  1. Synthesis of fluorine-18 labeled rhodamine B: A potential PET myocardial perfusion imaging agent

    PubMed Central

    Heinrich, Tobias K.; Gottumukkala, Vijay; Snay, Erin; Dunning, Patricia; Fahey, Frederic H; Treves, S. Ted; Packard, Alan B.

    2009-01-01

    There is considerable interest in developing an 18F-labeled PET myocardial perfusion agent. Rhodamine dyes share several properties with 99mTc-MIBI, the most commonly used single-photon myocardial perfusion agent, suggesting that an 18F-labeled rhodamine dye might prove useful for this application. In addition to being lipophilic cations, like 99mTc-MIBI, rhodamine dyes are known to accumulate in the myocardium and are substrates for Pgp, the protein implicated in MDR1 multidrug resistance. As the first step in determining whether 18F-labeled rhodamines might be useful as myocardial perfusion agents for PET, our objective was to develop synthetic methods for preparing the 18F-labeled compounds so that they could be evaluated in vivo. Rhodamine B was chosen as the prototype compound for development of the synthesis because the ethyl substituents on the amine moieties of rhodamine B protect them from side reactions, thus eliminating the need to include (and subsequently remove) protecting groups. The 2′-[18F]fluoroethyl ester of rhodamine B was synthesized by heating rhodamine B lactone with [18F]fluoroethyltosylate in acetonitrile at 165°C for 30 min.using [18F]fluoroethyl tosylate, which was prepared by the reaction of ethyleneglycol ditosylate with Kryptofix 2.2.2, K2CO3, and [18F]NaF in acetonitrile for 10 min. at 90°C. The product was purified by semi-preparative HPLC to produce the 2′-[18F]-fluoroethylester in >97% radiochemical purity with a specific activity of 1.3 GBq/μmol, an isolated decay corrected yield of 35%, and a total synthesis time of 90 min. PMID:19783150

  2. Potential Biochemical Mechanisms of Lung Injury in Diabetes

    PubMed Central

    Zheng, Hong; Wu, Jinzi; Jin, Zhen; Yan, Liang-Jun

    2017-01-01

    Accumulating evidence has shown that the lung is one of the target organs for microangiopathy in patients with either type 1 or type 2 diabetes mellitus (DM). Diabetes is associated with physiological and structural abnormalities in the diabetic lung concurrent with attenuated lung function. Despite intensive investigations in recent years, the pathogenic mechanisms of diabetic lung injury remain largely elusive. In this review, we summarize currently postulated mechanisms of diabetic lung injury. We mainly focus on the pathogenesis of diabetic lung injury that implicates key pathways, including oxidative stress, non-enzymatic protein glycosylation, polyol pathway, NF-κB pathway, and protein kinase c pathway. We also highlight that while numerous studies have mainly focused on tissue or cell damage in the lung, studies focusing on mitochondrial dysfunction in the diabetic lung have remained sketchy. Hence, further understanding of mitochondrial mechanisms of diabetic lung injury should provide invaluable insights into future therapeutic approaches for diabetic lung injury. PMID:28203478

  3. Potential Role of Lung Ventilation Scintigraphy in the Assessment of COPD

    PubMed Central

    Cukic, Vesna; Begic, Amela

    2014-01-01

    Objective: To highlight the importance of the lung ventilation scintigraphy (LVS) to study the regional distribution of lung ventilation and to describe most frequent abnormal patterns of lung ventilation distribution obtained by this technique in COPD and to compare the information obtained by LVS with the that obtained by traditional lung function tests. Material and methods: The research was done in 20 patients with previously diagnosed COPD who were treated in Intensive care unit of Clinic for pulmonary diseases and TB “Podhrastovi” Clinical Center, University of Sarajevo in exacerbation of COPD during first three months of 2014. Each patient was undergone to testing of pulmonary function by body plethysmography and ventilation/perfusion lung scintigraphy with radio pharmaceutics Technegas, 111 MBq Tc -99m-MAA. We compared the results obtained by these two methods. Results: All patients with COPD have a damaged lung function tests examined by body plethysmography implying airflow obstruction, but LVS indicates not only airflow obstruction and reduced ventilation, but also indicates the disorders in distribution in lung ventilation. Conclusion: LVS may add further information to the functional evaluation of COPD to that provided by traditional lung function tests and may contribute to characterizing the different phenotypes of COPD. PMID:25132709

  4. Dynamic contrast-enhanced perfusion area detector CT for non-small cell lung cancer patients: Influence of mathematical models on early prediction capabilities for treatment response and recurrence after chemoradiotherapy.

    PubMed

    Ohno, Yoshiharu; Koyama, Hisanobu; Fujisawa, Yasuko; Yoshikawa, Takeshi; Seki, Shinichiro; Sugihara, Naoki; Sugimura, Kazuro

    2016-01-01

    To determine the capability and influence of the mathematical method on dynamic contrast-enhanced (CE-) perfusion area detector CT (ADCT) for early prediction of treatment response as well as progression free and overall survival (PFS and OS) of non-small cell lung cancer (NSCLC) patients treated with chemoradiotherapy. Sixty-six consecutive stage III NSCLC patients underwent dynamic CE-perfusion ADCT examinations, chemoradiotherapy and follow-up examinations. Response Evaluation Criteria in Solid Tumors (RECIST) criteria were used to divide all patients into responders and non-responders. Differences in each of the indices for all targeted lesions between measurements obtained 2 weeks prior to the first and the third course of chemotherapy were determined for all patients. ROC analyses were employed to determine the capability of perfusion indices as markers for distinguishing RECIST responders from non-responders. To evaluate their capability for early prediction of therapeutic effect, OS of perfusion index-based responders and non-responders were compared by using the Kaplan-Meier method followed by log-rank test. Area under the curve (Az) for total perfusion by means of the dual-input maximum slope method was significantly larger than that of pulmonary arterial perfusion using the same method (p=0.007) and of perfusion with the single-input maximum slope method (p=0.007). Mean OS demonstrated significantly difference between responder- and non-responder groups for total perfusion (p=0.02). Mathematical models have significant influence on assessment for early prediction of treatment response, disease progression and overall survival using dynamic CE-perfusion ADCT for NSCLC patients treated with chemoradiotherapy. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  5. Potential of the isolated lung technique for the examination of sildenafil absorption from lung-delivered poly(lactide-co-glycolide) microparticles.

    PubMed

    Beck-Broichsitter, Moritz; Stoisiek, Katharina; Bohr, Adam; Aragão-Santiago, Leticia; Gessler, Tobias; Seeger, Werner; Kissel, Thomas

    2016-03-28

    Herein, we challenged the isolated lung (IL) technique to discriminate the performance of lung-delivered polymeric microparticles (MPs) having distinct drug release rates. For this purpose, sildenafil-loaded poly(lactide-co-glycolide) MPs were administered to the airspace of an IL model and the drug absorption profile was monitored. MPs (particle size of ~5μm) composed of PLGA of lower molecular weight (and glass transition temperature) manifested in the most rapid in vitro drug release (half-times ranging from <15 to ~200min). Moreover, microencapsulation resulted in a delayed sildenafil transfer over the air/perfusate barrier (half-times ranging from <5 to ~230min), where the actual ex vivo absorption profile depended on the release behavior of the utilized formulation. Finally, the obtained in vitro and ex vivo results were tested for level C, B and A correlations. The plotted data showed good agreement (R(2)>0.96) and the slopes of the resulting lines of regression (i.e., 0.80-0.85) indicated a slightly elevated in vitro drug release behavior. Overall, the IL model was able to differentiate between distinct microparticulate formulations and is, therefore, a valuable technique for early testing of potential inhalable controlled release medications. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Acute tumor vascular effects following fractionated radiotherapy in human lung cancer: In vivo whole tumor assessment using volumetric perfusion computed tomography

    SciTech Connect

    Ng, Q.-S.; Goh, Vicky; Milner, Jessica; Padhani, Anwar R.; Saunders, Michele I.; Hoskin, Peter J. . E-mail: peterhoskin@nhs.net

    2007-02-01

    Purpose: To quantitatively assess the in vivo acute vascular effects of fractionated radiotherapy for human non-small-cell lung cancer using volumetric perfusion computed tomography (CT). Methods and Materials: Sixteen patients with advanced non-small-cell lung cancer, undergoing palliative radiotherapy delivering 27 Gy in 6 fractions over 3 weeks, were scanned before treatment, and after the second (9 Gy), fourth (18 Gy), and sixth (27 Gy) radiation fraction. Using 16-detector CT, multiple sequential volumetric acquisitions were acquired after intravenous contrast agent injection. Measurements of vascular blood volume and permeability for the whole tumor volume were obtained. Vascular changes at the tumor periphery and center were also measured. Results: At baseline, lung tumor vascularity was spatially heterogeneous with the tumor rim showing a higher vascular blood volume and permeability than the center. After the second, fourth, and sixth fractions of radiotherapy, vascular blood volume increased by 31.6% (paired t test, p = 0.10), 49.3% (p = 0.034), and 44.6% (p = 0.0012) respectively at the tumor rim, and 16.4% (p = 0.29), 19.9% (p = 0.029), and 4.0% (p = 0.0050) respectively at the center of the tumor. After the second, fourth, and sixth fractions of radiotherapy, vessel permeability increased by 18.4% (p = 0.022), 44.8% (p = 0.0048), and 20.5% (p = 0.25) at the tumor rim. The increase in permeability at the tumor center was not significant after radiotherapy. Conclusion: Fractionated radiotherapy increases tumor vascular blood volume and permeability in human non-small-cell lung cancer. We have established the spatial distribution of vascular changes after radiotherapy; greater vascular changes were demonstrated at the tumor rim compared with the center.

  7. Ventilation/perfusion lung scintigraphy: what is still needed? A review considering technetium-99m-labeled macro-aggregates of albumin.

    PubMed

    Zöphel, Klaus; Bacher-Stier, Claudia; Pinkert, Jörg; Kropp, Joachim

    2009-01-01

    Lung perfusion scintigraphy (LPS) with technetium-99m-labeled macro-aggregates of albumin (Tc-99m-MAA) is well established in the diagnostic of pulmonary embolism (PE). In the last decade, it was shown that single-photon emission computer tomography (SPECT) acquisition of LPS overcame static scintigraphy. Furthermore, there are rare indications for LPS, such as preoperative quantification of regional lung function prior to lung resection or transplantation, optimization of lung cancer radiation therapy, quantification of right-left shunt, planning of intra-arterial chemotherapy, and several rare indications in pediatrics. Moreover, LPS with Tc-99m-MAA is a safe method with low radiation exposure. PE can also be diagnosed by spiral computer tomography (CT), ultrasound, magnetic resonance angiography, or pulmonary angiography (PA, former gold standard). The present review considers all these methods, especially spiral CT, and compares them with LPS with respect to sensitivity and specificity and gives an overview of established and newer publications. It shows that LPS with Tc-99m-MAA represents a diagnostic method of continuing value for PE. In comparison with spiral CT and/or PA, LPS is not to be defeated as mentioned also by the most actual Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) II reports. This applies in particular to chronic or recurring embolisms, whereas currently spiral CT may be of greater value for major or life-threatening embolisms. At present, LPS cannot be replaced by other methods in some applications, such as pediatrics or in the quantification of regional pulmonary function in a preoperative context or prior to radiation therapy. LPS still has a place in the diagnostics of PE and is irreplaceable in several rare indications as described earlier.

  8. A novel nanobody specific for respiratory surfactant protein A has potential for lung targeting

    PubMed Central

    Wang, Shan-Mei; He, Xian; Li, Nan; Yu, Feng; Hu, Yang; Wang, Liu-Sheng; Zhang, Peng; Du, Yu-Kui; Du, Shan-Shan; Yin, Zhao-Fang; Wei, Ya-Ru; Mulet, Xavier; Coia, Greg; Weng, Dong; He, Jian-Hua; Wu, Min; Li, Hui-Ping

    2015-01-01

    Lung-targeting drugs are thought to be potential therapies of refractory lung diseases by maximizing local drug concentrations in the lung to avoid systemic circulation. However, a major limitation in developing lung-targeted drugs is the acquirement of lung-specific ligands. Pulmonary surfactant protein A (SPA) is predominantly synthesized by type II alveolar epithelial cells, and may serve as a potential lung-targeting ligand. Here, we generated recombinant rat pulmonary SPA (rSPA) as an antigen and immunized an alpaca to produce two nanobodies (the smallest naturally occurring antibodies) specific for rSPA, designated Nb6 and Nb17. To assess these nanobodies’ potential for lung targeting, we evaluated their specificity to lung tissue and toxicity in mice. Using immunohistochemistry, we demonstrated that these anti-rSPA nanobodies selectively bound to rat lungs with high affinity. Furthermore, we intravenously injected fluorescein isothiocyanate-Nb17 in nude mice and observed its preferential accumulation in the lung to other tissues, suggesting high affinity of the nanobody for the lung. Studying acute and chronic toxicity of Nb17 revealed its safety in rats without causing apparent histological alterations. Collectively, we have generated and characterized lung-specific nanobodies, which may be applicable for lung drug delivery. PMID:25926731

  9. Potential mechanisms involved in the absorptive transport of cadmium in isolated perfused rabbit renal proximal tubules.

    PubMed

    Wang, Yanhua; Zalups, Rudolfs K; Barfuss, Delon W

    2010-03-01

    Lumen-to-cell transport, cellular accumulation, and toxicity of cadmium as ionic cadmium (Cd(2+)) or as the L-cysteine (Cys) or D,L-homocysteine (Hcy) S-conjugate of cadmium (Cys-S-Cd-S-Cys, Hcy-S-Cd-S-Hcy) were studied in isolated, perfused rabbit proximal tubular segments. When Cd(2+) (0.73 microM) or Cys-S-Cd-S-Cys (0.73 microM) was perfused through the lumen of S(2) segments of the proximal tubule, no visual evidence of cellular pathological changes was detected during 30 min of study. Cd(2+)-transport was temperature-dependent and was inhibited by Fe(2+), Zn(2+), and elevated concentrations of Ca(2+). Luminal uptake of Cys-S-Cd-S-Cys was also temperature-dependent and was inhibited by the amino acids L-cystine and L-arginine, while stimulated by L-methionine. Neither L-aspartate, L-glutamate, the synthetic dipeptide, Gly-Sar nor Zn(2+) had any effect on the rate of Cys-S-Cd-S-Cys transport. When delivered to the luminal compartment, Cd(2+) appears to be capable of utilizing certain transporter(s) of Zn(2+) and some transport systems sensitive to Ca(2+) and Fe(2+). In addition, Cys-S-Cd-S-Cys and Hcy-S-Cd-S-Hcy appear to be transportable substrates of one or more amino acid transporters participating in luminal absorption of the amino acid L-cystine (such as system b(0,+)). These findings indicate that multiple mechanisms could be involved in the luminal absorption of cadmium (Cd) in proximal tubular segments depending on its form. These findings provide a focus for future studies of Cd absorption in the proximal tubule. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

  10. POTENTIAL MECHANISMS INVOLVED IN THE ABSORPTIVE TRANSPORT OF CADMIUM IN ISOLATED PERFUSED RABBIT RENAL PROXIMAL TUBULES

    PubMed Central

    Wang, Yanhua; Zalups, Rudolfs K.; Barfuss, Delon W.

    2009-01-01

    Lumen-to-cell transport, cellular accumulation, and toxicity of cadmium as ionic cadmium (Cd2+) or as the L-cysteine (Cys) or D,L-homocysteine (Hcy) S-conjugate of cadmium (Cys-S-Cd-S-Cys, Hcy-S-Cd-S-Hcy) were studied in isolated, perfused rabbit proximal tubular segments. When Cd2+ (0.73μM) or Cys-S-Cd-S-Cys (0.73μM) was perfused through the lumen of S2 segments of the proximal tubule, no visual evidence of cellular pathological changes was detected during 30 min of study. Cd2+-transport was temperature-dependent and was inhibited by Fe2+, Zn2+, and elevated concentrations of Ca2+. Luminal uptake of Cys-S-Cd-S-Cys was also temperature-dependent and was inhibited by the amino acids L-cystine and L-arginine, while stimulated by L-methionine. Neither L-aspartate, L-glutamate, the synthetic dipeptide, Gly-Sar nor Zn2+ had any effect on the rate of Cys-S-Cd-S-Cys transport. Conclusions: When delivered to the luminal compartment, Cd2+ appears to be capable of utilizing certain transporter(s) of Zn2+ and some transport systems sensitive to Ca2+ and Fe2+. In addition, Cys-S-Cd-S-Cys and Hcy-S-Cd-S-Hcy appear to be transportable substrates of one or more amino acid transporters participating in luminal absorption of the amino acid L-cystine (such as system b0,+). These findings indicate that multiple mechanisms could be involved in the luminal absorption of cadmium (Cd) in proximal tubular segments depending on its form. These findings provide a focus for future studies of Cd absorption in the proximal tubule. PMID:20018233

  11. Are minimized perfusion circuits the better heart lung machines? Final results of a prospective randomized multicentre study.

    PubMed

    El-Essawi, A; Hajek, T; Skorpil, J; Böning, A; Sabol, F; Ostrovsky, Y; Hausmann, H; Harringer, W

    2011-11-01

    Minimized perfusion circuits (MPCs), although aiming at minimizing the adverse effects of cardiopulmonary bypass, have not yet gained popularity. This can be attributed to concerns regarding their safety, as well as lack of sufficient evidence of their benefit. Described is a randomized, multicentre study comparing the MPC - ROCsafeRX to standard cardiopulmonary bypass in patients undergoing elective coronary artery bypass grafting and/ or aortic valve replacement. Five hundred patients were included in the study (252 randomized to the ROCsafeRX group and 248 to standard cardiopulmonary bypass). Both groups were well matched for demographic characteristics and type of surgery. No operative mortality and no device-related complications were encountered. Transfusion requirement (333 ± 603 vs. 587 ± 1010 ml; p=0.001), incidence of atrial fibrillation (16.3% vs. 24.2%; p=0.03) and the incidence of major adverse events (9.1% vs. 16.5%; p=0.02) were all in favour of the MPC group. These results confirm both the safety and efficacy of the ROCsafeRX MPC for a large variety of cardiac patients. Minimized perfusion circuits should, therefore, play a greater role in daily practice so that as many patients as possible can benefit from their advantages.

  12. Potential therapeutic applications of hyaluronan in the lung

    PubMed Central

    Cantor, Jerome O

    2007-01-01

    Hyaluronan (HA), a long-chain polysaccharide, is currently being evaluated as a potential therapeutic agent for a number of inflammatory disorders. The effect of HA on inflammation appears to be related to its molecular size, with larger polysaccharide chains having anti-inflammatory activity and smaller ones having proinflammatory properties. This dichotomous behavior is particularly relevant to the work of our laboratory on an aerosolized preparation of HA to treat pulmonary emphysema. The breakdown of inhaled HA into smaller fragments could possibly induce an inflammatory reaction in the lung that counteracts any beneficial effect. Consequently, the proposed therapeutic use of HA will require development of treatment strategies aimed at minimizing its proinflammatory activity. PMID:18229566

  13. Dual-energy snap-shot perfusion CT in suspect pulmonary nodules and masses and for lung cancer staging.

    PubMed

    Sudarski, Sonja; Hagelstein, Claudia; Weis, Meike; Schoenberg, Stefan O; Apfaltrer, Paul

    2015-12-01

    Dual energy computed tomography (DECT) has proven its clinical usefulness for improved tissue characterization within the past years. In thoracic oncology, DECT can be used to differentiate between benign and malignant pulmonary nodules and masses. In patients with known lung cancer, DECT can add incremental functional information to staging scans, therapeutic response evaluation, as well as to the assessment of lung function. This review aims to give an overview on the current clinical utilities of DECT of the chest, its multiple post-processing applications and dose saving options. Furthermore, this review highlights promising applications of DECT that merit implementation in future clinical routine.

  14. WE-G-18C-02: Estimation of Optimal B-Value Set for Obtaining Apparent Diffusion Coefficient Free From Perfusion in Non-Small Cell Lung Cancer

    SciTech Connect

    Karki, K; Hugo, G; Ford, J; Saraiya, S; Weiss, E; Olsen, K; Groves, R

    2014-06-15

    Purpose: Diffusion-weighted MRI (DW-MRI) is increasingly being investigated for radiotherapy planning and response assessment. Selection of a limited number of b-values in DW-MRI is important to keep geometrical variations low and imaging time short. We investigated various b-value sets to determine an optimal set for obtaining monoexponential apparent diffusion coefficient (ADC) close to perfusion-insensitive intravoxel incoherent motion (IVIM) model ADC (ADCIVIM) in nonsmall cell lung cancer. Methods: Seven patients had 27 DW-MRI scans before and during radiotherapy in a 1.5T scanner. Respiratory triggering was applied to the echo-planar DW-MRI with TR=4500ms approximately, TE=74ms, pixel size=1.98X1.98mm{sub 2}, slice thickness=4–6mm and 7 axial slices. Diffusion gradients were applied to all three axes producing traceweighted images with eight b-values of 0–1000μs/μm{sup 2}. Monoexponential model ADC values using various b-value sets were compared to ADCIVIM using all b-values. To compare the relative noise in ADC maps, intra-scan coefficient of variation (CV) of active tumor volumes was computed. Results: ADCIVIM, perfusion coefficient and perfusion fraction for tumor volumes were in the range of 880-1622 μm{sup 2}/s, 8119-33834 μm{sup 2}/s and 0.104–0.349, respectively. ADC values using sets of 250, 800 and 1000; 250, 650 and 1000; and 250–1000μs/μm{sup 2} only were not significantly different from ADCIVIM(p>0.05, paired t-test). Error in ADC values for 0–1000, 50–1000, 100–1000, 250–1000, 500–1000, and three b-value sets- 250, 500 and 1000; 250, 650 and 1000; and 250, 800 and 1000μs/μm{sup 2} were 15.0, 9.4, 5.6, 1.4, 11.7, 3.7, 2.0 and 0.2% relative to the reference-standard ADCIVIM, respectively. Mean intrascan CV was 20.2, 20.9, 21.9, 24.9, 32.6, 25.8, 25.4 and 24.8%, respectively, whereas that for ADCIVIM was 23.3%. Conclusion: ADC values of two 3 b-value sets

  15. Adaptive 4D volume perfusion CT of lung cancer: effects of computerized motion correction and the range of volume coverage on measurement reproducibility.

    PubMed

    Lee, Sang Min; Lee, Hyun-Ju; Kim, Jung Im; Kang, Mi-Jin; Goo, Jin Mo; Park, Chang Min; Im, Jung-Gi

    2013-06-01

    The purpose of this study was to determine whether measurement reproducibility can be improved using computerized motion correction and whole-tumor coverage in adaptive 4D perfusion CT of lung cancer. Perfusion CT covering the entire z-axis of a mass was performed of 40 patients with lung cancer. Each perfusion CT study was performed in 93.5 seconds and included 17 repeated dynamic CT scans obtained using the Adaptive 4D Spiral mode. Tumor blood flow (BF), blood volume (BV), and permeability were measured in four different manners: in the entire tumor (whole-tumor coverage) without the use of motion correction; in the entire tumor with motion correction; in a small volume of interest (VOI) of tumor without motion correction; and in a small VOI with motion correction. Intra- and interobserver reproducibility were assessed through Bland-Altman analyses. The 95% limits of intraobserver reproducibility for BF, BV, and permeability were as follows: -52.1% to 48.0%, -22.4% to 27.8%, and -33.2% to 38.5%, respectively, in the whole tumor without motion correction; -53.3% to 45.6%, -17.7% to 20.6%, and -31.5% to 37.0% in the whole tumor with motion correction; -107.8% to 97.4%, -98.3% to 93.7%, and -132.3% to 100.7% in a small VOI of tumor without motion correction; and -74.9% to 98.6%, -74.5% to 88.1%, and -109.8% to 114.1% in a small VOI with motion correction. The 95% limits of interobserver reproducibility for BF, BV, and permeability were as follows: -57.0% to 62.5%, -36.8% to 52.6%, and -47.7% to 66.0%, respectively, in the whole tumor without motion correction; -55.7% to 55.8%, -25.8% to 42.0%, and -35.3% to 46.7% in the whole tumor with motion correction; -146.6% to 165.1%, -117.1% to 137.7%, and -143.2% to 149.8% in a small VOI of tumor without motion correction; and -106.2% to 133.6%, -99.5% to 122.4%, and -108.6% to 170.0% in a small VOI of tumor with motion correction. Overall, the best reproducibility was obtained when measurements were obtained in the entire

  16. Potential use of Doppler perfusion index in detection of occult liver metastases from colorectal cancer

    PubMed Central

    Patrlj, Leonardo; Bušić, Željko; Kolovrat, Marijan; Rakić, Mislav; Kliček, Robert; Židak, Marcel; Stipančić, Igor

    2014-01-01

    Many clinical and preclinical studies demonstrated that measurements of liver hemodynamic [Doppler perfusion index (DPI)] may be used to accurately diagnose and predict liver metastases from primary colorectal cancer in a research setting. However, Doppler measurements have some serious limitations when applied to general population. Ultrasound is very operator-dependent, and requires skilled examiners. Also, many conditions may limit the use of Doppler ultrasound and ultrasound in general, such as the presence of air in digestive tract, cardiac arrhythmias, vascular anomalies, obesity and other conditions. Therefore, in spite of the results from clinical studies, its value may be limited in everyday practice. On the contrary, scientific research of the DPI in detection of liver metastases is of great importance, since current research speaks strongly for the presence of systemic vasoactive substance responsible for observed hemodynamic changes. Identification of such a systemic vasoactive substance may lead to the development of a simple and reproducible laboratory test that may reliably identify the presence of occult liver metastases and therefore increase the success of adjuvant chemotherapy through better selection of patients. Further research in this subject is therefore of great importance. PMID:25392837

  17. Potential of optical microangiography to monitor cerebral blood perfusion and vascular plasticity following traumatic brain injury in mice in vivo

    NASA Astrophysics Data System (ADS)

    Jia, Yali; Alkayed, Nabil; Wang, Ruikang K.

    2009-07-01

    Optical microanglography (OMAG) is a recently developed imaging modality capable of volumetric imaging of dynamic blood perfusion, down to capillary level resolution, with an imaging depth up to 2.00 mm beneath the tissue surface. We report the use of OMAG to monitor the cerebral blood flow (CBF) over the cortex of mouse brain upon traumatic brain injury (TBI), with the cranium left intact, for a period of two weeks on the same animal. We show the ability of OMAG to repeatedly image 3-D cerebral vasculatures during pre- and post-traumatic phases, and to visualize the changes of regulated CBF and the vascular plasticity after TBI. The results indicate the potential of OMAG to explore the mechanism involved in the rehabilitation of TBI.

  18. Modulatory potential of resveratrol during lung inflammatory disease.

    PubMed

    Vargas, José Eduardo; Souto, André Arigony; Pitrez, Paulo Márcio Condessa; Stein, Renato Tetelbom; Porto, Bárbara Nery

    2016-11-01

    Neutrophils are the first cells to achieve the sites of infection or inflammation in the lungs. The massive accumulation of these cells is associated with acute and chronic lung injury. Therefore, they have been implicated in the pathogenesis of many lung diseases through the release of reactive oxygen intermediates, proteolytic enzymes and Neutrophil Extracellular Traps (NETs). The excessive and continuous release of NETs, fibers composed by decondensed chromatin coated with neutrophil proteins, are associated to the impairment of lung function in different pathological settings. Flavonoids inhibit the respiratory burst of neutrophils in mammals. However, one of these flavonoids, resveratrol has a particular chemical property. It reduce Cu(II) to Cu(I) form with concomitant formation of reactive oxygen species, which can produce DNA breakage as reported in several in vitro models. We hypothesize that direct resveratrol administration in lungs can cleave DNA in NETs, improving lung function during acute airway infections or chronic inflammatory lung diseases. If the hypothesis is correct, the control of NET formation can be used to reduce the inflammatory environment in lung after neutrophil stimuli. Additionally, the production of proinflammatory cytokines by neutrophils could be also diminished by resveratrol administration. In this sense, this flavonoid provides a multifaceted opportunity for treatment of lung diseases with strong or chronic neutrophil activation. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Transepithelial potential differences and Na(+) flux in isolated perfused gills of the crab Chasmagnathus granulatus (Grapsidae) acclimated to hyper- and hypo-salinity.

    PubMed

    Luquet, C M; Postel, U; Halperin, J; Urcola, M R; Marques, R; Siebers, D

    2002-01-01

    We studied the transepithelial potential difference (TEPD) and (22)Na flux across isolated perfused gills (anterior pair 5 and posterior pairs 6-8) of the crab Chasmagnathus granulatus acclimated to either hypo- or hyper-osmotic conditions. The gills of crabs acclimated to low salinity, perfused and bathed with 10 per thousand saline solutions, produced the following TEPDs (hemolymph side with respect to bath side): 0.4+/-0.7, -10.2+/-1.6, -10.8+/-1.3 and -6.7+/-1.3 mV for gills 5, 6, 7 and 8, respectively. Gills 6, 7 and 8 did not differ significantly. Reducing the saline concentration of bath and perfusate from 30 per thousand to 20 per thousand or 10 per thousand increased significantly the TEPDs of these gills. TEPDs of gill 6 (representative of posterior gills) were reduced by 69+/-5 % and 60+/-5 % after perfusion with ouabain or BaCl(2) (5 mmol l(-1) each), respectively. The same gill showed a net ouabain-sensitive Na(+) influx of 1150+/-290 microequiv g(-1) h(-1). Gill 6 of crabs acclimated to high salinity produced TEPDs of -1.5+/-0.1 and -1.3+/-0.09 mV after perfusion with 30 per thousand or 40 per thousand salines, respectively. Perfusion with ouabain or BaCl(2) reduced TEPDs by 76+/-7 % and 86+/-4 %, respectively. A net ouabain-sensitive Na(+) efflux of 2282+/-337 microequiv g(-1) h(-1) was recorded in gill 6 perfused with 38 per thousand saline.

  20. Myocardial Drug Distribution Generated from Local Epicardial Application: Potential Impact of Cardiac Capillary Perfusion in a Swine Model Using Epinephrine

    PubMed Central

    Maslov, Mikhail Y.; Edelman, Elazer R.; Pezone, Matthew J.; Wei, Abraham E.; Wakim, Matthew G.; Murray, Michael R.; Tsukada, Hisashi; Gerogiannis, Iraklis S.; Groothuis, Adam; Lovich, Mark A.

    2014-01-01

    the elevated drug levels in the coronary sinus effluent. Indeed, plasma levels, hemodynamic responses, and myocardial deposition remote from the point of release were similar following local EC or IV delivery. Therefore, the coronary vasculature shapes the pharmacokinetics of local myocardial delivery of small catecholamine drugs in large animal models. Optimal design of epicardial drug delivery systems must consider the underlying bulk capillary perfusion currents within the tissue to deliver drug to tissue targets and may favor therapeutic molecules with better potential retention in myocardial tissue. PMID:25234821

  1. Harnessing the potential of lung stem cells for regenerative medicine.

    PubMed

    McQualter, Jonathan L; Anthony, Desiree; Bozinovski, Steven; Prêle, Cecilia M; Laurent, Geoffrey J

    2014-11-01

    In response to recurrent exposure to environmental insults such as allergens, pollution, irritants, smoke and viral/bacterial infection, the epithelium of the lung is continually damaged. Homeostasis of the lung requires a balance between immune regulation and promotion of tissue regeneration, which requires the co-ordinated proliferation and differentiation of stem and progenitor cells. In this review we reflect on the current understanding of lung epithelial stem and progenitor cells and advocate a model hierarchy in which self-renewing multipotent lung epithelial stem cells give rise to lineage restricted progenitor cells that repopulate airway and alveolar epithelial cell lineages during homeostasis and repair. We also discuss the role of mesenchymal progenitor cells in maintaining the structural integrity of the lung and propose a model in which mesenchymal cells act as the quintessential architects of lung regeneration by providing molecular signals, such as FGF-10, to regulate the fate and specificity of epithelial stem and progenitor cells. Moreover, we discuss the current status and future prospects for translating lung stem cell therapies to the clinic to replace, repair, or regenerate diseased lung tissue. This article is part of a directed issue entitled: Regenerative Medicine: the challenge of translation.

  2. ADAM28: a potential oncogene involved in asbestos-related lung adenocarcinomas.

    PubMed

    Wright, Casey M; Larsen, Jill E; Hayward, Nicholas K; Martins, Maria U; Tan, Maxine E; Davidson, Morgan R; Savarimuthu, Santiyagu M; McLachlan, Rebecca E; Passmore, Linda H; Windsor, Morgan N; Clarke, Belinda E; Duhig, Edwina E; Yang, Ian A; Bowman, Rayleen V; Fong, Kwun M

    2010-08-01

    Asbestos-related lung cancer accounts for 4-12% of all lung cancers worldwide. Since putative mechanisms of carcinogenesis differ between asbestos and tobacco induced lung cancers, tumors induced by the two agents may be genetically distinct. To identify gene expression biomarkers associated with asbestos-related lung tumorigenicity we performed gene expression array analysis on tumors of 36 patients with primary lung adenocarcinoma, comparing 12 patients with lung asbestos body counts above levels associated with urban dwelling (ARLC-AC: asbestos-related lung cancer-adenocarcinoma) with 24 patients with no asbestos bodies (NARLC-AC: non-asbestos related lung cancer-adenocarcinoma). Genes differentially expressed between ARLC-AC and NARLC-AC were identified on fold change and P value, and then prioritized using gene ontology. Candidates included ZNRF3, ADAM28, PPP1CA, IRF6, RAB3D, and PRDX1. Expression of these six genes was technically and biologically replicated by qRT-PCR in the training set and biologically validated in three independent test sets. ADAM28, encoding a disintegrin and metalloproteinase domain protein that interacts with integrins, was consistently upregulated in ARLC across all four datasets. Further studies are being designed to investigate the possible role of this gene in asbestos lung tumorigenicity, its potential utility as a marker of asbestos related lung cancer for purposes of causal attribution, and its potential as a treatment target for lung cancers arising in asbestos exposed persons.

  3. To Find a Better Dosimetric Parameter in the Predicting of Radiation-Induced Lung Toxicity Individually: Ventilation, Perfusion or CT based

    PubMed Central

    Xiao, Lin-Lin; Yang, Guoren; Chen, Jinhu; Wang, Xiaohui; Wu, Qingwei; Huo, Zongwei; Yu, Qingxi; Yu, Jinming; Yuan, Shuanghu

    2017-01-01

    This study aimed to find a better dosimetric parameter in predicting of radiation-induced lung toxicity (RILT) in patients with non-small cell lung cancer (NSCLC) individually: ventilation(V), perfusion (Q) or computerized tomography (CT) based. V/Q single-photon emission computerized tomography (SPECT) was performed within 1 week prior to radiotherapy (RT). All V/Q imaging data was integrated into RT planning system, generating functional parameters based on V/Q SPECT. Fifty-seven NSCLC patients were enrolled in this prospective study. Fifteen (26.3%) patients underwent grade ≥2 RILT, the remaining forty-two (73.7%) patients didn’t. Q-MLD, Q-V20, V-MLD, V-V20 of functional parameters correlated more significantly with the occurrence of RILT compared to V20, MLD of anatomical parameters (r = 0.630; r = 0.644; r = 0.617; r = 0.651 vs. r = 0.424; r = 0.520 p < 0.05, respectively). In patients with chronic obstructive pulmonary diseases (COPD), V functional parameters reflected significant advantage in predicting RILT; while in patients without COPD, Q functional parameters reflected significant advantage. Analogous results were existed in fractimal analysis of global pulmonary function test (PFT). In patients with central-type NSCLC, V parameters were better than Q parameters; while in patients with peripheral-type NSCLC, the results were inverse. Therefore, this study demonstrated that choosing a suitable dosimetric parameter individually can help us predict RILT accurately. PMID:28294159

  4. Research Resource: Diagnostic and Therapeutic Potential of Nuclear Receptor Expression in Lung Cancer

    PubMed Central

    Xie, Yang; Lee, Woochang; Bookout, Angie L.; Girard, Luc; Raso, Gabriela; Behrens, Carmen; Wistuba, Ignacio I.; Gadzar, Adi F.; Minna, John D.; Mangelsdorf, David J.

    2012-01-01

    Lung cancer is the leading cause of cancer-related death. Despite a number of studies that have provided prognostic biomarkers for lung cancer, a paucity of reliable markers and therapeutic targets exist to diagnose and treat this aggressive disease. In this study we investigated the potential of nuclear receptors (NRs), many of which are well-established drug targets, as therapeutic markers in lung cancer. Using quantitative real-time PCR, we analyzed the expression of the 48 members of the NR superfamily in a human panel of 55 normal and lung cancer cell lines. Unsupervised cluster analysis of the NR expression profile segregated normal from tumor cell lines and grouped lung cancers according to type (i.e. small vs. non-small cell lung cancers). Moreover, we found that the NR signature was 79% accurate in diagnosing lung cancer incidence in smokers (n = 129). Finally, the evaluation of a subset of NRs (androgen receptor, estrogen receptor, vitamin D receptor, and peroxisome proliferator-activated receptor-γ) demonstrated the therapeutic potential of using NR expression to predict ligand-dependent growth responses in individual lung cancer cells. Preclinical evaluation of one of these receptors (peroxisome proliferator activated receptor-γ) in mouse xenografts confirmed that ligand-dependent inhibitory growth responses in lung cancer can be predicted based on a tumor's receptor expression status. Taken together, this study establishes NRs as theragnostic markers for predicting lung cancer incidence and further strengthens their potential as therapeutic targets for individualized treatment. PMID:22700587

  5. Genetically manipulated mouse models of lung disease: potential and pitfalls

    PubMed Central

    Choi, Alexander J. S.; Owen, Caroline A.; Choi, Augustine M. K.

    2012-01-01

    Gene targeting in mice (transgenic and knockout) has provided investigators with an unparalleled armamentarium in recent decades to dissect the cellular and molecular basis of critical pathophysiological states. Fruitful information has been derived from studies using these genetically engineered mice with significant impact on our understanding, not only of specific biological processes spanning cell proliferation to cell death, but also of critical molecular events involved in the pathogenesis of human disease. This review will focus on the use of gene-targeted mice to study various models of lung disease including airways diseases such as asthma and chronic obstructive pulmonary disease, and parenchymal lung diseases including idiopathic pulmonary fibrosis, pulmonary hypertension, pneumonia, and acute lung injury. We will attempt to review the current technological approaches of generating gene-targeted mice and the enormous dataset derived from these studies, providing a template for lung investigators. PMID:22198907

  6. Potentiation of chemically induced lung fibrosis by thorax irradiation. [Mice

    SciTech Connect

    Haschek, W.M.; Meyer, K.R.; Ullrich, R.L.; Witschi, H.P.

    1980-04-01

    Intraperitoneal injection of butylated hydroxytoluene (BHT) causes epithelial cell death, followed 2 to 4 days later by extensive proliferation of type II alveolar cells in mouse lung. Five to 8 days after BHT, most dividing cells are capillary endothelial cells or interstitial cells. In animials that were exposed to 200 rad thorax irradiation immediately or 1 day after BHT, lung hydroxyproline was increased 2 weeks later. The response was dose dependent, and the interaction between BHT and thorax irradiation was synergistic. Light microscopy showed abnormal accumulation of collagen in the alveolar septa. Lung hydroxyproline was not increased in animals that were irradiated 6 days after BHT, compared to animals treated with BHT alone. We concluded that fibrosis develops if lung is damaged by a blood-borne agent and radiation to the thorax occurs at a time when it may compromise alveolar reepithelialization. Exposure to x-rays during proliferation of capillary endothelial cells or interstitial cells does not enhance development of fibrosis.

  7. Successful lung transplant from donor after cardiac death: a potential solution to shortage of thoracic organs.

    PubMed

    McKellar, Stephen H; Durham, Lucian A; Scott, John P; Cassivi, Stephen D

    2010-02-01

    Lung transplant is an effective treatment for patients with end-stage lung disease but is limited because of the shortage of acceptable donor organs. Organ donation after cardiac death is one possible solution to the organ shortage because it could expand the pool of potential donors beyond brain-dead and living donors. We report the preliminary experience of Mayo Clinic with donation after cardiac death, lung procurement, and transplant.

  8. Study of Stress Induced Failure of the Blood-gas Barrier and the Epithelial-epithelial Cells Connections of the Lung of the Domestic Fowl, Gallus gallus Variant Domesticus after Vascular Perfusion

    PubMed Central

    Maina, John N; Jimoh, Sikiru A

    2013-01-01

    Complete blood-gas barrier breaks (BGBBs) and epithelial-epithelial cells connections breaks (E-ECCBs) were enumerated in the lungs of free range chickens, Gallus gallus variant domesticus after vascular perfusion at different pressures. The E-ECCBs surpassed the BGBBs by a factor of ~2. This showed that the former parts of the gas exchange tissue were structurally weaker or more vulnerable to failure than the latter. The differences in the numbers of BGBBs and E-ECCBs in the different regions of the lung supplied with blood by the 4 main branches of the pulmonary artery (PA) corresponded with the diameters of the blood vessels, the angles at which they bifurcated from the PA, and the positions along the PA where they branched off. Most of the BGBBs and the E-ECCBs occurred in the regions supplied by the accessory- and the caudomedial branches: the former is the narrowest branch and the first blood vessel to separate from the PA while the latter is the most direct extension of the PA and is the widest. The E-ECCBs appeared to separate and fail from tensing of the blood capillary walls, as the perfusion- and intramural pressures increased. Compared to the mammalian lungs on which data are available, i.e., those of the rabbit, the dog, and the horse, the blood-gas barrier of the lung of free range chickens appears to be substantially stronger for its thinness. PMID:25288905

  9. The Differential Absorption of a Series of P-Glycoprotein Substrates in Isolated Perfused Lungs from Mdr1a/1b Genetic Knockout Mice can be Attributed to Distinct Physico-Chemical Properties: an Insight into Predicting Transporter-Mediated, Pulmonary Specific Disposition.

    PubMed

    Price, Daniel F; Luscombe, Chris N; Eddershaw, Peter J; Edwards, Chris D; Gumbleton, Mark

    2017-07-12

    To examine if pulmonary P-glycoprotein (P-gp) is functional in an intact lung; impeding the pulmonary absorption and increasing lung retention of P-gp substrates administered into the airways. Using calculated physico-chemical properties alone build a predictive Quantitative Structure-Activity Relationship (QSAR) model distinguishing whether a substrate's pulmonary absorption would be limited by P-gp or not. A panel of 18 P-gp substrates were administered into the airways of an isolated perfused mouse lung (IPML) model derived from Mdr1a/Mdr1b knockout mice. Parallel intestinal absorption studies were performed. Substrate physico-chemical profiling was undertaken. Using multivariate analysis a QSAR model was established. A subset of P-gp substrates (10/18) displayed pulmonary kinetics influenced by lung P-gp. These substrates possessed distinct physico-chemical properties to those P-gp substrates unaffected by P-gp (8/18). Differential outcomes were not related to different intrinsic P-gp transporter kinetics. In the lung, in contrast to intestine, a higher degree of non-polar character is required of a P-gp substrate before the net effects of efflux become evident. The QSAR predictive model was applied to 129 substrates including eight marketed inhaled drugs, all these inhaled drugs were predicted to display P-gp dependent pulmonary disposition. Lung P-gp can affect the pulmonary kinetics of a subset of P-gp substrates. Physico-chemical relationships determining the significance of P-gp to absorption in the lung are different to those operative in the intestine. Our QSAR framework may assist profiling of inhaled drug discovery candidates that are also P-gp substrates. The potential for P-gp mediated pulmonary disposition exists in the clinic.

  10. Technetium-99m bis (aminoethanethiol) complexes with amine sidechains--potential brain perfusion imaging agents for SPECT

    SciTech Connect

    Efange, S.M.; Kung, H.F.; Billings, J.; Guo, Y.Z.; Blau, M.

    1987-06-01

    In an effort to develop new clinically useful technetium-99m bis(aminoethanethiol) ((/sup 99m/Tc)BAT) complexes for the evaluation of regional cerebral perfusion, two new BAT ligands containing amines in the sidechain were synthesized and subsequently complexed with /sup 99m/Tc to yield the target complexes: (/sup 99m/Tc)DEA and (/sup 99m/Tc)TMPDA. Each complex was obtained as mixtures of two isomers, syn and anti, which were separated chromatographically. In biodistribution studies, both isomers of (/sup 99m/Tc)TMPDA showed little uptake in the brain. In contrast, the brain uptake values at 2 and 15 min for (/sup 99m/Tc)DEA-anti were 0.99 and 0.26, whereas, the corresponding values for DEA-syn were 2.27, 0.64% dose/organ, respectively. Autoradiographic studies (in rats) using both isomers of (/sup 99m/Tc)DEA show a fixed regional distribution and a higher concentration of radioactivity in the gray matter relative to the white matter. Planar imaging using (/sup 99m/Tc)DEA-syn clearly demonstrates localization of the complex in the brain with a T 1/2 of 41 min, suggesting some potential for use with single photon emission computed tomography.

  11. Comparison of BOLD cerebrovascular reactivity mapping and DSC MR perfusion imaging for prediction of neurovascular uncoupling potential in brain tumors.

    PubMed

    Pillai, Jay J; Zacà, Domenico

    2012-08-01

    The coupling mechanism between neuronal firing and cerebrovascular dilatation can be significantly compromised in cerebral diseases, making it difficult to identify eloquent cortical areas near or within resectable lesions by using Blood Oxygen Level Dependent (BOLD) fMRI. Several metabolic and vascular factors have been considered to account for this lesion-induced neurovascular uncoupling (NVU), but no imaging gold standard exists currently for the detection of NVU. However, it is critical in clinical fMRI studies to evaluate the risk of NVU because the presence of NVU may result in false negative activation that may result in inadvertent resection of eloquent cortex, resulting in permanent postoperative neurologic deficits. Although NVU results from a disruption of one or more components of a complex cellular and chemical neurovascular coupling cascade (NCC) MR imaging is only able to evaluate the final step in this NCC involving the ultimate cerebrovascular response. Since anything that impairs cerebrovascular reactivity (CVR) will necessarily result in NVU, regardless of its effect more proximally along the NCC, we can consider mapping of CVR as a surrogate marker of NVU potential. We hypothesized that BOLD breath-hold (BH) CVR mapping can serve as a better marker of NVU potential than T2* Dynamic Susceptibility Contrast gadolinium perfusion MR imaging, because the latter is known to only reflect NVU risk associated with high grade gliomas by determining elevated relative cerebral blood volume (rCBV) and relative cerebral blood flow (rCBF) related to tumor angiogenesis. However, since low and intermediate grade gliomas are not associated with such tumoral hyperperfusion, BOLD BH CVR mapping may be able to detect such NVU potential even in lower grade gliomas without angiogenesis, which is the hallmark of glioblastomas. However, it is also known that glioblastomas are associated with variable NVU, since angiogenesis may not always result in NVU. Perfusion

  12. Perfusion- and pattern-based quantitative CT indexes using contrast-enhanced dual-energy computed tomography in diffuse interstitial lung disease: relationships with physiologic impairment and prediction of prognosis.

    PubMed

    Moon, Jung Won; Bae, Jang Pyo; Lee, Ho Yun; Kim, Namkug; Chung, Man Pyo; Park, Hye Yun; Chang, Yongjun; Seo, Joon Beom; Lee, Kyung Soo

    2016-05-01

    To evaluate automated texture-based segmentation of dual-energy CT (DECT) images in diffuse interstitial lung disease (DILD) patients and prognostic stratification by overlapping morphologic and perfusion information of total lung. Suspected DILD patients scheduled for surgical biopsy were prospectively included. Texture patterns included ground-glass opacity (GGO), reticulation and consolidation. Pattern- and perfusion-based CT measurements were assessed to extract quantitative parameters. Accuracy of texture-based segmentation was analysed. Correlations between CT measurements and pulmonary function test or 6-minute walk test (6MWT) were calculated. Parameters of idiopathic pulmonary fibrosis/usual interstitial pneumonia (IPF/UIP) and non-IPF/UIP were compared. Survival analysis was performed. Overall accuracy was 90.47% for whole lung segmentation. Correlations between mean iodine values of total lung, 50-97.5th (%) attenuation and forced vital capacity or 6MWT were significant. Volume of GGO, reticulation and consolidation had significant correlation with DLco or SpO2 on 6MWT. Significant differences were noted between IPF/UIP and non-IPF/UIP in 6MWT distance, mean iodine value of total lung, 25-75th (%) attenuation and entropy. IPF/UIP diagnosis, GGO ratio, DILD extent, 25-75th (%) attenuation and SpO2 on 6MWT showed significant correlations with survival. DECT combined with pattern analysis is useful for analysing DILD and predicting survival by provision of morphology and enhancement. • Dual-energy CT (DECT) produces morphologic and parenchymal enhancement information. • Automated lung segmentation enables analysis of disease extent and severity. • This prospective study showed value of DECT in DILD patients. • Parameters on DECT enable characterization and survival prediction of DILD.

  13. Arterial Spin Labeling Magnetic Resonance Perfusion for Traumatic Brain Injury: Technical Challenges and Potentials.

    PubMed

    Andre, Jalal B

    2015-10-01

    Traumatic brain injury (TBI), including concussion, is a public health concern, as it affects over 1.7 million persons in the United States per year. Yet, the diagnosis of TBI, particularly mild TBI (mTBI), can be controversial, as neuroimaging findings can be sparse on conventional magnetic resonance and computed tomography examinations, and when present, often poorly correlate with clinical signs and symptoms. Furthermore, the discussion of TBI, concussion, and head impact exposure is immediately complicated by the many differing opinions of what constitutes each, their respective severities, and how the underlying biomechanics of the inciting head impact might alter the distribution, severity, and prognosis of the underlying brain injury. Advanced imaging methodologies hold promise in improving the sensitivity and detectability of associated imaging biomarkers that might better correlate with patient outcome and prognostication, allowing for improved triage and therapeutic guidance in the setting of TBI, particularly in mTBI. This work will examine the defining symptom complex associated with mTBI and explore changes in cerebral blood flow measured by arterial spin labeling, as a potential imaging biomarker for TBI, and briefly correlate these observations with findings identified by single photon emission computed tomography and positron emission tomography imaging.

  14. An ex vivo comparison of adenosine and lidocaine solution and University of Wisconsin solution for hypothermic machine perfusion of porcine kidneys: potential for development.

    PubMed

    Hamaoui, Karim; Aftab, Adeel; Gowers, Sally; Boutelle, Martyn; Cook, Terry; Rudd, Donna; Dobson, Geoffrey P; Papalois, Vassilios

    2017-02-01

    The optimal hypothermic machine perfusion (HMP) solution has not yet been developed. An adenosine and lidocaine (AL) solution has been shown to be protective in cardiac preservation. The aim of the present study was to examine a modified AL solution with low Ca(2+), 16 mM Mg(2+), and 4% albumin on kidney preservation compared with University Wisconsin solution (UW). Twenty donation of organs after cardiac death porcine kidneys underwent HMP for 10 h (AL, n = 10; UW, n = 10) and then 2 h of normothermic reperfusion. Perfusion dynamics, functional parameters, histology, and real-time microdialysis were used to assess kidney responses and viability. During HMP, modified AL-perfused kidneys maintained higher flow rates (21.5 versus 17.9 mL/min/100 g, P = 0.01), with perfusion flow index during the first 3 h 25% greater than with UW (AL = 0.50 ± 0.2, UW = 0.40 ± 0.17 mL/min/100 g/mmHg; P = 0.03), followed by an increase in UW kidneys which was not significantly different to AL over the remaining 7 h (0.54 versus 0.55 mL/min/100 g/mmHg, respectively). During warm reperfusion, there were no significant differences between the two HMP groups in creatinine clearance, oxygen, and glucose consumption between groups. Modified AL kidneys had significantly lower perfusate lactates (3.1 versus 4.1 mmol/L, P = 0.04) during reperfusion and lower cortical lactate levels (AL = 0.66 ± 0.31, UW = 0.89 ± 0.53 mM, P = 0.33). Histology showed similar degrees of reperfusion injury. We conclude that HMP with modified AL solution showed improved perfusion compared with UW and lower perfusate lactate levels during warm reperfusion. Further modification of the AL composition is warranted and may lead to more rapid kidney stabilization and improved graft viability assessment, potentially expanding donor pools. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Dutch perfusion incident survey.

    PubMed

    Groenenberg, Ingrid; Weerwind, Patrick W; Everts, Peter A M; Maessen, Jos G

    2010-09-01

    Cardiopulmonary bypass procedures remain complex, involving many potential risks. Therefore, a nationwide retrospective study was conducted to gain insight into the number of incidents and accidents in Dutch adult perfusion practice. An anonymous postal survey (85 questions about hardware, disposables, fluids and medication, air emboli, anticoagulation, practice, and safety measures) was sent to all Dutch perfusionists involved in adult cardiovascular perfusion during 2006 and 2007. To guarantee complete anonymity, respondents were asked to return the survey to a notary who discarded personal information. The net response rate was 72% and covered 23,500 perfusions. Individual respondents performed 240 ± 103 perfusions during the 2-year study period and had 13.8 ± 8.7 years of practical experience. The incident rate was 1 per 15.6 perfusions and the adverse event rate was 1 per 1,236 perfusions. The three most reported incidents were: (1) persistent inability to raise the activated coagulation time above 400s during perfusion (184 incidents); (2) an allergic or anaphylactic reaction to drugs, fluids, or blood products (114 incidents); and (3) clotting formation in the extracorporeal circuit (74 incidents). Furthermore, pre-bypass safety measures showed no statistically significant association with the reported incidents. In comparison with data from the recent literature, the reported number of incidents is high. Nevertheless, the adverse outcome rate is well matched to other published surveys. The relatively high response rate conveys the impression that the Dutch perfusionist is vigilant and willing to report incidents. Hence, a web-based Dutch perfusion incident registration system is recommended.

  16. International Lung Cancer Consortium: Coordinated association study of 10 potential lung cancer susceptibility variants

    PubMed Central

    Truong, Therese; Sauter, Wiebke; McKay, James D.; Hosgood, H.Dean; Gallagher, Carla; Amos, Christopher I.; Spitz, Margaret; Muscat, Joshua; Lazarus, Philip; Illig, Thomas; Wichmann, H.Erich; Bickeböller, Heike; Risch, Angela; Dienemann, Hendrik; Zhang, Zuo-Feng; Naeim, Behnaz Pezeshki; Yang, Ping; Zienolddiny, Shanbeh; Haugen, Aage; Le Marchand, Loïc; Hong, Yun-Chul; Kim, Jin Hee; Duell, Eric J.; Andrew, Angeline S.; Kiyohara, Chikako; Shen, Hongbing; Matsuo, Keitaro; Suzuki, Takeshi; Seow, Adeline; Ng, Daniel P.K.; Lan, Qing; Zaridze, David; Szeszenia-Dabrowska, Neonilia; Lissowska, Jolanta; Rudnai, Peter; Fabianova, Eleonora; Constantinescu, Vali; Bencko, Vladimir; Foretova, Lenka; Janout, Vladimir; Caporaso, Neil E.; Albanes, Demetrius; Thun, Michael; Landi, Maria Teresa; Trubicka, Joanna; Lener, Marcin; Lubiński, Jan; Wang, Ying; Chabrier, Amélie; Boffetta, Paolo; Brennan, Paul; Hung, Rayjean J.

    2010-01-01

    Background. Analysis of candidate genes in individual studies has had only limited success in identifying particular gene variants that are conclusively associated with lung cancer risk. In the International Lung Cancer Consortium (ILCCO), we conducted a coordinated genotyping study of 10 common variants selected because of their prior evidence of an association with lung cancer. These variants belonged to candidate genes from different cancer-related pathways including inflammation (IL1B), folate metabolism (MTHFR), regulatory function (AKAP9 and CAMKK1), cell adhesion (SEZL6) and apoptosis (FAS, FASL, TP53, TP53BP1 and BAT3). Methods. Genotype data from 15 ILCCO case–control studies were available for a total of 8431 lung cancer cases and 11 072 controls of European descent and Asian ethnic groups. Unconditional logistic regression was used to model the association between each variant and lung cancer risk. Results. Only the association between a non-synonymous variant of TP53BP1 (rs560191) and lung cancer risk was significant (OR = 0.91, P = 0.002). This association was more striking for squamous cell carcinoma (OR = 0.86, P = 6 × 10−4). No heterogeneity by center, ethnicity, smoking status, age group or sex was observed. In order to confirm this association, we included results for this variant from a set of independent studies (9966 cases/11 722 controls) and we reported similar results. When combining all these studies together, we reported an overall OR = 0.93 (0.89–0.97) (P = 0.001). This association was significant only for squamous cell carcinoma [OR = 0.89 (0.85–0.95), P = 1 × 10−4]. Conclusion. This study suggests that rs560191 is associated to lung cancer risk and further highlights the value of consortia in replicating or refuting published genetic associations. PMID:20106900

  17. The Potential Role of Lung Microbiota in Lung Cancer Attributed to Household Coal Burning Exposures

    PubMed Central

    Hosgood, H. Dean; Sapkota, Amy R.; Rothman, Nathaniel; Rohan, Thomas; Hu, Wei; Xu, Jun; Vermeulen, Roel; He, Xingzhou; White, James Robert; Wu, Guoping; Wei, Fusheng; Mongodin, Emmanuel F.; Lan, Qing

    2014-01-01

    Bacteria influence site-specific disease etiology and the host’s ability to metabolize xenobiotics, such as polycyclic aromatic hydrocarbons (PAHs). Lung cancer in Xuanwei, China has been attributed to PAH-rich household air pollution from burning coal. This study seeks to explore the role of lung microbiota in lung cancer among never smoking Xuanwei women and how coal burning may influence these associations. DNA from sputum and buccal samples of never smoking lung cancer cases (n = 8, in duplicate) and controls (n = 8, in duplicate) in two Xuanwei villages was extracted using a multi-step enzymatic and physical lysis, followed by a standardized clean-up. V1–V2 regions of 16S rRNA genes were PCR-amplified. Purified amplicons were sequenced by 454 FLX Titanium pyrosequencing and high-quality sequences were evaluated for diversity and taxonomic membership. Bacterial diversity among cases and controls was similar in buccal samples (P = 0.46), but significantly different in sputum samples (P = 0.038). In sputum, Granulicatella (6.1 vs. 2.0%; P = 0.0016), Abiotrophia (1.5 vs. 0.085%; P = 0.0036), and Streptococcus (40.1 vs. 19.8%; P = 0.0142) were enriched in cases compared with controls. Sputum samples had on average 488.25 species-level OTUs in the flora of cases who used smoky coal (PAHrich) compared with 352.5 OTUs among cases who used smokeless coal (PAH-poor; P = 0.047). These differences were explained by the Bacilli species (Streptococcus infantis and Streptococcus anginosus). Our small study suggests that never smoking lung cancer cases have differing sputum microbiota than controls. PMID:24895247

  18. The potential role of lung microbiota in lung cancer attributed to household coal burning exposures.

    PubMed

    Hosgood, H Dean; Sapkota, Amy R; Rothman, Nathaniel; Rohan, Thomas; Hu, Wei; Xu, Jun; Vermeulen, Roel; He, Xingzhou; White, James Robert; Wu, Guoping; Wei, Fusheng; Mongodin, Emmanuel F; Lan, Qing

    2014-10-01

    Bacteria influence site-specific disease etiology and the host's ability to metabolize xenobiotics, such as polycyclic aromatic hydrocarbons (PAHs). Lung cancer in Xuanwei, China has been attributed to PAH-rich household air pollution from burning coal. This study seeks to explore the role of lung microbiota in lung cancer among never smoking Xuanwei women and how coal burning may influence these associations. DNA from sputum and buccal samples of never smoking lung cancer cases (n = 8, in duplicate) and controls (n = 8, in duplicate) in two Xuanwei villages was extracted using a multi-step enzymatic and physical lysis, followed by a standardized clean-up. V1-V2 regions of 16S rRNA genes were PCR-amplified. Purified amplicons were sequenced by 454 FLX Titanium pyrosequencing and high-quality sequences were evaluated for diversity and taxonomic membership. Bacterial diversity among cases and controls was similar in buccal samples (P = 0.46), but significantly different in sputum samples (P = 0.038). In sputum, Granulicatella (6.1 vs. 2.0%; P = 0.0016), Abiotrophia (1.5 vs. 0.085%; P = 0.0036), and Streptococcus (40.1 vs. 19.8%; P = 0.0142) were enriched in cases compared with controls. Sputum samples had on average 488.25 species-level OTUs in the flora of cases who used smoky coal (PAH-rich) compared with 352.5 OTUs among cases who used smokeless coal (PAH-poor; P = 0.047). These differences were explained by the Bacilli species (Streptococcus infantis and Streptococcus anginosus). Our small study suggests that never smoking lung cancer cases have differing sputum microbiota than controls. Further, bacteria found in sputum may be influenced by environmental exposures associated with the type of coal burned in the home.

  19. Pediatric Lung Transplantation.

    PubMed

    Sweet, Stuart C

    2017-06-01

    Pediatric lung transplant is a viable option for treatment of end-stage lung disease in children, with > 100 pediatric lung transplants reported to the Registry of the International Society of Heart and Lung Transplantation each year. Long-term success is limited by availability of donor organs, debilitation as a result of chronic disease, impaired mucus clearance resulting from both surgical and pharmacologic interventions, increased risk for infection resulting from immunosuppression, and most importantly late complications, such as chronic lung allograft dysfunction. Opportunities for investigation and innovation remain in all of these domains: (1) Ex vivo lung perfusion is a promising technology with the potential for increasing the lung donor pool, (2) evolving extracorporeal support strategies coupled with effective rehabilitation will effectively bridge critically ill patients to transplant, and most importantly, (3) research efforts intended to increase our understanding of the underlying mechanisms of chronic lung allograft dysfunction will ultimately lead to the development of effective therapies to prevent or treat the variety of chronic lung allograft dysfunction presentations. Copyright © 2017 by Daedalus Enterprises.

  20. Checkpoint inhibitors in lung cancer: latest developments and clinical potential

    PubMed Central

    Schvartsman, Gustavo; Ferrarotto, Renata; Massarelli, Erminia

    2016-01-01

    Lung cancer is the leading cause of cancer death in the United States. The vast majority of patients are diagnosed with metastatic disease with a 5-year survival rate of less than 5%. After first-line chemotherapy or biomarker-matched targeted therapy, only suitable for a small group of patients, further systemic therapy options rendered very limited, if any, benefit until recently. Checkpoint inhibitors have significantly improved outcomes in patients with metastatic non-small cell lung cancer (NSCLC) and are currently an established second-line therapeutic option. In this manuscript, we review the mechanism of action of checkpoint inhibitors, present the available data with approved and experimental agents, discuss the progress that has already been made in the field, as well as toxicity awareness, and future perspectives. PMID:27800034

  1. Potential Anti-metastasis Natural Compounds for Lung Cancer.

    PubMed

    Chanvorachote, Pithi; Chamni, Supakarn; Ninsontia, Chuanpit; Phiboonchaiyanan, Preeyaporn Plaimee

    2016-11-01

    As lung cancer is the most common malignancy worldwide and high mortalities are the result of metastasis, novel information surpassing the treatment strategies and therapeutic agents focusing on cancer dissemination are of interest. Lung cancer metastasis involves increased motility, survival in circulation and ability to form new tumors. Metastatic cells increase their aggressive features by utilizing several mechanisms to overcome hindrances of metastasis, including epithelial to mesenchymal transition (EMT), increased in cellular survival and migratory signals. Sufficient amounts of natural product-derived compounds have been shown to have promising anti-metastasis activities by suppressing key molecular features upholding such cell aggressiveness. The knowledge regarding molecular mechanisms rendering cell dissemination together with the anti-metastasis information of natural product-derived compounds may lead to development of novel therapeutic strategies. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  2. Interleukin-33 potentiates bleomycin-induced lung injury.

    PubMed

    Luzina, Irina G; Kopach, Pavel; Lockatell, Virginia; Kang, Phillip H; Nagarsekar, Ashish; Burke, Allen P; Hasday, Jeffrey D; Todd, Nevins W; Atamas, Sergei P

    2013-12-01

    The mechanisms of interstitial lung disease (ILD) remain incompletely understood, although recent observations have suggested an important contribution by IL-33. Substantial elevations in IL-33 expression were found in the lungs of patients with idiopathic pulmonary fibrosis and scleroderma lung disease, as well as in the bleomycin injury mouse model. Most of the observed IL-33 expression was intracellular and intranuclear, suggesting involvement of the full-length (fl) protein, but not of the proteolytically processed mature IL-33 cytokine. The effects of flIL-33 on mouse lungs were assessed independently and in combination with bleomycin injury, using recombinant adenovirus-mediated gene delivery. Bleomycin-induced changes were not affected by gene deficiency of the IL-33 receptor T1/ST2. Combined flIL-33 expression and bleomycin injury exerted a synergistic effect on pulmonary lymphocyte and collagen accumulation, which could be explained by synergistic regulation of the cytokines transforming growth factor-β, IL-6, monocyte chemotactic protein-1, macrophage inflammatory protein\\x{2013}1α, and tumor necrosis factor-α. By contrast, no increase in the levels of the Th2 cytokines IL-4, IL-5, or IL-13 was evident. Moreover, flIL-33 was found to increase the expression of several heat shock proteins (HSPs) significantly, and in particular HSP70, which is known to be associated with ILD. Thus, flIL-33 is a synergistic proinflammatory and profibrotic regulator that acts by stimulating the expression of several non-Th2 cytokines, and activates the expression of HSP70.

  3. Moving Back to the Future: Use of Organ Care System Lung for Lobectomy Before Lobar Lung Transplantation.

    PubMed

    Sabashnikov, Anton; Zeriouh, Mohamed; Mohite, Prashant N; Patil, Nikhil P; García-Sáez, Diana; Schmack, Bastian; Soresi, Simona; Dohmen, Pascal M; Popov, Aron-Frederik; Weymann, Alexander; Simon, André R; De Robertis, Fabio

    2016-07-13

    BACKGROUND Lung transplantation remains the gold standard treatment for patients with end-stage lung disease. Lobar lung transplantation allows for transplantation of size-mismatch donor lungs in small recipients; however, donor lung volume reduction represents a challenging surgical technique. In this paper we present our initial experience with bilateral lobectomy in donor lungs before lobar lung transplantation using normothermic perfusion on the Organ Care System (OCS) Lung. MATERIAL AND METHODS Specifics of the surgical technique for donor lung instrumentation on the OCS, lobar dissection on the OCS, and right and left donor lobectomies are presented in detail. RESULTS Potential advantages of the use of the OCS for lobectomy for lobar lung transplantation are described in this section. Donor lung volume reduction utilizing OCS appeared to be easier and safer compared to the conventional cold storage technique, due to continuous perfusion of the lungs with blood and well-distended vessels that offer the feel of live lobectomy. Moreover, the OCS represents a platform for donor organ assessment and optimization of its function before transplantation. CONCLUSIONS Donor lung volume reduction was safe and feasible utilizing the OCS, which could be a useful tool for volume reduction in cases of size mismatch. Further research is needed to evaluate early and long-term results after lobar lung transplantation using the OCS in clinical studies.

  4. p90 ribosomal S6 kinase: a potential therapeutic target in lung cancer.

    PubMed

    Poomakkoth, Noufira; Issa, Aya; Abdulrahman, Nabeel; Abdelaziz, Somaia Gamal; Mraiche, Fatima

    2016-01-14

    A global survey of cancer has shown that lung cancer is the most common cause of the new cancer cases and cancer deaths in men worldwide. The mortality from lung cancer is more than the combined mortality from breast, prostate and colorectal cancers. The two major histological types of lung cancer are non-small cell lung cancer (NSCLC) accounting for about 85 % of cases and small cell lung cancer accounting for 15 % of cases. NSCLC, the more prevalent form of lung cancer, is often diagnosed at an advanced stage and has a very poor prognosis. Many factors have been shown to contribute to the development of lung cancer in humans including tobacco smoking, exposure to environmental carcinogens (asbestos, or radon) and genetic factors. Despite the advances in treatment, lung cancer remains one of the leading causes of cancer death worldwide. Interestingly, the overall 5 year survival from lung cancer has not changed appreciably in the past 25 years. For this reason, novel and more effective treatments and strategies for NSCLC are critically needed. p90 ribosomal S6 kinase (RSK), a serine threonine kinase that lies downstream of the Ras-MAPK (mitogen activated protein kinase) cascade, has been demonstrated to be involved in the regulation of cell proliferation in various malignancies through indirect (e.g., modulation of transcription factors) or direct effects on the cell-cycle machinery. Increased expression of RSK has been demonstrated in various cancers, including lung cancer. This review focuses on the role of RSK in lung cancer and its potential therapeutic application.

  5. Asymmetric dimethylarginine potentiates lung inflammation in a mouse model of allergic asthma

    PubMed Central

    Klein, Elizabeth; Weigel, Jason; Buford, Mary C.; Holian, Andrij

    2010-01-01

    Nitric oxide (NO), formed by nitric oxide synthase (NOS), is an important mediator of lung inflammation in allergic asthma. Asymmetric dimethylarginine (ADMA), a competitive endogenous inhibitor of NOS, is metabolized by the enzyme dimethylarginine dimethylaminohydrolase (DDAH). Elevated ADMA has been shown to affect lung function in mice, and by inhibiting NOS it alters NO and reactive oxygen species production in mouse lung epithelial cells. However, the effects of altered ADMA levels during lung inflammation have not been explored. A model of allergen-induced airway inflammation was utilized in combination with the modulation of endogenous circulating ADMA levels in mice. Airway inflammation was assessed by quantifying inflammatory cell infiltrates in lung lavage and by histology. Lung DDAH expression was assessed by quantitative PCR and immunohistochemistry. Nitrite levels were determined in lung lavage fluid as a measure of NO production. iNOS expression was determined by immunohistochemistry, immunofluorescence, Western blot, and quantitative PCR. NF-κB binding activity was assessed by a transcription factor binding assay. Allergen-induced lung inflammation was potentiated in mice with elevated circulating ADMA and was reduced in mice overexpressing DDAH. Elevated ADMA reduced nitrite levels in lung lavage fluid in both allergen-challenged and control animals. ADMA increased iNOS expression in airway epithelial cells in vivo following allergen challenge and in vitro in stimulated mouse lung epithelial cells. ADMA also increased NF-κB binding activity in airway epithelial cells in vitro. These data support that ADMA may play a role in inflammatory airway diseases such as asthma through modulation of iNOS expression in lung epithelial cells. PMID:20889675

  6. Lung scintigraphy in differential diagnosis of peripheral lung cancer and community-acquired pneumonia

    SciTech Connect

    Krivonogov, Nikolay G.; Efimova, Nataliya Y. Zavadovsky, Konstantin W.; Lishmanov, Yuri B.

    2016-08-02

    Ventilation/perfusion lung scintigraphy was performed in 39 patients with verified diagnosis of community-acquired pneumonia (CAP) and in 14 patients with peripheral lung cancer. Ventilation/perfusion ratio, apical-basal gradients of ventilation (U/L(V)) and lung perfusion (U/L(P)), and alveolar capillary permeability of radionuclide aerosol were determined based on scintigraphy data. The study demonstrated that main signs of CAP were increases in ventilation/perfusion ratio, perfusion and ventilation gradient on a side of the diseased lung, and two-side increase in alveolar capillary permeability rate for radionuclide aerosol. Unlike this, scintigraphic signs of peripheral lung cancer comprise an increase in ventilation/perfusion ratio over 1.0 on a side of the diseased lung with its simultaneous decrease on a contralateral side, normal values of perfusion and ventilation gradients of both lungs, and delayed alveolar capillary clearance in the diseased lung compared with the intact lung.

  7. Lung scintigraphy in differential diagnosis of peripheral lung cancer and community-acquired pneumonia

    NASA Astrophysics Data System (ADS)

    Krivonogov, Nikolay G.; Efimova, Nataliya Y.; Zavadovsky, Konstantin W.; Lishmanov, Yuri B.

    2016-08-01

    Ventilation/perfusion lung scintigraphy was performed in 39 patients with verified diagnosis of community-acquired pneumonia (CAP) and in 14 patients with peripheral lung cancer. Ventilation/perfusion ratio, apical-basal gradients of ventilation (U/L(V)) and lung perfusion (U/L(P)), and alveolar capillary permeability of radionuclide aerosol were determined based on scintigraphy data. The study demonstrated that main signs of CAP were increases in ventilation/perfusion ratio, perfusion and ventilation gradient on a side of the diseased lung, and two-side increase in alveolar capillary permeability rate for radionuclide aerosol. Unlike this, scintigraphic signs of peripheral lung cancer comprise an increase in ventilation/perfusion ratio over 1.0 on a side of the diseased lung with its simultaneous decrease on a contralateral side, normal values of perfusion and ventilation gradients of both lungs, and delayed alveolar capillary clearance in the diseased lung compared with the intact lung.

  8. Lung Volume Reduction After Stereotactic Ablative Radiation Therapy of Lung Tumors: Potential Application to Emphysema

    SciTech Connect

    Binkley, Michael S.; Shrager, Joseph B.; Leung, Ann N.; Popat, Rita; Trakul, Nicholas; Atwood, Todd F.; Chaudhuri, Aadel; Maxim, Peter G.; Diehn, Maximilian; Loo, Billy W.

    2014-09-01

    Purpose: Lung volume reduction surgery (LVRS) improves dyspnea and other outcomes in selected patients with severe emphysema, but many have excessive surgical risk for LVRS. We analyzed the dose-volume relationship for lobar volume reduction after stereotactic ablative radiation therapy (SABR) of lung tumors, hypothesizing that SABR could achieve therapeutic volume reduction if applied in emphysema. Methods and Materials: We retrospectively identified patients treated from 2007 to 2011 who had SABR for 1 lung tumor, pre-SABR pulmonary function testing, and ≥6 months computed tomographic (CT) imaging follow-up. We contoured the treated lobe and untreated adjacent lobe(s) on CT before and after SABR and calculated their volume changes relative to the contoured total (bilateral) lung volume (TLV). We correlated lobar volume reduction with the volume receiving high biologically effective doses (BED, α/β = 3). Results: 27 patients met the inclusion criteria, with a median CT follow-up time of 14 months. There was no grade ≥3 toxicity. The median volume reduction of the treated lobe was 4.4% of TLV (range, −0.4%-10.8%); the median expansion of the untreated adjacent lobe was 2.6% of TLV (range, −3.9%-11.6%). The volume reduction of the treated lobe was positively correlated with the volume receiving BED ≥60 Gy (r{sup 2}=0.45, P=.0001). This persisted in subgroups determined by high versus low pre-SABR forced expiratory volume in 1 second, treated lobe CT emphysema score, number of fractions, follow-up CT time, central versus peripheral location, and upper versus lower lobe location, with no significant differences in effect size between subgroups. Volume expansion of the untreated adjacent lobe(s) was positively correlated with volume reduction of the treated lobe (r{sup 2}=0.47, P<.0001). Conclusions: We identified a dose-volume response for treated lobe volume reduction and adjacent lobe compensatory expansion after lung tumor SABR, consistent across

  9. Potential Lung Nodules Identification for Characterization by Variable Multistep Threshold and Shape Indices from CT Images

    PubMed Central

    Iqbal, Saleem; Iqbal, Khalid; Shaukat, Arslan; Khanum, Aasia

    2014-01-01

    Computed tomography (CT) is an important imaging modality. Physicians, surgeons, and oncologists prefer CT scan for diagnosis of lung cancer. However, some nodules are missed in CT scan. Computer aided diagnosis methods are useful for radiologists for detection of these nodules and early diagnosis of lung cancer. Early detection of malignant nodule is helpful for treatment. Computer aided diagnosis of lung cancer involves lung segmentation, potential nodules identification, features extraction from the potential nodules, and classification of the nodules. In this paper, we are presenting an automatic method for detection and segmentation of lung nodules from CT scan for subsequent features extraction and classification. Contribution of the work is the detection and segmentation of small sized nodules, low and high contrast nodules, nodules attached with vasculature, nodules attached to pleura membrane, and nodules in close vicinity of the diaphragm and lung wall in one-go. The particular techniques of the method are multistep threshold for the nodule detection and shape index threshold for false positive reduction. We used 60 CT scans of “Lung Image Database Consortium-Image Database Resource Initiative” taken by GE medical systems LightSpeed16 scanner as dataset and correctly detected 92% nodules. The results are reproducible. PMID:25506388

  10. Potential lung nodules identification for characterization by variable multistep threshold and shape indices from CT images.

    PubMed

    Iqbal, Saleem; Iqbal, Khalid; Arif, Fahim; Shaukat, Arslan; Khanum, Aasia

    2014-01-01

    Computed tomography (CT) is an important imaging modality. Physicians, surgeons, and oncologists prefer CT scan for diagnosis of lung cancer. However, some nodules are missed in CT scan. Computer aided diagnosis methods are useful for radiologists for detection of these nodules and early diagnosis of lung cancer. Early detection of malignant nodule is helpful for treatment. Computer aided diagnosis of lung cancer involves lung segmentation, potential nodules identification, features extraction from the potential nodules, and classification of the nodules. In this paper, we are presenting an automatic method for detection and segmentation of lung nodules from CT scan for subsequent features extraction and classification. Contribution of the work is the detection and segmentation of small sized nodules, low and high contrast nodules, nodules attached with vasculature, nodules attached to pleura membrane, and nodules in close vicinity of the diaphragm and lung wall in one-go. The particular techniques of the method are multistep threshold for the nodule detection and shape index threshold for false positive reduction. We used 60 CT scans of "Lung Image Database Consortium-Image Database Resource Initiative" taken by GE medical systems LightSpeed16 scanner as dataset and correctly detected 92% nodules. The results are reproducible.

  11. Lung Ultrasound in the Management of Fluid Volume in Dialysis Patients: Potential Usefulness.

    PubMed

    Zoccali, Carmine

    2017-01-01

    Volume overload is a hidden, pervasive complication in dialysis patients with dyspnea and pulmonary edema being its main clinical manifestations. Measuring lung water has clinical potential because it allows timely treatment of lung congestion at a preclinical stage. Chest ultrasound (US) is a novel, well-validated technique that allows reliable estimates of lung water in clinical practice. The application of this technique in dialysis patients has shown that an unsuspectedly high proportion of these patients have moderate to severe lung congestion which is usually asymptomatic. Furthermore, lung congestion in these patients is only loosely associated with fluid excess as measured by bioimpedance (BIA). Lung congestion is associated with a high death risk in dialysis patients and therefore represents a potential treatment target. The "Lung water by Ultra-Sound guided Treatment to prevent death and cardiovascular complications in high risk ESRD patients with cardiomyopathy" (LUST) study will provide important information about the clinical value of this technique in the care of hemodialysis patients at high cardiovascular risk.

  12. [New techniques and potential benefits for radiotherapy of lung cancer].

    PubMed

    Lefebvre, L; Doré, M; Giraud, P

    2014-10-01

    Radiotherapy is used for inoperable lung cancers, sometimes in association with chemotherapy. Outcomes of conventional radiotherapy are disappointing. New techniques improve adaptation to tumour volume, decrease normal tissue irradiation and lead to increasing tumour dose with the opportunity for improved survival. With intensity-modulated radiation therapy, isodoses can conform to complex volumes. It is widely used and seems to be indicated in locally advanced stages. Its dosimetric improvements have been demonstrated but outcomes are still heterogeneous. Stereotactic radiotherapy allows treatment of small volumes with many narrow beams. Dedicated devices or appropriate equipment on classical devices are needed. In early stages, its efficacy is comparable to surgery with an acceptable toxicity. Endobronchial brachytherapy could be used for early stages with specific criteria. Hadrontherapy is still experimental regarding lung cancer. Hadrons have physical properties leading to very accurate dose distribution. In the rare published studies, toxicities are roughly lower than others techniques but for early stages its effectiveness is not better than stereotactic radiotherapy. These techniques are optimized by metabolic imaging which precisely defines the target volume and assesses the therapeutic response; image-guided radiation therapy which allows a more accurate patient set up and by respiratory tracking or gating which takes account of tumour respiratory motions.

  13. Lung cancer and β-glucans: review of potential therapeutic applications.

    PubMed

    Roudi, Raheleh; Mohammadi, Shahla Roudbar; Roudbary, Maryam; Mohsenzadegan, Monireh

    2017-03-16

    The potential of natural substances with immunotherapeutic properties has long been studied. β-glucans, a cell wall component of certain bacteria and fungi, potentiate the immune system against microbes and toxic substances. Moreover, β-glucans are known to exhibit direct anticancer effects and can suppress cancer proliferation through immunomodulatory pathways. Mortality of lung cancer has been alarmingly increasingly worldwide; therefore, treatment of lung cancer is an urgent necessity. Numerous researchers are now dedicated to using β-glucans as a therapy for lung cancer. In the present attempt, we have reviewed the studies addressing therapeutic effects of β-glucans in primary and metastatic lung cancer published in the time period of 1991-2016.

  14. Synthesis and surface activity of diether-linked phosphoglycerols: potential applications for exogenous lung surfactants.

    PubMed

    Notter, Robert H; Wang, Zhongyi; Wang, Zhengdong; Davy, Jason A; Schwan, Adrian L

    2007-01-01

    The synthesis of three phosphoglycerols is described, one of which contains the previously unknown phosphonoglycerol headgroup. The surface tension-lowering capabilities of synthetic lung surfactant mixtures containing the PG analogs were measured on the pulsating bubble surfactometer and compared to known controls. The PG-containing mixtures exhibited superior surface tension-lowering properties indicating the significant potential of these analogs as components in synthetic exogenous lung surfactants.

  15. Potentially estrogenic polychlorinated biphenyls congeners serum levels and its relation with lung cancer.

    PubMed

    Recio-Vega, Rogelio; Mendez-Henandez, Alejandra; Gabriel, Antonio Padua Y; Jacobo-Avila, Antonio; Portales-Castanedo, Arnulfo; Hernandez-Gonzalez, Sandra; Gallegos-Arreola, Martha Patricia; Ocampo-Gomez, Guadalupe

    2013-09-01

    Lung cancer is the most common cancer in the world. The main cause of lung cancer is cigarette smoke; however, other important genetic and environmental risk factors play a significant role in the development of lung cancer. Among these factors, occupational and accidental exposure to polychlorinated biphenyls (PCBs) has been associated with an increased risk in lung cancer, suggesting that PCBs could be potent carcinogens. The aim of the present study was to investigate the association between PCB exposure levels, CYP1A1 polymorphisms and the risk of lung cancer. This study enrolled newly diagnosed lung cancer patients. Environmental and occupational information related to the patients studied was collected. Blood samples were taken for the measurement of serum levels of 20 PCB congeners and for CYP1A1 polymorphism analysis. The serum levels of two PCB congeners with potential estrogenic activity were higher in lung cancer patients. The risk of lung cancer was found to correlate with age, gender, smoking history and with agricultural workers, as well as with congener 18. No differences were found in the frequency of CYP1A1 polymorphisms. Furthermore, we did not find a correlation between CYP1A1 polymorphisms and PCB serum levels. The high levels of PCB with estrogenic activity found in our cases, could promote lung cancer inducing cell proliferation in non-neoplastic and neoplastic lung cells via ERβ; inducing the formation of DNA adducts, producing oxidative stress with the subsequent DNA damage and increasing the endogenous catechol levels by catechol-O-methyl transferase (COMT) inhibition. Copyright © 2012 John Wiley & Sons, Ltd.

  16. Can pulmonary angiography be limited to the most suspicious side if the contralateral side appears normal on the ventilation/perfusion lung scan? Data from PIOPED. Prospective Investigation of Pulmonary Embolism Diagnosis.

    PubMed

    Gottschalk, A; Stein, P D; Henry, J W; Relyea, B

    1996-08-01

    The purpose of this investigation was to determine the frequency of pulmonary embolism (PE) in a single lung that showed a normal ventilation/perfusion (V/Q) lung scan when the V/Q scan on the contralateral side was interpreted as non-high-probability for PE. Data are from the national collaborative study Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED). PE was diagnosed or excluded in all lungs by pulmonary angiography. Single lungs with no V/Q abnormalities, when the V/Q scan on the contralateral side was interpreted as non-high-probability for PE, showed PE in 2 of 19 (11%) (95% confidence interval [CI], 1 to 33%). If PE was excluded by angiography on the side of the abnormal V/Q scan, then PE on the side of the normal V/Q scan was shown in only 1 of 19 (5%) (95% CI, 0 to 26%). A normal V/Q scan in a single lung, when the contralateral lung was interpreted as non-high-probability for PE, did not completely exclude PE on the apparently normal side. In such lungs, the probability of PE was in the range of low-probability interpretations. If the pulmonary angiogram showed no PE on the side of the abnormal V/Q scan, the probability of PE on the side of the normal V/Q scan satisfied the definition of very low probability for PE. This observation in patients undergoing pulmonary angiography may assist in determining whether the pulmonary angiogram should be bilateral.

  17. Estimation of optimal b-value sets for obtaining apparent diffusion coefficient free from perfusion in non-small cell lung cancer.

    PubMed

    Karki, Kishor; Hugo, Geoffrey D; Ford, John C; Olsen, Kathryn M; Saraiya, Siddharth; Groves, Robert; Weiss, Elisabeth

    2015-10-21

    The purpose of this study was to determine optimal sets of b-values in diffusion-weighted MRI (DW-MRI) for obtaining monoexponential apparent diffusion coefficient (ADC) close to perfusion-insensitive intravoxel incoherent motion (IVIM) model ADC (ADCIVIM) in non-small cell lung cancer. Ten subjects had 40 DW-MRI scans before and during radiotherapy in a 1.5 T MRI scanner. Respiratory triggering was applied to the echo-planar DW-MRI with TR ≈ 4500 ms, TE  =  74 ms, eight b-values of 0-1000 μs μm(-2), pixel size  =  1.98 × 1.98 mm(2), slice thickness  =  6 mm, interslice gap  =  1.2 mm, 7 axial slices and total acquisition time ≈6 min. One or more DW-MRI scans together covered the whole tumour volume. Monoexponential model ADC values using various b-value sets were compared to reference-standard ADCIVIM values using all eight b-values. Intra-scan coefficient of variation (CV) of active tumour volumes was computed to compare the relative noise in ADC maps. ADC values for one pre-treatment DW-MRI scan of each of the 10 subjects were computed using b-value pairs from DW-MRI images synthesized for b-values of 0-2000 μs μm(-2) from the estimated IVIM parametric maps and corrupted by various Rician noise levels. The square root of mean of squared error percentage (RMSE) of the ADC value relative to the corresponding ADCIVIM for the tumour volume of the scan was computed. Monoexponential ADC values for the b-value sets of 250 and 1000; 250, 500 and 1000; 250, 650 and 1000; 250, 800 and 1000; and 250-1000 μs μm(-2) were not significantly different from ADCIVIM values (p > 0.05, paired t-test). Mean error in ADC values for these sets relative to ADCIVIM were within 3.5%. Intra-scan CVs for these sets were comparable to that for ADCIVIM. The monoexponential ADC values for other sets-0-1000; 50-1000; 100-1000; 500-1000; and 250 and 800 μs μm(-2) were significantly different from the ADCIVIM values. From Rician noise

  18. Estimation of optimal b-value sets for obtaining apparent diffusion coefficient free from perfusion in non-small cell lung cancer

    NASA Astrophysics Data System (ADS)

    Karki, Kishor; Hugo, Geoffrey D.; Ford, John C.; Olsen, Kathryn M.; Saraiya, Siddharth; Groves, Robert; Weiss, Elisabeth

    2015-10-01

    The purpose of this study was to determine optimal sets of b-values in diffusion-weighted MRI (DW-MRI) for obtaining monoexponential apparent diffusion coefficient (ADC) close to perfusion-insensitive intravoxel incoherent motion (IVIM) model ADC (ADCIVIM) in non-small cell lung cancer. Ten subjects had 40 DW-MRI scans before and during radiotherapy in a 1.5 T MRI scanner. Respiratory triggering was applied to the echo-planar DW-MRI with \\text{TR}≈ 4500 ms, TE  =  74 ms, eight b-values of 0-1000 μs μm-2, pixel size  =  1.98× 1.98 mm2, slice thickness  =  6 mm, interslice gap  =  1.2 mm, 7 axial slices and total acquisition time ≈6 min. One or more DW-MRI scans together covered the whole tumour volume. Monoexponential model ADC values using various b-value sets were compared to reference-standard ADCIVIM values using all eight b-values. Intra-scan coefficient of variation (CV) of active tumour volumes was computed to compare the relative noise in ADC maps. ADC values for one pre-treatment DW-MRI scan of each of the 10 subjects were computed using b-value pairs from DW-MRI images synthesized for b-values of 0-2000 μs μm-2 from the estimated IVIM parametric maps and corrupted by various Rician noise levels. The square root of mean of squared error percentage (RMSE) of the ADC value relative to the corresponding ADCIVIM for the tumour volume of the scan was computed. Monoexponential ADC values for the b-value sets of 250 and 1000; 250, 500 and 1000; 250, 650 and 1000; 250, 800 and 1000; and 250-1000 μs μm-2 were not significantly different from ADCIVIM values (p>0.05 , paired t-test). Mean error in ADC values for these sets relative to ADCIVIM were within 3.5%. Intra-scan CVs for these sets were comparable to that for ADCIVIM. The monoexponential ADC values for other sets—0-1000 50-1000 100-1000 500-1000 and 250 and 800 μs μm-2 were significantly different from the ADCIVIM values. From Rician noise simulation

  19. Measurement of extravascular lung water using the single indicator method in patients: research and potential clinical value

    PubMed Central

    Liu, Kathleen D.; Matthay, Michael A.

    2009-01-01

    Extravascular lung water includes all of the fluid within the lung but outside of the vasculature. Lung water increases as a result of increased hydrostatic vascular pressure or from an increase in lung endothelial and epithelial permeability or both. Experimentally, extravascular lung water has been measured gravimetrically. Clinically, the chest radiograph is used to determine whether extravascular lung water is present but is an insensitive instrument for determining the quantity of lung water. Bedside measurement of extravascular lung water in patients is now possible using a single indicator thermodilution method. This review critically evaluates the experimental and clinical evidence supporting the potential value of measuring extravascular lung water in patients using the single indicator method. PMID:19617309

  20. Measurement of extravascular lung water using the single indicator method in patients: research and potential clinical value.

    PubMed

    Brown, Lisa M; Liu, Kathleen D; Matthay, Michael A

    2009-10-01

    Extravascular lung water includes all of the fluid within the lung but outside of the vasculature. Lung water increases as a result of increased hydrostatic vascular pressure or from an increase in lung endothelial and epithelial permeability or both. Experimentally, extravascular lung water has been measured gravimetrically. Clinically, the chest radiograph is used to determine whether extravascular lung water is present but is an insensitive instrument for determining the quantity of lung water. Bedside measurement of extravascular lung water in patients is now possible using a single indicator thermodilution method. This review critically evaluates the experimental and clinical evidence supporting the potential value of measuring extravascular lung water in patients using the single indicator method.

  1. Therapeutic potential of lung epithelial progenitor cells derived from embryonic and induced pluripotent stem cells.

    PubMed

    Wetsel, Rick A; Wang, Dachun; Calame, Daniel G

    2011-01-01

    Embryonic stem (ES) cells derived from preimplantation blastocysts and induced pluripotent stem (iPS) cells generated from somatic cell sources are pluripotent and capable of indefinite expansion in vitro. They provide a possible unlimited source of cells that could be differentiated into lung progenitor cells for potential clinical use in pulmonary regenerative medicine. Because of inherent difficulties in deriving endodermal cells from undifferentiated cell cultures, applications using lung epithelial cells derived from ES and iPS cells have lagged behind similar efforts devoted to other tissues, such as the heart and spinal cord. However, during the past several years, significant advances in culture, differentiation, and purification protocols, as well as in bioengineering methodologies, have fueled enthusiasm for the development of stem cell-based lung therapeutics. This article provides an overview of recent research achievements and discusses future technical challenges that must be met before the promise of stem cell applications for lung disease can be realized.

  2. Therapeutic Potential of Lung Epithelial Progenitor Cells Derived from Embryonic and Induced Pluripotent Stem Cells

    PubMed Central

    Wetsel, Rick A.; Wang, Dachun; Calame, Daniel G.

    2015-01-01

    Embryonic stem (ES) cells derived from preimplantation blastocysts and induced pluripotent stem (iPS) cells generated from somatic cell sources are pluripotent and capable of indefinite expansion in vitro. They provide a possible unlimited source of cells that could be differentiated into lung progenitor cells for potential clinical use in pulmonary regenerative medicine. Because of inherent difficulties in deriving endodermal cells from undifferentiated cell cultures, applications using lung epithelial cells derived from ES and iPS cells have lagged behind similar efforts devoted to other tissues, such as the heart and spinal cord. However, during the past several years, significant advances in culture, differentiation, and purification protocols, as well as in bioengineering methodologies, have fueled enthusiasm for the development of stem cell–based lung therapeutics. This article provides an overview of recent research achievements and discusses future technical challenges that must be met before the promise of stem cell applications for lung disease can be realized. PMID:21226612

  3. The potential for resident lung mesenchymal stem cells to promote functional tissue regeneration: understanding microenvironmental cues.

    PubMed

    Foronjy, Robert F; Majka, Susan M

    2012-12-01

    Tissue resident mesenchymal stem cells (MSCs) are important regulators of tissue repair or regeneration, fibrosis, inflammation, angiogenesis and tumor formation. Bone marrow derived mesenchymal stem cells (BM-MSCs) and endothelial progenitor cells (EPC) are currently being considered and tested in clinical trials as a potential therapy in patients with such inflammatory lung diseases including, but not limited to, chronic lung disease, pulmonary arterial hypertension (PAH), pulmonary fibrosis (PF), chronic obstructive pulmonary disease (COPD)/emphysema and asthma. However, our current understanding of tissue resident lung MSCs remains limited. This review addresses how environmental cues impact on the phenotype and function of this endogenous stem cell pool. In addition, it examines how these local factors influence the efficacy of cell-based treatments for lung diseases.

  4. Machine perfusion in organ transplantation: a tool for ex-vivo graft conditioning with mesenchymal stem cells?

    PubMed

    Van Raemdonck, Dirk; Neyrinck, Arne; Rega, Filip; Devos, Timothy; Pirenne, Jacques

    2013-02-01

    Machine perfusion has emerged as a tool to evaluate pretransplant graft function more objectively during preservation. Machine perfusion also offers the possibility to recondition questionable organs and to 'immunomodulate' allografts ex vivo. This article aims to review the current knowledge on machine perfusion of the various solid thoracic and abdominal organs, and to discuss the new possibility of conditioning and treating grafts with mesenchymal stem cells (MSCs) during machine perfusion. Different methods of machine perfusion have been described varying among organs in temperature and composition of perfusate. Commercial devices have recently become available for machine perfusion of all organs, with the largest clinical experience acquired in kidney and lung transplantation. Clinical studies are ongoing for liver, heart, and pancreas. MSC therapy in organ transplantation is now emerging with clinical studies set up to investigate its potential to attenuate ischemia/reperfusion injury (innate immunity) and to downregulate the alloimmune response (adaptive immunity) and promote engraftment after transplantation. We hypothesize that delivery of MSCs directly into the machine perfusion circuit may provide a unique opportunity to treat and immunomodulate organs prior to transplantation. To our knowledge, no study on ex-vivo delivery of MSCs during machine perfusion has been reported. Machine perfusion of solid organs has regained much attention during the last decade. It provides a new promising tool that may allow pretransplant ex-vivo assessment, preservation, repair, and conditioning of grafts. Experimental research and clinical trials testing the administration of MSCs during machine perfusion are warranted to explore the potential benefit and mechanisms of this approach.

  5. Potential Metabolic Biomarkers to Identify Interstitial Lung Abnormalities

    PubMed Central

    Tan, Yong; Jia, Dongmei; Lin, Zhang; Guo, Baosheng; He, Bing; Lu, Cheng; Xiao, Cheng; Liu, Zhongdi; Zhao, Ning; Bian, Zhaoxiang; Zhang, Ge; Zhang, Weidong; Liu, Xinru; Lu, Aiping

    2016-01-01

    Determining sensitive biomarkers in the peripheral blood to identify interstitial lung abnormalities (ILAs) is essential for the simple early diagnosis of ILAs. This study aimed to determine serum metabolic biomarkers of ILAs and the corresponding pathogenesis. Three groups of subjects undergoing health screening, including healthy subjects, subjects with ILAs, and subjects who were healthy initially and with ILAs one year later (Healthy→ILAs), were recruited for this study. The metabolic profiles of all of the subjects’ serum were analyzed by liquid chromatography quadruple time-of-flight mass spectrometry. The metabolic characteristics of the ILAs subjects were discovered, and the corresponding biomarkers were predicted. The metabolomic data from the Healthy→ILAs subjects were collected for further verification. The results indicated that five serum metabolite alterations (up-regulated phosphatidylcholine, phosphatidic acid, betaine aldehyde and phosphatidylethanolamine, as well as down-regulated 1-acylglycerophosphocholine) were sensitive and reliable biomarkers for identifying ILAs. Perturbation of the corresponding biological pathways (RhoA signaling, mTOR/P70S6K signaling and phospholipase C signaling) might be at least partially responsible for the pathogenesis of ILAs. This study may provide a good template for determining the early diagnostic markers of subclinical disease status and for obtaining a better understanding of their pathogenesis. PMID:27438829

  6. Single-energy computed tomography-based pulmonary perfusion imaging: Proof-of-principle in a canine model

    PubMed Central

    Yamamoto, Tokihiro; Kent, Michael S.; Wisner, Erik R.; Johnson, Lynelle R.; Stern, Joshua A.; Qi, Lihong; Fujita, Yukio; Boone, John M.

    2016-01-01

    Purpose: Radiotherapy (RT) that selectively avoids irradiating highly functional lung regions may reduce pulmonary toxicity, which is substantial in lung cancer RT. Single-energy computed tomography (CT) pulmonary perfusion imaging has several advantages (e.g., higher resolution) over other modalities and has great potential for widespread clinical implementation, particularly in RT. The purpose of this study was to establish proof-of-principle for single-energy CT perfusion imaging. Methods: Single-energy CT perfusion imaging is based on the following: (1) acquisition of end-inspiratory breath-hold CT scans before and after intravenous injection of iodinated contrast agents, (2) deformable image registration (DIR) for spatial mapping of those two CT image data sets, and (3) subtraction of the precontrast image data set from the postcontrast image data set, yielding a map of regional Hounsfield unit (HU) enhancement, a surrogate for regional perfusion. In a protocol approved by the institutional animal care and use committee, the authors acquired CT scans in the prone position for a total of 14 anesthetized canines (seven canines with normal lungs and seven canines with diseased lungs). The elastix algorithm was used for DIR. The accuracy of DIR was evaluated based on the target registration error (TRE) of 50 anatomic pulmonary landmarks per subject for 10 randomly selected subjects as well as on singularities (i.e., regions where the displacement vector field is not bijective). Prior to perfusion computation, HUs of the precontrast end-inspiratory image were corrected for variation in the lung inflation level between the precontrast and postcontrast end-inspiratory CT scans, using a model built from two additional precontrast CT scans at end-expiration and midinspiration. The authors also assessed spatial heterogeneity and gravitationally directed gradients of regional perfusion for normal lung subjects and diseased lung subjects using a two-sample two-tailed t

  7. Single-energy computed tomography-based pulmonary perfusion imaging: Proof-of-principle in a canine model.

    PubMed

    Yamamoto, Tokihiro; Kent, Michael S; Wisner, Erik R; Johnson, Lynelle R; Stern, Joshua A; Qi, Lihong; Fujita, Yukio; Boone, John M

    2016-07-01

    Radiotherapy (RT) that selectively avoids irradiating highly functional lung regions may reduce pulmonary toxicity, which is substantial in lung cancer RT. Single-energy computed tomography (CT) pulmonary perfusion imaging has several advantages (e.g., higher resolution) over other modalities and has great potential for widespread clinical implementation, particularly in RT. The purpose of this study was to establish proof-of-principle for single-energy CT perfusion imaging. Single-energy CT perfusion imaging is based on the following: (1) acquisition of end-inspiratory breath-hold CT scans before and after intravenous injection of iodinated contrast agents, (2) deformable image registration (DIR) for spatial mapping of those two CT image data sets, and (3) subtraction of the precontrast image data set from the postcontrast image data set, yielding a map of regional Hounsfield unit (HU) enhancement, a surrogate for regional perfusion. In a protocol approved by the institutional animal care and use committee, the authors acquired CT scans in the prone position for a total of 14 anesthetized canines (seven canines with normal lungs and seven canines with diseased lungs). The elastix algorithm was used for DIR. The accuracy of DIR was evaluated based on the target registration error (TRE) of 50 anatomic pulmonary landmarks per subject for 10 randomly selected subjects as well as on singularities (i.e., regions where the displacement vector field is not bijective). Prior to perfusion computation, HUs of the precontrast end-inspiratory image were corrected for variation in the lung inflation level between the precontrast and postcontrast end-inspiratory CT scans, using a model built from two additional precontrast CT scans at end-expiration and midinspiration. The authors also assessed spatial heterogeneity and gravitationally directed gradients of regional perfusion for normal lung subjects and diseased lung subjects using a two-sample two-tailed t-test. The mean TRE

  8. Xanthine oxidase inhibition attenuates ischemic-reperfusion lung injury

    SciTech Connect

    Lynch, M.J.; Grum, C.M.; Gallagher, K.P.; Bolling, S.F.; Deeb, G.M.; Morganroth, M.L.

    1988-05-01

    Ischemic-reperfusion lung injury is a factor potentially limiting the usefulness of distant organ procurement for heart-lung transplantation. Toxic oxygen metabolites are considered a major etiologic factor in reperfusion injury. Although oxygen-free radicals may be generated by many mechanisms, we investigated the role of xanthine oxidase in this injury process by using lodoxamide, a xanthine oxidase inhibitor, to inhibit ischemic-reperfusion injury in an isolated rat lung model. Isolated rat lungs were perfused with physiologic salt solution (PSS) osmotically stabilized with Ficoll until circulating blood elements were nondetectable in the pulmonary venous effluent. Lungs were rendered ischemic by interrupting ventilation and perfusion for 2 hr at 37/sup 0/C. After the ischemic interval, the lungs were reperfused with whole blood and lung injury was determined by measuring the accumulation of /sup 125/I-bovine serum albumin in lung parenchyma and alveolar lavage fluid as well as by gravimetric measurements. Lung effluent was collected immediately pre- and postischemia for analysis of uric acid by high-pressure liquid chromatography. Lodoxamide (1 mM) caused significant attenuation of postischemic lung injury. Uric acid levels in the lung effluent confirmed inhibition of xanthine oxidase. Protection from injury was not complete, however, implying that additional mechanisms may contribute to ischemic-reperfusion injury in the lung.

  9. Magnetic resonance imaging in lung: a review of its potential for radiotherapy

    PubMed Central

    Liney, Gary; Rai, Robba; Holloway, Lois; Moses, Daniel; Vinod, Shalini K

    2016-01-01

    MRI has superior soft-tissue definition compared with existing imaging modalities in radiation oncology; this has the added benefit of functional as well as anatomical imaging. This review aimed to evaluate the current use of MRI for lung cancer and identify the potential of a MRI protocol for lung radiotherapy (RT). 30 relevant studies were identified. Improvements in MRI technology have overcome some of the initial limitations of utilizing MRI for lung imaging. A number of commercially available and novel sequences have shown image quality to be adequate for the detection of pulmonary nodules with the potential for tumour delineation. Quantifying tumour motion is also feasible and may be more representative than that seen on four-dimensional CT. Functional MRI sequences have shown correlation with flu-deoxy-glucose positron emission tomography (FDG-PET) in identifying malignant involvement and treatment response. MRI can also be used as a measure of pulmonary function. While there are some limitations for the adoption of MRI in RT-planning process for lung cancer, MRI has shown the potential to compete with both CT and PET for tumour delineation and motion definition, with the added benefit of functional information. MRI is well placed to become a significant imaging modality in RT for lung cancer. PMID:26838950

  10. Low local blood perfusion, high white blood cell and high platelet count are associated with primary tumor growth and lung metastasis in a 4T1 mouse breast cancer metastasis model.

    PubMed

    Wang, Chuan; Chen, Ying-Ge; Gao, Jian-Li; Lyu, Gui-Yuan; Su, Jie; Zhang, Q I; Ji, Xin; Yan, Ji-Zhong; Qiu, Qiao-Li; Zhang, Yue-Li; Li, Lin-Zi; Xu, Han-Ting; Chen, Su-Hong

    2015-08-01

    It was originally thought that no single routine blood test result would be able to indicate whether or not a patient had cancer; however, several novel studies have indicated that the median survival and prognosis of cancer patients were markedly associated with the systemic circulation features of cancer patients. In addition, certain parameters, such as white blood cell (WBC) count, were largely altered in malignant tumors. In the present study, routine blood tests were performed in order to observe the change of blood cells in tumor-bearing mice following the implantation of 4T1 breast cancer cells into the mammary fat pad; in addition, blood flow in breast tumor sites was measured indirectly using laser Doppler perfusion imaging (LDPI), in an attempt to explain the relevance between the blood circulation features and the growth or metastasis of breast cancer in mice model. The LDPI and blood test results indicated that the implantation of 4T1 breast cancer cells into BALB/c mice led to thrombosis as well as high WBC count, high platelet count, high plateletcrit and low blood perfusion. Following implantation of the 4T1 cells for four weeks, the lung metastatic number was determined and the Pearson correlation coefficient revealed that the number of visceral lung metastatic sites had a marked negative association with the ratio of basophils (BASO%; r=-0.512; P<0.01) and the mean corpuscular hemoglobin was significantly correlated with primary tumor weight (r=0.425; P<0.05). In conclusion, the results of the present study demonstrated that tumor growth led to thrombosis and acute anemia in mice; in addition, when blood BASO% was low, an increased number of lung metastases were observed in tumor-bearing mice.

  11. Focal iodine defects on color-coded iodine perfusion maps of dual-energy pulmonary CT angiography images: a potential diagnostic pitfall.

    PubMed

    Kang, Mi-Jin; Park, Chang Min; Lee, Chang-Hyun; Goo, Jin Mo; Lee, Hyun Ju

    2010-11-01

    The purpose of this article is to systematically investigate focal iodine defects found in patients without other CT evidence for pulmonary embolism on color-coded iodine perfusion maps of dual-energy pulmonary CT angiography scans. Forty-three patients (mean age, 56.9 years; range, 29-88 years) who underwent pulmonary CT angiography using dual-energy CT from November 2007 to February 2008 but who had no pulmonary embolism were included in our study. Dark orange- or black-colored areas on color-coded iodine perfusion maps were interpreted as focal iodine defects. Two radiologists recorded the presence, location, and characteristics of the focal iodine defects in consensus and evaluated the examinations with regard to the causes of the focal iodine defects. Focal iodine defects were found in 41 patients (95%). The most commonly involved segments were the anterior segment of the right upper lobe (33/38, 86.8%), the apical segment of the right upper lobe (32/38, 84.2%), the medial segment of the right middle lobe (32/38, 84.2%), the apicoposterior segment of the left upper lobe (35/42, 83.3%), the superior and inferior lingular segments of the left upper lobe (23/42, 54.8%), and the medial-basal segment of the right lower lobe (11/32, 34.4%). Beam-hardening artifacts caused by contrast material in the superior vena cava accounted for nearly all defects in the apices of both upper lobes. Cardiac motion was the most common cause of defects in right middle lobe and left upper lobe lingular segments, and diaphragmatic motion was the most common cause in the lung bases. Knowledge of the focal iodine defects not related to pulmonary embolism leads to more accurate interpretation of dual-energy pulmonary CT angiography scans.

  12. Identification of ubiquinol cytochrome c reductase hinge (UQCRH) as a potential diagnostic biomarker for lung adenocarcinoma

    PubMed Central

    Gao, Feng; Liu, Qicai; Li, Guoping; Dong, Feng; Qiu, Minglian; Lv, Xiaoting; Zhang, Sheng; Guo, Zheng

    2016-01-01

    Ubiquinol cytochrome c reductase hinge (UQCRH) is a novel protein that localizes in the mitochondrial membrane and induces mitochondrial reactive oxygen species (ROS) generation. It had a high expression rate of 87.10% (108/124) in lung adenocarcinoma. Moreover, serum UQCRH level in patients with lung adenocarcinoma was significantly increased compared with that of pneumonia patients (p < 0.0001) and normal control subjects (p < 0.0001). Receiver operating characteristic curve analysis using an optimal cut-off value of 162.65 pg ml−1 revealed sensitivity and specificity for the diagnosis of lung adenocarcinoma of 88.7% and 85.7%, respectively, with an area under the curve of 0.927 (95% CI: 0.892 to 0.962, p < 0.0001). Serum UQCRH discriminates lung adenocarcinoma patients from the population without cancer with considerable sensitivity and specificity, but it does not distinguish between heavy smokers and lung adenocarcinoma patients. Serum UQCRH could be a potential diagnostic biomarker for lung adenocarcinoma. PMID:27358292

  13. Potential of the SPY intraoperative perfusion assessment system to reduce ischemic complications in immediate postmastectomy breast reconstruction

    PubMed Central

    2013-01-01

    Background The quality and viability of mastectomy flaps remain a central challenge in reconstructive surgery, particularly for immediate breast reconstruction. Insufficient perfusion in tissue flaps is a leading cause of early complications following reconstructive procedures, and clinical judgment alone is not completely reliable for the assessment of flap viability. Accurate and reliable intraoperative methods for assessment of tissue perfusion are needed to help surgeons identify tissue at risk for ischemia and necrosis, thereby allowing for maneuvers to improve tissue flap viability. Methods This study evaluates the use of intraoperative laser angiography using the SPY System (LifeCell Corp., Branchburg, NJ) for the assessment of perfusion in mastectomy flaps for immediate breast reconstruction. The SPY System uses the contrast agent indocyanine green, which has an excellent safety profile and pharmacokinetics that allow for repeat evaluations during the same surgical procedure. In recent work, the SPY System has demonstrated high sensitivity and specificity for detection of tissues at risk for ischemia and necrosis during reconstructive surgery. Using a retrospective, chart-review design, the authors compared consecutive cases of immediate breast reconstruction using a prosthesis, before and after implementation of the SPY System. Results Ninety-one subjects were included in the analysis: 52 prior to SPY (Pre-SPY) and 39 after implementation of SPY (Post-SPY). Baseline characteristics were similar between the groups. Both groups had high rates of comorbidities, chemotherapy, and radiation therapy. The rate of postoperative complications was two-fold higher in the Pre-SPY group compared to the Post-SPY group (36.5% vs. 17.9%); this difference was of borderline significance (P = 0.0631). However, mean number of repeat visits to the OR per patient was significantly higher in the Pre-SPY group (1.21 ± 1.47 vs. 0.41 ± 0.71; P = 0.0023). Of the

  14. Potential of the SPY intraoperative perfusion assessment system to reduce ischemic complications in immediate postmastectomy breast reconstruction.

    PubMed

    Sood, Mohit; Glat, Paul

    2013-07-23

    The quality and viability of mastectomy flaps remain a central challenge in reconstructive surgery, particularly for immediate breast reconstruction. Insufficient perfusion in tissue flaps is a leading cause of early complications following reconstructive procedures, and clinical judgment alone is not completely reliable for the assessment of flap viability. Accurate and reliable intraoperative methods for assessment of tissue perfusion are needed to help surgeons identify tissue at risk for ischemia and necrosis, thereby allowing for maneuvers to improve tissue flap viability. This study evaluates the use of intraoperative laser angiography using the SPY System (LifeCell Corp., Branchburg, NJ) for the assessment of perfusion in mastectomy flaps for immediate breast reconstruction. The SPY System uses the contrast agent indocyanine green, which has an excellent safety profile and pharmacokinetics that allow for repeat evaluations during the same surgical procedure. In recent work, the SPY System has demonstrated high sensitivity and specificity for detection of tissues at risk for ischemia and necrosis during reconstructive surgery. Using a retrospective, chart-review design, the authors compared consecutive cases of immediate breast reconstruction using a prosthesis, before and after implementation of the SPY System. Ninety-one subjects were included in the analysis: 52 prior to SPY (Pre-SPY) and 39 after implementation of SPY (Post-SPY). Baseline characteristics were similar between the groups. Both groups had high rates of comorbidities, chemotherapy, and radiation therapy. The rate of postoperative complications was two-fold higher in the Pre-SPY group compared to the Post-SPY group (36.5% vs. 17.9%); this difference was of borderline significance (P = 0.0631). However, mean number of repeat visits to the OR per patient was significantly higher in the Pre-SPY group (1.21 ± 1.47 vs. 0.41 ± 0.71; P = 0.0023). Of the seven patients with

  15. Evolution of pulmonary perfusion defects demonstrated with contrast-enhanced dynamic MR perfusion imaging.

    PubMed

    Howarth, N R; Beziat, C; Berthezène, Y

    1999-01-01

    Pulmonary perfusion defects can be demonstrated with contrast-enhanced dynamic MR perfusion imaging. We present the case of a patient with a pulmonary artery sarcoma who presented with a post-operative pulmonary embolus and was followed in the post-operative period with dynamic contrast-enhanced MR perfusion imaging. This technique allows rapid imaging of the first passage of contrast material through the lung after bolus injection in a peripheral vein. To our knowledge, this case report is the first to describe the use of this MR technique in showing the evolution of peripheral pulmonary perfusion defects associated with pulmonary emboli.

  16. Hyperoxia, but not thoracic X-irradiation, potentiates bleomycin- and cyclophosphamide-induced lung damage in mice

    SciTech Connect

    Hakkinen, P.J.; Whiteley, J.W.; Witschi, H.R.

    1982-08-01

    The intraperitoneal administration of cyclophosphamide or bleomycin to BALB/c mice resulted in lung cell damage followed by cellular proliferation, which was quantitated by measuring the increase in thymidine incorporation into pulmonary DNA. We have previously shown that administration of the antioxidant butylated hydroxytoluene produces lung damage that can be potentiated by both hyperoxia and thoracic X-irradiation. In the present study we show that hyperoxic exposure also potentiates bleomycin- and cyclophosphamide-induced acute lung damage. However, thoracic X-irradiation does not potentiate bleomycin- and cyclophosphamide-induced lung toxicity.

  17. Optimal pulmonary artery perfusion mode and perfusion pressure during cardiopulmonary bypass.

    PubMed

    Zhang, R; Wang, Z; Wang, H; Song, H; Zhang, N; Fang, M

    2010-06-01

    Reducing lung injury during cardiopulmonary bypass (CPB) is important for patients' recovery. The present study was designed to evaluate the effects of pulmonary artery perfusion pressure on the extent of lung injury during CPB in an animal model. Twenty healthy mongrel dogs were randomly divided into four groups, including a control group and three perfusion groups designed to simulate clinical cardiopulmonary bypass-induced lung injury. During pulmonary ischemia and cardiopulmonary bypass, protective perfusions were performed using different perfusion pressures (15-20, 25-30, and 40-45 mmHg), while animals in the control group were not perfused. After pulmonary reperfusion, the changes in pulmonary function and tissue histopathology were determined. Compared with the control group, lung compliance, oxygenation and vascular resistance after reperfusion were significantly improved in both low- and moderate-pressure groups. The malonaldehyde concentration, neutrophil sequestration ratio, and expression of ICAM-1 were also decreased significantly in the two groups. However, there were no significant differences in any of these parameters between the control group and the high-pressure group. Histopathological examination demonstrated that there were obvious inflammatory cell infiltration and tissue damage in the control and high-pressure groups, which was prevented in the low- and moderate-pressure groups. The perfusion pressure is an important factor that determines the extent of lung protection, and the use of pressures below 30 mmHg is optimal, with the safest and most effective range being 15-20 mmHg.

  18. Blinded Validation of Breath Biomarkers of Lung Cancer, a Potential Ancillary to Chest CT Screening

    PubMed Central

    Phillips, Michael; Bauer, Thomas L.; Cataneo, Renee N.; Lebauer, Cassie; Mundada, Mayur; Pass, Harvey I.; Ramakrishna, Naren; Rom, William N.; Vallières, Eric

    2015-01-01

    Background Breath volatile organic compounds (VOCs) have been reported as biomarkers of lung cancer, but it is not known if biomarkers identified in one group can identify disease in a separate independent cohort. Also, it is not known if combining breath biomarkers with chest CT has the potential to improve the sensitivity and specificity of lung cancer screening. Methods Model-building phase (unblinded): Breath VOCs were analyzed with gas chromatography mass spectrometry in 82 asymptomatic smokers having screening chest CT, 84 symptomatic high-risk subjects with a tissue diagnosis, 100 without a tissue diagnosis, and 35 healthy subjects. Multiple Monte Carlo simulations identified breath VOC mass ions with greater than random diagnostic accuracy for lung cancer, and these were combined in a multivariate predictive algorithm. Model-testing phase (blinded validation): We analyzed breath VOCs in an independent cohort of similar subjects (n = 70, 51, 75 and 19 respectively). The algorithm predicted discriminant function (DF) values in blinded replicate breath VOC samples analyzed independently at two laboratories (A and B). Outcome modeling: We modeled the expected effects of combining breath biomarkers with chest CT on the sensitivity and specificity of lung cancer screening. Results Unblinded model-building phase. The algorithm identified lung cancer with sensitivity 74.0%, specificity 70.7% and C-statistic 0.78. Blinded model-testing phase: The algorithm identified lung cancer at Laboratory A with sensitivity 68.0%, specificity 68.4%, C-statistic 0.71; and at Laboratory B with sensitivity 70.1%, specificity 68.0%, C-statistic 0.70, with linear correlation between replicates (r = 0.88). In a projected outcome model, breath biomarkers increased the sensitivity, specificity, and positive and negative predictive values of chest CT for lung cancer when the tests were combined in series or parallel. Conclusions Breath VOC mass ion biomarkers identified lung cancer in a

  19. Potential usefulness of an artificial neural network for differential diagnosis of interstitial lung diseases: pilot study.

    PubMed

    Asada, N; Doi, K; MacMahon, H; Montner, S M; Giger, M L; Abe, C; Wu, Y

    1990-12-01

    An artificial neural network approach was applied to the differential diagnosis of interstitial lung diseases. The neural network was designed to distinguish between nine types of interstitial lung diseases on the basis of 20 items of clinical and radiographic information. A data base for training and testing the neural network was created with 10 hypothetical cases for each of the nine diseases. The performance of the neural network was evaluated by means of receiver operating characteristic analysis. The decision performance of the neural network was high; it was comparable to that of chest radiologists and superior to that of senior radiology residents. The preliminary results strongly suggest that the neural network approach has potential utility in the computer-aided differential diagnosis of interstitial lung diseases.

  20. Redistribution of air within the lungs may potentiate "fright" bradycardia in submerged crocodiles (Crocodylus porosus).

    PubMed

    Wright, J C; Grigg, G C; Franklin, C E

    1992-05-01

    1. Voluntary undisturbed dives by Crocodylus porosus were short in duration (3.08 +/- 1.87 min, mean +/- SD) and accompanied by a small but significant bradycardia (14.3 +/- 5.9% drop). 2. When crocodiles were disturbed underwater there was a rapid onset of "fright" bradycardia, to 65 +/- 6.0% of surface heart rates and dive durations were prolonged to 19.6 +/- 1.8 min. 3. The development of "fright" bradycardia was not accompanied by any increase in intratracheal pressure or expulsion of lung gas. However, sustained contraction of the abdomen and expansion of the thorax revealed a redistribution of air anteriorly within the lungs. 4. We propose that the redistribution of air within the lungs may generate an afferent signal which potentiates the initiation of a severe, dive-prolonging bradycardia.

  1. Transposable elements and their potential role in complex lung disorder.

    PubMed

    Sargurupremraj, Muralidharan; Wjst, Matthias

    2013-10-05

    Transposable elements (TEs) are a class of mobile genetic elements (MGEs) that were long regarded as junk DNA, which make up approximately 45% of the genome. Although most of these elements are rendered inactive by mutations and other gene silencing mechanisms, TEs such as long interspersed nuclear elements (LINEs) are still active and translocate within the genome. During transposition, they may create lesions in the genome, thereby acting as epigenetic modifiers. Approximately 65 disease-causing LINE insertion events have been reported thus far; however, any possible role of TEs in complex disorders is not well established. Chronic obstructive pulmonary disease (COPD) is one such complex disease that is primarily caused by cigarette smoking. Although the exact molecular mechanism underlying COPD remains unclear, oxidative stress is thought to be the main factor in the pathogenesis of COPD. In this review, we explore the potential role of oxidative stress in epigenetic activation of TEs such as LINEs and the subsequent cascade of molecular damage. Recent advancements in sequencing and computation have eased the identification of mobile elements. Therefore, a comparative study on the activity of these elements and markers for genome instability would give more insight on the relationship between MGEs and complex disorder such as COPD.

  2. Repeat perfusion imaging may differentiate airways obstruction from pulomonary embolic disease: report of two cases

    SciTech Connect

    Greenspon, L.W.; LaManna, M.M.; Dhand, S.

    1987-06-01

    Two cases are presented in which patients with obstructive lung disease were considered to have a pulmonary embolism (PE). Emergency lung perfusion scans supported the diagnosis of PE in both cases. However, rapid resolution of the symptoms and perfusion defects by repeat ventilation-perfusion scanning at 24 hr suggested that PE was unlikely. In selected cases of wheezing patients, repeat perfusion scans may obviate the need for pulmonary angiography. The authors report two cases in which repeat perfusion scans almost normalized by 24 hr. Review of the literature indicates that the rate of resolution of perfusion defects would have been much slower had pulmonary embolism occurred.

  3. Oral Cell DNA Adducts as Potential Biomarkers for Lung Cancer Susceptibility in Cigarette Smokers

    PubMed Central

    Hecht, Stephen S.

    2017-01-01

    This perspective considers the use of oral cell DNA adducts, together with exposure and genetic information, to potentially identify those cigarette smokers at highest risk for lung cancer, so that appropriate preventive measures could be initiated at a relatively young age before too much damage has been done. There are now well established and validated analytical methods for the quantitation of urinary and serum metabolites of tobacco smoke toxicants and carcinogens. These metabolites provide a profile of exposure and in some cases lung cancer risk. But they do not yield information on the critical DNA damage parameter that leads to mutations in cancer growth control genes such as KRAS and TP53. Studies demonstrate a correlation between changes in the oral cavity and lung in cigarette smokers, due to the field effect of tobacco smoke. Oral cell DNA is readily obtained in contrast to DNA samples from the lung. Studies in which oral cell DNA and salivary DNA have been analyzed for specific DNA adducts are reviewed; some of the adducts identified have also been previously reported in lung DNA from smokers. The multiple challenges of developing a panel of oral cell DNA adducts that could be routinely quantified by mass spectrometry are discussed. PMID:28092948

  4. The down-regulated ING5 expression in lung cancer: A potential target of gene therapy

    PubMed Central

    Zhao, Shuang; Yang, Xue-feng; Shen, Dao-fu; Gao, Yang; Shi, Shuai; Wu, Ji-cheng; Liu, Hong-xu; Sun, Hong-zhi; Su, Rong-jian; Zheng, Hua-chuan

    2016-01-01

    ING5 can interact with p53, thereby inhibiting cell growth and inducing apoptosis. We found that ING5 overexpression not only inhibited proliferation, migration, and invasion, but also induced G2 arrest, differentiation, autophagy, apoptosis, glycolysis and mitochondrial respiration in lung cancer cells. ING5 transfection up-regulated the expression of Cdc2, ATG13, ATG14, Beclin-1, LC-3B, AIF, cytochrome c, Akt1/2/3, ADFP, PFK-1 and PDPc, while down-regulated the expression of Bcl-2, XIAP, survivin,β-catenin and HXK1. ING5 transfection desensitized cells to the chemotherapy of MG132, paclitaxel, and SAHA, which paralleled with apoptotic alteration. ING5 overexpression suppressed the xenograft tumor growth by inhibiting proliferation and inducing apoptosis. ING5 expression level was significantly higher in normal tissue than that in lung cancer at both protein and mRNA levels. Nuclear ING5 expression was positively correlated with ki-67 expression and cytoplasmic ING5 expression. Cytoplasmic ING5 expression was positively associated with lymph node metastasis, and negatively with age, lymphatic invasion or CPP32 expression. ING5 expression was different in histological classification: squamous cell carcinoma > adenocarcinoma > large cell carcinoma > small cell carcinoma. Taken together, our data suggested that ING5 downregulation might involved in carcinogenesis, growth, and invasion of lung cancer and could be considered as a promising marker to gauge the aggressiveness of lung cancer. It might be employed as a potential target for gene therapy of lung cancer. PMID:27409347

  5. Oral Cell DNA Adducts as Potential Biomarkers for Lung Cancer Susceptibility in Cigarette Smokers.

    PubMed

    Hecht, Stephen S

    2017-01-17

    This perspective considers the use of oral cell DNA adducts, together with exposure and genetic information, to potentially identify those cigarette smokers at highest risk for lung cancer, so that appropriate preventive measures could be initiated at a relatively young age before too much damage has been done. There are now well established and validated analytical methods for the quantitation of urinary and serum metabolites of tobacco smoke toxicants and carcinogens. These metabolites provide a profile of exposure and in some cases lung cancer risk, but they do not yield information on the critical DNA damage parameter that leads to mutations in cancer growth control genes such as KRAS and TP53. Studies demonstrate a correlation between changes in the oral cavity and lung in cigarette smokers, due to the field effect of tobacco smoke. Oral cell DNA is readily obtained in contrast to DNA samples from the lung. Studies in which oral cell DNA and salivary DNA have been analyzed for specific DNA adducts are reviewed; some of the adducts identified have also been previously reported in lung DNA from smokers. The multiple challenges of developing a panel of oral cell DNA adducts that could be routinely quantified by mass spectrometry are discussed.

  6. Investigation of the potential carcinogenicity of a range of chromium containing materials on rat lung.

    PubMed Central

    Levy, L S; Martin, P A; Bidstrup, P L

    1986-01-01

    Twenty one chromium containing materials were examined for carcinogenic activity in a two year study using an intrabronchial pellet implantation system whereby pellets loaded with test material were surgically implanted into the lower left bronchus of rats. The principal aim of the study was to extend our knowledge of the carcinogenic potential of chromium compounds and, in particular, chromates (Cr6+). A statistically significant incidence of treatment related lung tumours was found with some sparingly soluble chromate materials. All tumours were large keratinizing squamous carcinomas of the left lung, except for a single left lung adenocarcinoma and two left lung anaplastic carcinomas. No bronchial carcinomas (0/100) were seen in the negative control group (blank pellet loaded with cholesterol), whereas bronchial carcinomas (22/48 and 25/100) occurred in the two positive control groups which received pellets loaded with 20-methylcholanthrene and calcium chromate respectively. Among the 20 test materials, only three groups gave statistically significant numbers of bronchial carcinomas. Two of these were groups receiving different samples of strontium chromate which gave 43/99 and 62/99 tumours. The third group, zinc chromate (low solubility), gave 5/100 bronchial carcinomas. A further zinc chromate group (Norge composition) produced 3/100 bronchial carcinomas which was not statistically significant. A few lung tumours were observed in other test groups. Images PMID:3964573

  7. Medicinal Plants and Other Living Organisms with Antitumor Potential against Lung Cancer

    PubMed Central

    Monteiro, Luara de Sousa; Bastos, Katherine Xavier; Barbosa-Filho, José Maria; de Athayde-Filho, Petrônio Filgueiras; Diniz, Margareth de Fátima Formiga Melo; Sobral, Marianna Vieira

    2014-01-01

    Lung cancer is a disease with high morbidity and mortality rates. As a result, it is often associated with a significant amount of suffering and a general decrease in the quality of life. Herbal medicines are recognized as an attractive approach to lung cancer therapy with little side effects and are a major source of new drugs. The aim of this work was to review the medicinal plants and other living organisms with antitumor potential against lung cancer. The assays were conducted with animals and humans, and Lewis lung carcinoma was the most used experimental model. China, Japan, South Korea, and Ethiopia were the countries that most published studies of species with antitumor activity. Of the 38 plants evaluated, 27 demonstrated antitumor activity. In addition, six other living organisms were cited for antitumor activity against lung cancer. Mechanisms of action, combination with chemotherapeutic drugs, and new technologies to increase activity and reduce the toxicity of the treatment are discussed. This review was based on the NAPRALERT databank, Web of Science, and Chemical Abstracts. This work shows that natural products from plants continue to be a rich source of herbal medicines or biologically active compounds against cancer. PMID:25147575

  8. The Effect of the Prosthetic Group on the Pharmacologic Properties of 18F-labeled Rhodamine B, a Potential Myocardial Perfusion Agent for PET

    PubMed Central

    Bartholomä, Mark D.; Gottumukkala, Vijay; Zhang, Shaohui; Baker, Amanda; Dunning, Patricia; Fahey, Frederic H.; Treves, S. Ted; Packard, Alan B.

    2013-01-01

    We recently reported the development of the 2-[18F]fluoroethyl ester of rhodamine B as a potential positron emission tomography (PET) tracer for myocardial perfusion imaging. This compound, which was prepared using a [18F]fluoroethyl prosthetic group, has significant uptake in the myocardium in rats, but also demonstrates relatively high liver uptake and is rapidly hydrolyzed in vivo in mice. We have now prepared 18F-labeled rhodamine B using three additional prosthetic groups (propyl, diethylene glycol, and triethylene glycol) and found that the prosthetic group has a significant effect on the in vitro and in vivo properties of these compounds. Of the esters prepared to date, the diethylene glycol ester is superior in terms of in vitro stability and pharmacokinetics. These observations suggest that the prosthetic group plays a significant role in determining the pharmacological properties of 18F-labeled compounds. They also support the value of continued investigation of 18F-labeled rhodamines as PET radiopharmaceuticals for myocardial perfusion imaging. PMID:23210516

  9. Pulmonary ventilation and perfusion abnormalities and ventilation perfusion imbalance in children with pulmonary atresia or extreme tetralogy of Fallot

    SciTech Connect

    Dowdle, S.C.; Human, D.G.; Mann, M.D. )

    1990-08-01

    Xenon-133 lung ventilation and perfusion scans were done preoperatively after cardiac catheterization and cineangiocardiography in 19 children; 6 had pulmonary atresia with an intact ventricular septum and hypoplastic right ventricle, 4 pulmonary atresia with associated complex univentricular heart, and 9 extreme Tetralogy of Fallot. The four patients with discrepancies in the sizes of the left and right pulmonary arteries on angiography had marked asymmetry of pulmonary perfusion and ventilation-perfusion imbalance on scintigraphy. Similar degrees of asymmetry and imbalance were present in 6 of the 15 children with equal-size pulmonary vessels. Asymmetry of pulmonary perfusion and ventilation-perfusion imbalance were associated with a poor prognosis.

  10. Ventilation-perfusion imaging in pulmonary papillomatosis.

    PubMed

    Espinola, D; Rupani, H; Camargo, E E; Wagner, H N

    1981-11-01

    Three children with laryngeal papillomas involving the lungs had serial ventilation-perfusion scintigrams to assess results of therapy designed to reduce the bronchial involvement. Different imaging patterns were observed depending on size, number, and location of lesions. In early parenchymal involvement a ventilation-perfusion mismatch was seen. The initial and follow-up studies correlated well with clinical and radiographic findings. This noninvasive procedure is helpful in evaluating ventilatory and perfusion impairment in these patients as well as their response to treatment.

  11. Ventilation-perfusion imaging in pulmonary papillomatosis

    SciTech Connect

    Espinola, D.; Rupani, H.; Camargo, E.E.; Wagner, H.N. Jr.

    1981-11-01

    Three children with laryngeal papillomas involving the lungs had serial ventilation-perfusion scintigrams to assess results of therapy designed to reduce the bronchial involvement. Different imaging patterns were observed depending on size, number, and location of lesions. In early parenchymal involvement a ventilation-perfusion mismatch was seen. The initial and follow-up studies correlated well with clinical and radiographic findings. This noninvasive procedure is helpful in evaluating ventilatory and perfusion impairment in these patients as well as their response to treatment.

  12. Lung Microtissue Array to Screen the Fibrogenic Potential of Carbon Nanotubes

    PubMed Central

    Chen, Zhaowei; Wang, Qixin; Asmani, Mohammadnabi; Li, Yan; Liu, Chang; Li, Changning; Lippmann, Julian M.; Wu, Yun; Zhao, Ruogang

    2016-01-01

    Due to their excellent physical and chemical characteristics, multi-wall carbon nanotubes (MWCNT) have the potential to be used in structural composites, conductive materials, sensors, drug delivery and medical imaging. However, because of their small-size and light-weight, the applications of MWCNT also raise health concerns. In vivo animal studies have shown that MWCNT cause biomechanical and genetic alterations in the lung tissue which lead to lung fibrosis. To screen the fibrogenic risk factor of specific types of MWCNT, we developed a human lung microtissue array device that allows real-time and in-situ readout of the biomechanical properties of the engineered lung microtissue upon MWCNT insult. We showed that the higher the MWCNT concentration, the more severe cytotoxicity was observed. More importantly, short type MWCNT at low concentration of 50 ng/ml stimulated microtissue formation and contraction force generation, and caused substantial increase in the fibrogenic marker miR-21 expression, indicating the high fibrogenic potential of this specific carbon nanotube type and concentration. The presented microtissue array system provides a powerful tool for high-throughput examination of the therapeutic and toxicological effects of target compounds in realistic tissue environment. PMID:27510174

  13. Expression Profiling Identifies Bezafibrate as Potential Therapeutic Drug for Lung Adenocarcinoma

    PubMed Central

    Liu, Xinyan; Yang, Xiaoqin; Chen, Xinmei; Zhang, Yantao; Pan, Xuebin; Wang, Guiping; Ye, Yun

    2015-01-01

    Drug-induced gene expression patterns that invert disease profiles have recently been illustrated to be a new strategy for drug-repositioning. In the present study, we validated this approach and focused on prediction of novel drugs for lung adenocarcinoma (AC), for which there is a pressing need to find novel therapeutic compounds. Firstly, connectivity map (CMap) analysis computationally predicted bezafibrate as a putative compound against lung AC. Then this hypothesis was verified by in vitro assays of anti-proliferation and cell cycle arrest. In silico docking evidence indicated that bezafibrate could target cyclin dependent kinase 2(CDK2), which regulates progression through the cell cycle. Furthermore, we found that bezafibrate can significantly down-regulate the expression of CDK2 mRNA and p-CDK2. Using a nude mice xenograft model, we also found that bezafibrate could inhibit tumor growth of lung AC in vivo. In conclusion, this study proposed bezafibrate as a potential therapeutic option for lung AC patients, illustrating the potential of in silico drug screening. PMID:26535062

  14. Lung Biopersistence and in Vitro Dissolution Rate Predict the Pathogenic Potential of Synthetic Vitreous Fibers.

    PubMed

    Hesterberg, T W; Hart, G A

    2000-01-01

    . Other in vitro studies of fiber degradation suggest that, in addition to fiber dissolution, fiber leaching and subsequent transverse breakage may also be important mechanisms in lung biopersistence and hence pathogenicity. The validity of using lung biopersistence for predicting the potential pathogenicity of SVFs is confirmed by this research. The research also supports the use of in vitro fiber degradation at pH 7.4 and/or pH 4.5 as an indicator of SVF potential pathogenicity.

  15. Time-resolved three-dimensional pulmonary MR angiography and perfusion imaging with ultrashort repetition time.

    PubMed

    Carr, James C; Laub, Gerhard; Zheng, Jie; Pereles, F Scott; Finn, J Paul

    2002-12-01

    The purpose of this study was to implement ultrafast, multiphase three-dimensional (3D) magnetic resonance (MR) angiography and perfusion imaging after bolus injection of contrast medium to generate preliminary validation of parameters in a pig model and to illustrate potential applications in patients with lung abnormalities. Five healthy volunteers, five patients, and three pigs underwent rapid, time-resolved pulmonary MR angiography and perfusion imaging on a 1.5-T MR imager. All patients had undergone correlative computed tomographic or conventional angiography. The pulse sequence was a 3D spin-warp, gradient-echo acquisition with a repetition time of 1.6 msec and an echo time of 0.6 msec. Each 3D acquisition lasted 2-3 seconds, and 8-16 sequential measurements were made in each study. Artificial pulmonary emboli were generated in pigs with gelatin sponge. All patients had diseases of the pulmonary circulation (as confirmed with other studies). Multiphasic, time-resolved pulmonary parenchymal enhancement was demonstrated in all healthy subjects and animals. All segmental (n = 100) and subsegmental (n = 200) branches were identified in the healthy subjects. Perfusion deficits were clearly demonstrated in all pigs after gelatin embolization. Perfusion defects were identified in two patients with lung disease. Abnormalities of the pulmonary vasculature were clearly identified in the patient group. Dynamic time-resolved 3D pulmonary MR angiography and perfusion imaging is feasible in humans as well as in animals. Induced perfusion deficits are identifiable after artificial embolization in pigs. Combined pulmonary MR angiography and parenchymal (perfusion) imaging may improve evaluation of the pulmonary circulation in a variety of conditions.

  16. Therapeutic Potential of Denosumab in Patients With Lung Cancer: Beyond Prevention of Skeletal Complications.

    PubMed

    De Castro, Javier; García, Rosario; Garrido, Pilar; Isla, Dolores; Massuti, Bartomeu; Blanca, Belén; Vázquez, Jimena

    2015-11-01

    Approximately up to 40% of patients with lung cancer develop bone metastasis, with 22% to 59% of them experiencing skeletal-related events (SREs), which result in an important quality of life deterioration and economic burden. Denosumab, a fully human antibody that targets the receptor activator of nuclear factor-κB (RANK) ligand (RANKL), is indicated for prevention of SREs in patients with solid tumors and has demonstrated superiority in breast and prostate cancer, and in other solid tumors, in reducing the risk of first SRE by 17% versus zoledronic acid. In the subset of patients with non-small-cell lung carcinoma (NSCLC), denosumab has also shown a positive trend to SRE risk reduction. Denosumab might have direct or indirect antitumor effects. Cancer cells produce factors that stimulate increased bone resorption by osteoclasts, which in turn release tumor growth factors into the bone microenvironment, initiating a tumor/bone vicious cycle. An increasing body of evidence suggests RANK/RANKL signaling plays a role in this tumorigenesis. Both proteins are overexpressed in different tumor types including lung cancer cells. RANK/RANKL signaling activates nuclear factor-κB pathways related to lung carcinogenesis and increases intercellular adhesion molecule 1 expression and MEK/extracellular signal-regulated kinase phosphorylation, which in turn enhances tumor cell migration. In animal NSCLC models, denosumab delayed bone metastases and reduced skeletal tumor growth. In patients with lung cancer (post hoc analysis), denosumab prolonged overall survival by 1.2 months versus zoledronic acid (P = .01). This hypothesis-generating outcome warrants further investigation and 2 studies in lung cancer are ongoing to elucidate the therapeutic potential of denosumab beyond SRE prevention.

  17. The fibrogenic actions of lung fibroblast-derived urokinase: a potential drug target in IPF

    PubMed Central

    Schuliga, Michael; Jaffar, Jade; Harris, Trudi; Knight, Darryl A; Westall, Glen; Stewart, Alastair G

    2017-01-01

    The role of urokinase plasminogen activator (uPA) in idiopathic pulmonary fibrosis (IPF) remains unclear. uPA-generated plasmin has potent fibrogenic actions involving protease activated receptor-1 (PAR-1) and interleukin-6 (IL-6). Here we characterize uPA distribution or levels in lung tissue and sera from IPF patients to establish the mechanism of its fibrogenic actions on lung fibroblasts (LFs). uPA immunoreactivity was detected in regions of fibrosis including fibroblasts of lung tissue from IPF patients (n = 7). Serum uPA levels and activity were also higher in IPF patients (n = 18) than controls (n = 18) (P < 0.05), being negatively correlated with lung function as measured by forced vital capacity (FVC) %predicted (P < 0.05). The culture supernatants of LFs from IPF patients, as compared to controls, showed an increase in plasmin activity after plasminogen incubation (5–15 μg/mL), corresponding with increased levels of uPA and IL-6 (n = 5–6, P < 0.05). Plasminogen-induced increases in plasmin activity and IL-6 levels were attenuated by reducing uPA and/or PAR-1 expression by RNAi. Plasmin(ogen)-induced mitogenesis was also attenuated by targeting uPA, PAR-1 or IL-6. Our data shows uPA is formed in active regions of fibrosis in IPF lung and contributes to LF plasmin generation, IL-6 production and proliferation. Urokinase is a potential target for the treatment of lung fibrosis. PMID:28139758

  18. An understanding of potential and limitations of alginate/PLL microcapsules as a cell retention system for perfusion cultures.

    PubMed

    Demont, Aurelie; Cole, Harriet; Marison, Ian W

    2016-02-01

    Microcapsules for high cell density culture of mammalian cells have found an increasing interest, however, the poor stability of the microcapsules and the lack of characterisation methods led to few quantitative results. Alginate-poly-L-lysine (PLL) microcapsules have been studied in detail in order to form a basis for comparison of capsules made from different polymers. Since the microcapsules can be easily retained in the bioreactor without the need for a cell separation device, high cell densities were achieved with a maximum of 4 × 10(7) cell/ml(microcapsules), corresponding to a colonisation of 5% of the internal capsule volume. Measurement of microcapsule integrity and mechanical resistance showed that alginate-PLL microcapsules are not suitable for perfusion cultures since they are very sensitive to media composition, mainly the presence of non-gelling ions that have a higher affinity for alginate than PLL and Ca(2+), leading to the leakage of PLL and Ca(2+), and to microcapsule rupture.

  19. Anthocyanins block ischemia-induced apoptosis in the perfused heart and support mitochondrial respiration potentially by reducing cytosolic cytochrome c.

    PubMed

    Skemiene, Kristina; Rakauskaite, Gintare; Trumbeckaite, Sonata; Liobikas, Julius; Brown, Guy C; Borutaite, Vilmante

    2013-01-01

    Anthocynanins, found in fruits and vegetables, have a variety of protective properties, which have generally been attributed to their antioxidant capacity. However, antioxidants are generally strong reductants, and some reductants have been found to block apoptosis by reducing cytosolic cytochrome c, which prevents caspase activation. We tested the ability of various anthocyanins: to reduce cytochrome c, to support cytochrome c-induced mitochondrial respiration and to inhibit apoptosis induced by heart ischemia. Anthocyanins such as delphinidin-3-glucoside (Dp3G) and cyanidin-3-glucoside (Cy3G) were able to reduce cytochrome c directly and rapidly, whereas pelargonidin-3-glucoside (Pg3G), malvinidin-3-glucoside (Mv3G) and peonidin-3-glucoside (Pn3G) had relatively low cytochrome c reducing activities. Dp3G and Cy3G but not Pg3G supported mitochondrial state 4 respiration in the presence of exogenous cytochrome c. Pre-perfusion of hearts with 20 μM Cy3G but not Pg3G prevented ischemia-induced caspase activation. This suggests that the ability of anthocyanins to block caspase activation may be due to their ability to reduce cytosolic cytochrome c. This article is part of a Directed Issue entitled: Bioenergetic dysfunction, adaptation and therapy. Copyright © 2012 Elsevier Ltd. All rights reserved.

  20. MR pulmonary angiography and perfusion imaging: recent advances.

    PubMed

    Hatabu, H

    1997-10-01

    Recent advances in MR pulmonary angiography and MR perfusion imaging are reviewed, focusing on two principal areas of technical development: (1) the availability of MR scanners equipped with enhanced gradient systems; and (2) new trends in MR angiography using gadolinium contrast agents or labeling of blood with an inversion recovery radiofrequency pulse in place of the more traditional methods using naturally flowing spins as the source of intravascular signal. These recent developments in MR have significant potential for clinical imaging of the pulmonary vasculature, particularly for the diagnosis of pulmonary embolism, and are now opening windows to functional MR imaging of the lung.

  1. Hyaluronic acid-modified zirconium phosphate nanoparticles for potential lung cancer therapy.

    PubMed

    Li, Ranwei; Liu, Tiecheng; Wang, Ke

    2017-02-01

    Novel tumor-targeting zirconium phosphate (ZP) nanoparticles modified with hyaluronic acid (HA) were developed (HA-ZP), with the aim of combining the drug-loading property of ZP and the tumor-targeting ability of HA to construct a tumor-targeting paclitaxel (PTX) delivery system for potential lung cancer therapy. The experimental results indicated that PTX loading into the HA-ZP nanoparticles was as high as 20.36%±4.37%, which is favorable for cancer therapy. PTX-loaded HA-ZP nanoparticles increased the accumulation of PTX in A549 lung cancer cells via HA-mediated endocytosis and exhibited superior anticancer activity in vitro. In vivo anticancer efficacy assay revealed that HA-ZP nanoparticles possessed preferable anticancer abilities, which exhibited minimized toxic side effects of PTX and strong tumor-suppression potential in clinical application.

  2. Plasma secretory phospholipase A2-IIa as a potential biomarker for lung cancer in patients with solitary pulmonary nodules

    PubMed Central

    2011-01-01

    Background Five-year survival for lung cancer has remained at 16% over last several decades largely due to the fact that over 50% of patients are diagnosed with locally-advanced or metastatic disease. Diagnosis at an earlier and potentially curable stage is crucial. Solitary pulmonary nodules (SPNs) are common, but the difficulty lies in the determination of which SPN is malignant. Currently, there is no convenient and reliable biomarker effective for early diagnosis. Secretory phospholipase A2-IIa (sPLA2-IIa) is secreted into the circulation by cancer cells and may allow for an early detection of lung cancer. Methods Plasma samples from healthy donors, patients with only benign SPN, and patients with lung cancer were analyzed. Expression of sPLA2-IIa protein in lung cancer tissues was also determined. Results We found that the levels of plasma sPLA2-IIa were significantly elevated in lung cancer patients. The receiver operating characteristic curve analysis, comparing lung cancer patients to patients with benign nodules, revealed an optimum cutoff value for plasma sPLA2-IIa of 2.4 ng/ml to predict an early stage cancer with 48% sensitivity and 86% specificity and up to 67% sensitivity for T2 stage lung cancer. Combined sPLA2-IIa, CEA, and Cyfra21.1 tests increased the sensitivity for lung cancer prediction. High level of plasma sPLA2-IIa was associated with a decreased overall cancer survival. sPLA2-IIa was overexpressed in almost all non-small cell lung cancer and in the majority of small cell lung cancer by immunohistochemistry analysis. Conclusion Our finding strongly suggests that plasma sPLA2-IIa is a potential lung biomarker to distinguish benign nodules from lung cancer and to aid lung cancer diagnosis in patients with SPNs. PMID:22151235

  3. Molecular and Cellular Effects of Hydrogen Peroxide on Human Lung Cancer Cells: Potential Therapeutic Implications

    PubMed Central

    2016-01-01

    Lung cancer has a very high mortality-to-incidence ratio, representing one of the main causes of cancer mortality worldwide. Therefore, new treatment strategies are urgently needed. Several diseases including lung cancer have been associated with the action of reactive oxygen species (ROS) from which hydrogen peroxide (H2O2) is one of the most studied. Despite the fact that H2O2 may have opposite effects on cell proliferation depending on the concentration and cell type, it triggers several antiproliferative responses. H2O2 produces both nuclear and mitochondrial DNA lesions, increases the expression of cell adhesion molecules, and increases p53 activity and other transcription factors orchestrating cancer cell death. In addition, H2O2 facilitates the endocytosis of oligonucleotides, affects membrane proteins, induces calcium release, and decreases cancer cell migration and invasion. Furthermore, the MAPK pathway and the expression of genes related to inflammation including interleukins, TNF-α, and NF-κB are also affected by H2O2. Herein, we will summarize the main effects of hydrogen peroxide on human lung cancer leading to suggesting it as a potential therapeutic tool to fight this disease. Because of the multimechanistic nature of this molecule, novel therapeutic approaches for lung cancer based on the use of H2O2 may help to decrease the mortality from this malignancy. PMID:27375834

  4. The roles of miRNAs as potential biomarkers in lung diseases.

    PubMed

    Alipoor, Shamila D; Adcock, Ian M; Garssen, Johan; Mortaz, Esmaeil; Varahram, Mohammad; Mirsaeidi, Mehdi; Velayati, Aliakbar

    2016-11-15

    MicroRNAs (miRNAs) are small non-coding RNAs which can act as master regulators of gene expression, modulate almost all biological process and are essential for maintaining cellular homeostasis. Dysregulation of miRNA expression has been associated with aberrant gene expression and may lead to pathological conditions. Evidence suggests that miRNA expression profiles are altered between health and disease and as such may be considered as biomarkers of disease. Evidence is increasing that miRNAs are particularly important in lung homeostasis and development and have been demonstrated to be the involved in many pulmonary diseases such as asthma, COPD, sarcoidosis, lung cancer and other smoking related diseases. Better understanding of the function of miRNA and the mechanisms underlying their action in the lung, would help to improve current diagnosis and therapeutics strategies in pulmonary diseases. Recently, some miRNA-based drugs have been introduced as possible therapeutic agents. In this review we aim to summarize the recent findings regarding the role of miRNAs in the airways and lung and emphasise their potential therapeutic roles in pulmonary diseases.

  5. Identification of metabolomics panels for potential lung cancer screening by analysis of exhaled breath condensate.

    PubMed

    Peralbo-Molina, A; Calderón-Santiago, M; Priego-Capote, F; Jurado-Gámez, B; Luque de Castro, M D

    2016-03-23

    Exhaled breath condensate (EBC) is one of the less employed biofluids when searching for clinical markers, despite its non-invasive sampling and the potential relationship between its composition and respiratory disease phenotypes such as lung cancer. The advanced stage at which lung cancer is usually detected is the main reason for the high mortality rate of this carcinogenic disease. In this preliminary research, EBC was used as clinical sample to develop a screening tool for lung cancer discrimination from two control groups (with and without risk factor). Three panels of metabolites were configured using the PanelomiX tool to minimize false negatives (specificity) and false positives (sensitivity). The combination of five metabolites led to three panels providing a sensitivity above 77.9%, specificity above 67.5% and the area under the curve (AUC) above 77.5% for the three panels. An additional study was developed as a first approach to study the statistical significance of metabolites at different stages of lung cancer.

  6. Elastin metabolism and chemistry: potential roles in lung development and structure.

    PubMed Central

    Rucker, R B; Dubick, M A

    1984-01-01

    Elastic fibers are important for elasticity and extensibility of lung tissue. In the developing lung, elastic fibers appear in greatest numbers during the process or period of alveolarization . A variety of mesenchymal cells in lung appear responsible for elastin synthesis. Elastin is a novel protein both from the standpoint of its processing into elastic fibers and chemical properties. For example, elastin undergoes posttranslational modification before its assembly into fibers. These steps include limited proteolysis, hydroxylation of prolyl residues and the oxidative deamination of lysyl residues prior to their incorporation into the crosslinks that covalently bond together polypeptide chains of elastin. The crosslinking amino acids include lysinonorleucine , merodesmosine and desmosine isomers. A key enzyme that controls this process is lysyl oxidase. Lysyl oxidase is a copper metalloprotein whose activity is responsive to and modulated by environmental insults, nutrition deficiencies and the administration of various pharmacological agents. Regarding chemical properties, elastin is one of the most apolar proteins secreted by mammalian cells. Moreover, elastin is one of the most long-lived proteins secreted into the extracellular matrix. In relationship to its processing into elastic fibers and chemical properties, details related to major aspects of elastin metabolism as well as speculation on its potential as a factor in lung development and disease are discussed. Images FIGURE 1. PMID:6376098

  7. Air purifiers that diffuse reactive oxygen species potentially cause DNA damage in the lung.

    PubMed

    Kawamoto, Kosuke; Sato, Itaru; Yoshida, Midori; Tsuda, Shuji

    2010-12-01

    Several appliance manufacturers have recently released new type air purifiers that can disinfect bacteria, fungi and viruses by diffusing reactive oxygen species (ROS) into the air. In this study, mice were exposed to the outlet air from each of 3 air purifiers from different manufacturers (A, B, C), and the lung was examined for DNA damage, lipid peroxidation and histopathology to confirm the safety of these air purifiers. Neither abnormal behavior during exposure nor gross abnormality at necropsy was observed. No histopathological changes were also observed in the lung. However, significant increase of DNA damage was detected by the comet assay in the lung immediately after the direct exposure for 48 hr to models A and B, and for 16 hr to model B. As for model B, DNA migration was also increased by 2 hr exposure in a 1 m(3) plastic chamber but not by 48 hr exposure in a room (12.6 m(3)). Model C did not cause DNA damage. Lipid peroxidation and 8-hydroxy deoxyguanosine (8-OH-dG) was not increased under the conditions DNA damage was detected by the comet assay. The present results revealed that some models of air purifiers that diffuse ROS potentially cause DNA damage in the lung although the mechanism was left unsolved.

  8. Identification and validation of SAA as a potential lung cancer biomarker and its involvement in metastatic pathogenesis of lung cancer.

    PubMed

    Sung, Hye-Jin; Ahn, Jung-Mo; Yoon, Yeon-Hee; Rhim, Tai-Youn; Park, Choon-Sik; Park, Jae-Yong; Lee, Soo-Youn; Kim, Jong-Won; Cho, Je-Yoel

    2011-03-04

    Lung cancer is recently regarded as an overhealed inflammatory disease. Serum amyloid A (SAA) is known as an acute phase protein, but it is likely involved in the cancer pathogenesis. We identified both SAA1 and SAA2 in the pooled sera of lung cancer patients but not in the healthy control, by LC-MS/MS analysis. We found that about 14-fold higher levels of SAA in lung cancer patients' sera and plasma compared to healthy controls by ELISA using total 350 samples (13.89 ± 37.18 vs 190.49 ± 234.70 ug/mL). The SAA levels were also significantly higher than in other pulmonary disease or other cancers. An immunohistochemical study using tissue microarray showed that, unlike other cancer tissues, lung cancer tissues highly express SAA. Further in vitro experiments showed that SAA is induced from lung cancer cells by the interaction with THP-1 monocytes and this, in return, induces MMP-9 from THP-1. In in vivo animal models, overexpressed SAA promoted Lewis lung carcinoma (LLC) cells to metastasize and colonize in the lung. Our data suggest that a higher concentration of SAA can serve as an indicator of lung adenocarcinoma and represents a therapeutic target for the inhibition of lung cancer metastasis.

  9. Simultaneous measurements of magnesium, calcium and sodium influxes in perfused squid giant axons under membrane potential control.

    PubMed

    Rojas, E; Taylor, R E

    1975-10-01

    1. Giant axons from the squids Dosidicus gigas, Loligo forbesi and Loligo vulgaris were internally perfused with 550 or 275 mM KF plus sucrose and bathed in artificial sea water containing 45Ca, 28Mg or mixtures of 45Ca-28Mg or 45Ca-22Na. Resting influxes and extra influxes during voltage-clamp pulses were measured by collecting and counting the internal perfusate. 2. For Dosidicus axons in 10 mM-CaCl2 the resting influx of calcium was 0-016 +/- 0-007 p-mole/cm2 sec and a linear function of external concentration. For two experiments in 10 and 84-7 mM-CaCl2, 100 nM tetrodotoxin had no effect. Resting calcium influx in 10 mM-CaCl2 was 0-017 +/- 0-013 p-mole/cm2 sec for Loligo axons. 3. With 55 mM-MgCl2 outside the average resting magnesium influx was 0-124 +/- 0-080 p-mole/cm2 sec for Loligo axons. Discarding one aberrant point the value is 0-105 +/- 0-046 which is not significantly different from the resting calcium influx for Dosidicus fibres in 55 mM-CaCl2, given as 0-094 p-mole/cm2 sec by the regression line shown in Fig. 1. In two experiments 150 nM tetrodotoxin had no effect. 4. With 430 mM-NaCl outside 100 nM tetrodotoxin reduced the average resting influx of sodium in Dosidicus axon from 27-7 +/- 4-5 to 25-1 +/- 6-2 p-mole/cm2 sec and for Loligo fibres in 460 mM-NaCl from 50-5 +/- 4 to 20 +/- 8 p-mole/cm2 sec. 5. Using depolarizing pulses of various durations, the extra calcium influx occurred in two phases. The early phase was eliminated by external application of tetrodotoxin. The results of analysis are consistent with, but do not rigorously demonstrate, the conclusion that the tetrodotoxin sensitive calcium entry is flowing through the normal sodium channels (cf. Baker, Hodgkin & Ridgway, 1971). 6. Measurements of extra influxes using 22Na and 45Ca simultaneously indicate that the time courses of tetrodotoxin sensitive calcium and sodium entry are similar but not necessarily identical. It is very doubtful that any significant calcium entry occurs before

  10. Administration of hydrogen sulfide via extracorporeal membrane lung ventilation in sheep with partial cardiopulmonary bypass perfusion: a proof of concept study on metabolic and vasomotor effects

    PubMed Central

    2011-01-01

    Introduction Although inhalation of 80 parts per million (ppm) of hydrogen sulfide (H2S) reduces metabolism in mice, doses higher than 200 ppm of H2S were required to depress metabolism in rats. We therefore hypothesized that higher concentrations of H2S are required to reduce metabolism in larger mammals and humans. To avoid the potential pulmonary toxicity of H2S inhalation at high concentrations, we investigated whether administering H2S via ventilation of an extracorporeal membrane lung (ECML) would provide means to manipulate the metabolic rate in sheep. Methods A partial venoarterial cardiopulmonary bypass was established in anesthetized, ventilated (fraction of inspired oxygen = 0.5) sheep. The ECML was alternately ventilated with air or air containing 100, 200, or 300 ppm H2S for intervals of 1 hour. Metabolic rate was estimated on the basis of total CO2 production (V˙CO2) and O2 consumption (V˙O2). Continuous hemodynamic monitoring was performed via indwelling femoral and pulmonary artery catheters. Results V˙CO2, V˙O2, and cardiac output ranged within normal physiological limits when the ECML was ventilated with air and did not change after administration of up to 300 ppm H2S. Administration of 100, 200 and 300 ppm H2S increased pulmonary vascular resistance by 46, 52 and 141 dyn·s/cm5, respectively (all P ≤ 0.05 for air vs. 100, 200 and 300 ppm H2S, respectively), and mean pulmonary artery pressure by 4 mmHg (P ≤ 0.05), 3 mmHg (n.s.) and 11 mmHg (P ≤ 0.05), respectively, without changing pulmonary capillary wedge pressure or cardiac output. Exposure to 300 ppm H2S decreased systemic vascular resistance from 1,561 ± 553 to 870 ± 138 dyn·s/cm5 (P ≤ 0.05) and mean arterial pressure from 121 ± 15 mmHg to 66 ± 11 mmHg (P ≤ 0.05). In addition, exposure to 300 ppm H2S impaired arterial oxygenation (PaO2 114 ± 36 mmHg with air vs. 83 ± 23 mmHg with H2S; P ≤ 0.05). Conclusions Administration of up to 300 ppm H2S via ventilation of an

  11. Red blood cells augment transport of reactive metabolites of monocrotaline from liver to lung in isolated and tandem liver and lung preparations

    SciTech Connect

    Pan, L.C.; Lame, M.W.; Morin, D.; Wilson, D.W.; Segall, H.J. )

    1991-09-01

    Monocrotaline (MCT) is a pyrrolizidine alkaloid that causes pulmonary hypertension in rats by mechanisms which remain largely unknown. MCT is thought to be activated in the liver to a reactive intermediate that is transported to the lung where it causes endothelial injury. The authors previous pharmacokinetic work demonstrated significant sequestration of radioactivity in red blood cells (RBCs) of rats treated with (14C)MCT. To determine whether this RBC sequestration might be important in the transport of reactive MCT metabolites, they compared the effect of inclusion of RBCs in the perfusion buffer on the extent of covalent binding of (14C)MCT to rat lungs in tandem liver-lung preparations. The potential effect of RBCs in stabilizing reactive intermediates was evaluated by preperfusion of isolated liver preparations with (14C)MCT with and without RBCs, separation and washing of the RBC fraction, and subsequent (90 min later) perfusion of washed RBCs or buffer alone in isolated perfused lungs. Covalent binding to lung tissues was determined by exhaustive methanol/chloroform extractions of unbound label from homogenized lung tissue followed by scintillation counting of residual 14C. Covalent binding was expressed as picomole MCT molecular weight equivalents/mg protein. Comparison of the relative capability of these isolated organ preparations for conversion of MCT to polar metabolites was done by extraction and HPLC analysis of perfusate at the end of the experiment. Isolated livers converted 65-85% of MCT to polar metabolites compared with less than 5% conversion in the isolated lungs. Inclusion of RBCs in the buffer of tandem lung liver preparations perfused with 400 microM (14C)MCT increased the covalent binding to the lung from 97 {plus minus} 25 (buffer alone) to 182 {plus minus} 36 (buffer + RBC) pmol/mg protein.

  12. Identification of potential lung cancer biomarkers using an in vitro carcinogenesis model.

    PubMed

    Kim, Jung Eun; Koo, Kyung Hee; Kim, Yeul Hong; Sohn, Jeongwon; Park, Yun Gyu

    2008-12-31

    Lung cancer is one of the deadliest and commonly diagnosed neoplasms. Early diagnosis of this disease is critical for improving clinical outcome and prognosis. Because the early stages of lung cancer often produce no symptoms, it is necessary to identify biomarkers for early detection, prognostic evaluation, and recurrence monitoring of the cancer. To identify potential lung cancer biomarkers, we analyzed the differential protein secretion from transformed bronchial epithelial cells (1198 and 1170-I) as compared to immortalized normal bronchial epithelial cells (BEAS-2B) and non-transformed cells (1799) all of which are derived from BEAS-2B and represent multistage bronchial epithelial carcinogenesis. The proteins recovered from the conditioned media of the cells were separated on two-dimensional gels. There was little difference between the secretome of the BEAS-2B and 1799 cells, whereas the patterns between the transformed 1198 and 1170-I cells and non-transformed 1799 cells were significantly different. Using mass spectrometry and database search, we identified 20 proteins including protein gene product 9.5 (PGP9.5), translationally controlled tumor protein (TCTP), tissue inhibitors of metalloproteinases-2 (TIMP-2), and triosephosphate isomerase (TPI), that were either increased or decreased simultaneously in conditioned media of both 1198 and 1170-I cells. Furthermore, levels of PGP9.5, TCTP, TIMP-2, and TPI were significantly increased not only in the conditioned media of both transformed cell lines when compared to those of BEAS-2B and 1799 cells, but also in plasmas and tissues from lung cancer patients when compared to those in normal controls. We suggest the PGP9.5, TCTP, TIMP-2, and TPI as promising candidates for lung cancer serum biomarkers.

  13. Respiratory syncytial virus potentiates ABCA3 mutation-induced loss of lung epithelial cell differentiation.

    PubMed

    Kaltenborn, Eva; Kern, Suncana; Frixel, Sabrina; Fragnet, Laetitia; Conzelmann, Karl-Klaus; Zarbock, Ralf; Griese, Matthias

    2012-06-15

    ATP-binding cassette transporter A3 (ABCA3) is a lipid transporter active in lung alveolar epithelial type II cells (ATII) and is essential for their function as surfactant-producing cells. ABCA3 mutational defects cause respiratory distress in newborns and interstitial lung disease (ILD) in children. The molecular pathomechanisms are largely unknown; however, viral infections may initiate or aggravate ILDs. Here, we investigated the impact of the clinically relevant ABCA3 mutations, p.Q215K and p.E292V, by stable transfection of A549 lung epithelial cells. ABCA3 mutations strongly impaired expression of the ATII differentiation marker SP-C and the key epithelial cell adhesion proteins E-cadherin and zonula occludens-1. Concurrently, cells expressing ABCA3 mutation acquired mesenchymal features as observed by increased expression of SNAI1, MMP-2 and TGF-β1, and elevated phosphorylation of Src. Infection with respiratory syncytial virus (RSV), the most common viral respiratory pathogen in small children, potentiated the observed mutational effects on loss of epithelial and acquisition of mesenchymal characteristics. In addition, RSV infection of cells harboring ABCA3 mutations resulted in a morphologic shift to a mesenchymal phenotype. We conclude that ABCA3 mutations, potentiated by RSV infection, induce loss of epithelial cell differentiation in ATII. Loss of key epithelial features may disturb the integrity of the alveolar epithelium, thereby comprising its functionality. We suggest the impairment of epithelial function as a mechanism by which ABCA3 mutations cause ILD.

  14. FGFR as potential target in the treatment of squamous non small cell lung cancer.

    PubMed

    Tiseo, Marcello; Gelsomino, Francesco; Alfieri, Roberta; Cavazzoni, Andrea; Bozzetti, Cecilia; De Giorgi, Anna Maria; Petronini, Pier Giorgio; Ardizzoni, Andrea

    2015-06-01

    To date therapeutic options for squamous cell lung cancer patients remain scarce because no druggable targets have been identified so far. Aberrant signaling by FGFs (fibroblast growth factors) and FGFRs (fibroblast growth factors receptors) has been implicated in several human cancers and, particularly, in squamous non-small cell lung cancer (NSCLC). FGFR gene amplifications, somatic missense mutations, chromosomal translocations are the most frequent mechanisms able to induce aberrant activation of this pathway. Data from literature have established that the presence of an aberrant FGFR signaling has to be considered a possible negative prognostic factor but predictive of potential sensitivity to FGFR inhibitors. In the last years, clinical research efforts allowed to identify and evaluate promising FGFR inhibitors, such as monoclonal antibodies, ligand traps, non-selective or selective tyrosine kinase inhibitors. This review summarizes the current knowledge about FGFR alterations in NSCLC and the relative inhibitors in development, in particular in squamous NSCLC.

  15. Ultrastructural changes in the lung following exposure to perfluoroisobutylene (PFIB) and potentiation of PFIB-induced lung injury by post-exposure exercise

    SciTech Connect

    Lehnert, B.E.; Stavert, D.M.

    1990-01-01

    The authors investigated the kinetics of development of the injurious effects of perfluoroisobutylene (PFIB) in the lower respiratory tract of the rat as a function of inhaled mass concentration. We additionally examined if exercise performed after exposure to PFIB can potentiate the severity of expression of PFIB-induced lung injury, while also assessing how PFIB exposure may result in reductions in work performance capacity. The severity of PFIB-induced lung injury was found to be directly proportional to inhaled PFIB mass concentration whereas the post-exposure kinetics of development of the injurious response was inversely proportional to the mass concentration of PFIB, with post-exposure latency periods prior to the onset of detectable injury increasing with decreasing inhaled mass concentration. Exercise was found to potentiate PFIB-induced lung injury only after pulmonary edema was demonstrably present using lung gravimetric and light histopathologic criteria, even though ultrastructural observations indicated significant cellular changes occur during the latency period. Our collective findings suggest that pre-existing permeability changes in the lung are a necessary prerequisite for post-exposure exercise to exert a potentiating effect. Reductions in work performance capacity occurred only after the latency period, and such reductions proportionately scaled with the severity of pulmonary edema. 9 refs., 5 figs.

  16. Ultrasound perfusion signal processing for tumor detection

    NASA Astrophysics Data System (ADS)

    Kim, MinWoo; Abbey, Craig K.; Insana, Michael F.

    2016-04-01

    Enhanced blood perfusion in a tissue mass is an indication of neo-vascularity and a sign of a potential malignancy. Ultrasonic pulsed-Doppler imaging is a preferred modality for noninvasive monitoring of blood flow. However, the weak blood echoes and disorganized slow flow make it difficult to detect perfusion using standard methods without the expense and risk of contrast enhancement. Our research measures the efficiency of conventional power-Doppler (PD) methods at discriminating flow states by comparing measurement performance to that of an ideal discriminator. ROC analysis applied to the experimental results shows that power Doppler methods are just 30-50 % efficient at perfusion flows less than 1ml/min, suggesting an opportunity to improve perfusion assessment through signal processing. A new perfusion estimator is proposed by extending the statistical discriminator approach. We show that 2-D perfusion color imaging may be enhanced using this approach.

  17. A preliminary study of protoporphyrin-IX as a potential candidate for identification of lung cancer cells using fluorescence microscopy.

    PubMed

    Hyun, Dae-Sung; Kim, Hong-Tae; Jheon, Sang-Hoon; Park, Seung-Il; Kim, Jong-Ki

    2009-01-01

    There is need for a cheap, sensitive, and specific method to identify and localize early stage lung cancer. In order to improve the sensitivity of fluorescent agents that exhibit selective tumor uptake that are used as population screening tools for the detection of early lung cancer, a number of porphyrins including protoporphyrin-IX (PpIX) were tested. We stained lung cancer cells using three different sample preparation schemes for fluorescence microscopy. Lung tissues and sputum samples of nineteen patients were studied. Cells were collected on glass slides by touching tumor surfaces of surgically sectioned lung cancer tissue and normal regions of the lung during surgery. Filtered sputum cells were also collected. Cell-attached slides were stained with porphyrin using three different methods, including fixing (SM-1) prior to staining, and diluting porphyrin stock solutions in either RPMI-1640 medium (SM-2) or 100mM MES buffer (SM-3). Slides from normal lung tissue lacked fluorescent epithelial cells. Tumor slides containing typical lung cancer cells exhibited red fluorescence upon excitation through the soret band (400-450 nm) of porphyrin compounds. Tumor-selective staining was only observed on unfixed tumor slides that were incubated with PpIX in a RPMI-1640 culture medium (SM-3) used as a working solution for staining and washing. Protoporphyrin-IX is a potentially useful tumor-staining molecular agent for fluorescent location of cancer cell in sputum samples from lung cancer patients.

  18. Ventilation-perfusion-chest radiography match is less likely to represent pulmonary embolism if perfusion is decreased rather than absent.

    PubMed

    Kim, C K; Worsley, D F; Alavi, A

    2000-09-01

    The authors' goal was to determine whether the prevalence of pulmonary embolism in patients with matching ventilation-perfusion (V-Q) defects and chest radiographic opacities differs depending on the degree of perfusion deficit (absent versus decreased). The authors performed a retrospective analysis of the data obtained from the Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) study. In 233 patients, angiograms were of diagnostic quality for 275 lung zones that showed matching V-Q defects and chest radiographic opacities (triple matches). Of these, V-Q scans and chest radiographs from 217 patients with triple matches in 255 lung zones were retrieved and reviewed. Areas corresponding to chest radiographic opacities were scored as having either decreased perfusion or absent perfusion by consensus. Information regarding the presence or absence of pulmonary embolism in corresponding lung zones was obtained from the PIOPED database. The overall prevalence of pulmonary embolism in all lung zones with triple matches was 27% (69 of 255). Of the 255 areas of triple matches, the perfusion was decreased in 153 (60%) and absent in 102 (40%). The prevalence of pulmonary embolism in areas of triple matches with decreased perfusion and triple matches with absent perfusion was 13% (20 of 153) and 48% (49 of 102), respectively (P = 0.0001 by the chi-square test). When these were divided further by lung zones, triple matches with decreased perfusion and triple matches with absent perfusion in the upper-middle lung zone were associated with a prevalence of 0% (O of 44), and 25% (9 of 36), respectively. The prevalence of pulmonary embolism in areas of triple matches with decreased perfusion and triple matches with absent perfusion in the lower lung zone was 18% (20 of 109), and 61% (40 of 66), respectively. A V-Q/chest radiographic match is less likely to represent pulmonary embolism if perfusion is decreased rather than absent. The overall prevalence of pulmonary

  19. Application of an artificial neural network model for selection of potential lung cancer biomarkers.

    PubMed

    Ligor, Tomasz; Pater, Łukasz; Buszewski, Bogusław

    2015-05-06

    Determination of volatile organic compounds (VOCs) in the exhaled breath samples of lung cancer patients and healthy controls was carried out by SPME-GC/MS (solid phase microextraction- gas chromatography combined with mass spectrometry) analyses. In order to compensate for the volatile exogenous contaminants, ambient air blank samples were also collected and analyzed. We recruited a total of 123 patients with biopsy-confirmed lung cancer and 361 healthy controls to find the potential lung cancer biomarkers. Automatic peak deconvolution and identification were performed using chromatographic data processing software (AMDIS with NIST database). All of the VOCs sample data operation, storage and management were performed using the SQL (structured query language) relational database. The selected eight VOCs could be possible biomarker candidates. In cross-validation on test data sensitivity was 63.5% and specificity 72.4% AUC 0.65. The low performance of the model has been mainly due to overfitting and the exogenous VOCs that exist in breath. The dedicated software implementing a multilayer neural network using a genetic algorithm for training was built. Further work is needed to confirm the performance of the created experimental model.

  20. Potential Effects of Medicinal Plants and Secondary Metabolites on Acute Lung Injury

    PubMed Central

    Cornélio Favarin, Daniely; Robison de Oliveira, Jhony; Jose Freire de Oliveira, Carlo; de Paula Rogerio, Alexandre

    2013-01-01

    Acute lung injury (ALI) is a life-threatening syndrome that causes high morbidity and mortality worldwide. ALI is characterized by increased permeability of the alveolar-capillary membrane, edema, uncontrolled neutrophils migration to the lung, and diffuse alveolar damage, leading to acute hypoxemic respiratory failure. Although corticosteroids remain the mainstay of ALI treatment, they cause significant side effects. Agents of natural origin, such as medicinal plants and their secondary metabolites, mainly those with very few side effects, could be excellent alternatives for ALI treatment. Several studies, including our own, have demonstrated that plant extracts and/or secondary metabolites isolated from them reduce most ALI phenotypes in experimental animal models, including neutrophil recruitment to the lung, the production of pro-inflammatory cytokines and chemokines, edema, and vascular permeability. In this review, we summarized these studies and described the anti-inflammatory activity of various plant extracts, such as Ginkgo biloba and Punica granatum, and such secondary metabolites as epigallocatechin-3-gallate and ellagic acid. In addition, we highlight the medical potential of these extracts and plant-derived compounds for treating of ALI. PMID:24224172

  1. Potentially modifiable risk factors for atrial fibrillation following lung resection surgery: a retrospective cohort study.

    PubMed

    Lee, S H; Ahn, H J; Yeon, S M; Yang, M; Kim, J A; Jung, D M; Park, J H

    2016-12-01

    Atrial fibrillation is the most frequent arrhythmia after thoracic surgery and is associated with increased hospital costs, morbidity and mortality. In this study, we aimed to identify potentially modifiable risk factors for postoperative atrial fibrillation following lung resection surgery and to suggest possible measures to reduce risk. We retrospectively reviewed the medical records of 4731 patients who underwent lobectomy or more major lung resection over a 6-year period. Patients who developed atrial fibrillation postoperatively and required treatment were included in the postoperative atrial fibrillation group, while the remaining patients were assigned to the non-postoperative atrial fibrillation group. Risk factors for postoperative atrial fibrillation were analysed by multivariate analysis and propensity score matching. Overall, 12% of patients developed postoperative atrial fibrillation. Potentially modifiable risk factors for postoperative atrial fibrillation were excessive alcohol consumption (odds ratio (OR) = 1.48, 95% CI 1.08-2.02, p = 0.0140), red cell transfusion (2.70(2.13-3.43), p < 0.0001), use of inotropes (1.81(1.42-2.31), p < 0.0001) and open (vs. thoracoscopic) surgery (1.59(1.23-2.05), p < 0.0001). Compared with inotrope use, vasopressor administration was not related to postoperative atrial fibrillation. Use of steroids or thoracic epidural anaesthesia did not reduce the incidence of postoperative atrial fibrillation. We conclude that high alcohol consumption, red cell transfusion, use of inotropes and open surgery are potentially modifiable risk factors for postoperative atrial fibrillation. Pre-operative alcohol consumption needs to be addressed. Avoiding red cell transfusion and performing lung resection via video-assisted thoracoscopic surgery may reduce the incidence of postoperative atrial fibrillation and the administration of vasopressors rather than inotropes is preferred.

  2. Critical care in the ED: potentially fatal asthma and acute lung injury syndrome

    PubMed Central

    Hodder, Rick

    2012-01-01

    Emergency department clinicians are frequently called upon to assess, diagnose, and stabilize patients who present with acute respiratory failure. This review describes a rapid initial approach to acute respiratory failure in adults, illustrated by two common examples: (1) an airway disease – acute potentially fatal asthma, and (2) a pulmonary parenchymal disease – acute lung injury/acute respiratory distress syndrome. As such patients are usually admitted to hospital, discussion will be focused on those initial management aspects most relevant to the emergency department clinician. PMID:27147862

  3. The potential role of activin and follistatin in lung transplant dysfunction.

    PubMed

    Snell, James N; Westall, Glen P; Snell, Gregory I

    2015-01-01

    Activin A, a member of the transforming growth factor β super-family, is a key regulator of multiple biological pathways including the physiological processes of organ development and homeostasis; as well as the pathological processes of inflammation, remodelling and fibrosis. Dysregulation of activin A and its naturally occurring antagonist follistatin, contribute to the development of disease in multiple organ systems. In this review, we summarize the regulation of activin A, its dysregulated expression in a number of respiratory diseases and postulate its potential role in contributing to allograft dysfunction following lung transplantation.

  4. Calculation of lung flow differential after single-lung transplantation: a transesophageal echocardiographic study.

    PubMed

    Boyd, S Y; Sako, E Y; Trinkle, J K; O'Rourke, R A; Zabalgoitia, M

    2001-05-15

    Single-lung transplantation (SLT) is a viable option for patients with end-stage pulmonary disease. After successful SLT, pulmonary blood flow is preferentially shifted to the transplanted lung, creating a flow differential. Lack of flow differential may be indicative of potential vascular complications such as anastomotic stenosis or thrombosis. To assess the ability of transesophageal echocardiography (TEE) in estimating lung flow differential in patients undergoing SLT, biplane TEE was prospectively performed in 18 consecutive patients undergoing SLT early (24 to 72 hours), and in 10 of them late (3 to 6 months) after surgery. Right and left pulmonary vein flow were calculated as Qnu=A. VTI, where A, the pulmonary vein area, was derived as pi.(D/2)(2) and VTI is the velocity time integral of the pulmonary vein spectral display. Lung flow differential was calculated as the ratio of right (RQnu) or left (LQnu) pulmonary vein flow to total pulmonary venous flow (RQnu + LQnu). Lung perfusion imaging scintigraphy (technetium-99m) was used for comparison. Pulmonary vein velocity time integral of transplanted lung was significantly greater than that of native lung (34 +/- 9 vs 18 +/- 8 cm, p <0.001). Percent differential lung flow derived by perfusion imaging scintigraphy and by TEE showed a good correlation (r = 0.67, p <0.001). Pulmonary artery anastomoses were seen in all 12 right-lung recipients, and in 4 of the 6 left-lung recipients; no significant stenosis was noted in the arteries visualized. The pulmonary venous anastomoses were imaged in all patients. Small, nonocclusive pulmonary vein thrombi were seen in 1 patient. In conclusion, TEE is a useful method for calculating lung flow differential in patients undergoing SLT. In addition, TEE provides superb direct visualization of the venous and arterial anastomoses in most patients. Contrary to previous reports, the overall incidence of anastomotic complications is relatively low.

  5. Establishment of a human lung cancer cell line with high metastatic potential to multiple organs: gene expression associated with metastatic potential in human lung cancer.

    PubMed

    Nakano, Tetsuhiro; Shimizu, Kimihiro; Kawashima, Osamu; Kamiyoshihara, Mitsuhiro; Kakegawa, Seiichi; Sugano, Masayuki; Ibe, Takashi; Nagashima, Toshiteru; Kaira, Kyoichi; Sunaga, Noriaki; Ohtaki, Youichi; Atsumi, Jun; Takeyoshi, Izumi

    2012-11-01

    Convenient and reliable multiple organ metastasis model systems might contribute to understanding the mechanism(s) of metastasis of lung cancer, which may lead to overcoming metastasis and improvement in the treatment outcome of lung cancer. We isolated a highly metastatic subline, PC14HM, from the human pulmonary adenocarcinoma cell line, PC14, using an in vivo selection method. The expression of 34,580 genes was compared between PC14HM and parental PC14 by cDNA microarray analysis. Among the differentially expressed genes, expression of four genes in human lung cancer tissues and adjacent normal lung tissues were compared using real-time reverse transcription polymerase chain reaction. Although BALB/c nude mice inoculated with parental PC14 cells had few metastases, almost all mice inoculated with PC14HM cells developed metastases in multiple organs, including the lung, bone and adrenal gland, the same progression seen in human lung cancer. cDNA microarray analysis revealed that 981 genes were differentially (more than 3-fold) expressed between the two cell lines. Functional classification revealed that many of those genes were associated with cell growth, cell communication, development and transcription. Expression of three upregulated genes (HRB-2, HS3ST3A1 and RAB7) was higher in human cancer tissue compared to normal lung tissue, while expression of EDG1, which was downregulated, was lower in the cancer tissue compared to the normal lung. These results suggest that the newly established PC14HM cell line may provide a mouse model of widespread metastasis of lung cancer. This model system may provide insights into the key genetic determinants of widespread metastasis of lung cancer.

  6. An evaluation of preoperative and postoperative ventilation and perfusion lung scintigraphy in the screening for pulmonary embolism after elective orthopedic surgery

    SciTech Connect

    Keenan, A.M.; Palevsky, H.I.; Steinberg, M.E.; Hartman, K.M.; Alavi, A.; Lotke, P.A. )

    1991-01-01

    One hundred two patients undergoing elective knee or hip arthroplasty were studied with radionuclide ventilation scans (V) and perfusion scans (Q) preoperatively (preop) and postoperatively (postop) to assess their relative value in the diagnosis of asymptomatic pulmonary embolism (PE) after orthopedic surgery. Postop Q were read in combination with preop V and Q and postop V using prospective investigation of pulmonary embolism diagnosis (PIOPED) criteria. Of 25 postop Q interpreted as either high or intermediate probability for PE, preop Q were judged useful in 96%; the postop V were useful in 78%; and the preop V were not helpful in any of the cases. Of 63 postop Q interpreted as low probability, preop Q were useful in 74%; the postop V were useful in only 33%; and the preop V were useful in only one case. When postop Q were read as normal (14 cases), none of the three auxiliary studies were found to be useful. Overall, postop V were more helpful than preop Q in only 2%, and preop V contributed significantly in only 1%. This experience suggests that preop Q alone is the most useful adjunct to the postop Q in the postoperative evaluation for PE. The authors conclude that to screen for asymptomatic PE after elective orthopedic surgery, preop Q should be performed in all cases, preop V are not necessary, and postop V need be performed only if a baseline preop Q is not available.

  7. Multi-walled carbon nanotube-induced gene signatures in the mouse lung: potential predictive value for human lung cancer risk and prognosis

    PubMed Central

    Guo, Nancy L; Wan, Ying-Wooi; Denvir, James; Porter, Dale W; Pacurari, Maricica; Wolfarth, Michael G; Castranova, Vincent; Qian, Yong

    2012-01-01

    Concerns over the potential for multi-walled carbon nanotubes (MWCNT) to induce lung carcinogenesis have emerged. This study sought to (1) identify gene expression signatures in the mouse lungs following pharyngeal aspiration of well-dispersed MWCNT and (2) determine if these genes were associated with human lung cancer risk and progression. Genome-wide mRNA expression profiles were analyzed in mouse lungs (n=160) exposed to 0, 10, 20, 40, or 80 µg of MWCNT by pharyngeal aspiration at 1, 7, 28, and 56 days post-exposure. By using pairwise-Statistical Analysis of Microarray (SAM) and linear modeling, 24 genes were selected, which have significant changes in at least two time points, have a more than 1.5 fold change at all doses, and are significant in the linear model for the dose or the interaction of time and dose. Additionally, a 38-gene set was identified as related to cancer from 330 genes differentially expressed at day 56 post-exposure in functional pathway analysis. Using the expression profiles of the cancer-related gene set in 8 mice at day 56 post-exposure to 10 µg of MWCNT, a nearest centroid classification accurately predicts human lung cancer survival with a significant hazard ratio in training set (n=256) and test set (n=186). Furthermore, both gene signatures were associated with human lung cancer risk (n=164) with significant odds ratios. These results may lead to development of a surveillance approach for early detection of lung cancer and prognosis associated with MWCNT in the workplace. PMID:22891886

  8. Vasodilator-Stimulated Phosphoprotein Deficiency Potentiates PAR-1-induced Increase in Endothelial Permeability in Mouse Lungs

    PubMed Central

    Profirovic, Jasmina; Han, Jingyan; Andreeva, Alexandra V.; Neamu, Radu F.; Pavlovic, Sasha; Vogel, Stephen M.; Walter, Ulrich; Voyno-Yasenetskaya, Tatyana A.

    2010-01-01

    Vasodilator-stimulated phosphoprotein (VASP) is implicated in the protection of the endothelial barrier in vitro and in vivo. VASP function in thrombin signaling in the endothelial cells (ECs) is not known. For the first time we studied the effects of VASP deficiency on EC permeability and pulmonary vascular permeability in response to thrombin receptor stimulation. We provided the evidence that VASP deficiency potentiates the increase in endothelial permeability induced by activation of thrombin receptor in cultured human umbilical vein endothelial cells (HUVECs) and isolated mouse lungs. Using transendothelial resistance measurement, we showed that siRNA-mediated VASP downregulation in HUVECs leads to a potentiation of thrombin- and protease-activated receptor 1 (PAR-1) agonist-induced increase in endothelial permeability. Compared to control cells, VASP-deficient HUVECs had delayed endothelial junctional reassembly and abrogated VE-cadherin cytoskeletal anchoring in the recovery phase after thrombin stimulation, as demonstrated by immunofluorescence studies and cell fractionation analysis, respectively. Measurement of the capillary filtration coefficient in isolated mouse lungs demonstrated that VASP−/− mice have increased microvascular permeability in response to infusion with PAR-1 agonist compared to wild type mice. Lack of VASP led to decreased Rac1 activation both in VASP-deficient HUVECs after thrombin stimulation and VASP−/− mouse lungs after PAR-1 agonist infusion, indicating that VASP effects on thrombin signaling may correlated with changes in Rac1 activity. This study demonstrates that VASP may play critical and complex role in the regulation of thrombin-dependent disruption of the endothelial barrier function. PMID:20945373

  9. Electron transfer as a potential cause of diacetyl toxicity in popcorn lung disease.

    PubMed

    Kovacic, Peter; Cooksy, Andrew L

    2010-01-01

    Diacetyl, a butter-flavoring component, has recently attracted scientific and media attention because it has been implicated as an agent that induces popcorn lung disease in exposed plant workers. This disease, officially referred to as bronchiolitis obliterans, entails exposure-induced compromise to the lung's epithelial barrier function. In this review, we present a novel molecular mechanism (electron transfer, ET) designed to explain how diacetyl and its imine derivatives might interact to produce lung damage. We relate the fact that diacetyl and related compounds possess reduction potentials amenable to electron transfer (ET) in vivo. The electrochemical nature of these toxicants can potentially disrupt normal ET processes, generate reactive oxygen species (ROS), and participate in cell signaling events. Condensation of diacetyl with protein may also play a role in the toxicity caused by this compound. ET is a common feature of toxic substances, usually involving their metabolites which can operate per se or through reactions that generate ROS and oxidative stress (OS). Examples of agents capable of ET are quinone and metal compounds, aromatic nitro compounds, and iminium salts. Among compounds that generate ET, the alpha-dicarbonyl ET class, of which diacetyl is a member, is much less studied. This review emphasizes diacetyl as an agent that acts through oxidative processes to cause its effects. However, we also treat related substances that appear to act by a similar mechanism. This mechanism forms a theoretical framework capable of describing the mechanism by which diacetyl may induce its effects and is in accord with various physiological activities displayed by other alpha-dicarbonyl substances. Examples of substances that may act by mechanisms similar to that displayed by diacetyl include cyclohexane-1,2-dione, marinopyrroles, reactive carbonyl species, the bacterial signaling agent DPD, and advanced glycation end products.

  10. The reflex effects of alterations in lung volume on systemic vascular resistance in the dog

    PubMed Central

    Daly, M. de Burgh; Hazzledine, Julie L.; Ungar, A.

    1967-01-01

    1. The reflex effects of alterations in lung volume on systemic vascular resistance have been studied in anaesthetized dogs under conditions in which the systemic circulation was perfused at constant blood flow. The pressures in the isolated perfused carotid sinuses and aortic arch, and the arterial blood PO2 and PCO2 were maintained constant. 2. A maintained inflation of the lungs produced by injection of air into the trachea caused a fall in systemic arterial perfusion pressure, indicating vasodilatation. The size of the systemic vasodilator response varied directly with the pressure and volume of gas used to inflate the lungs. A similar effect was observed when the tidal volume of lungs ventilated by an intermittent positive pressure was increased. 3. Collapse of the lungs by creating a pneumothorax in closed-chest spontaneously breathing animals evoked a systemic vasoconstrictor response which was reversed when the lungs were re-expanded. 4. These vasodilator responses were abolished by dividing the pulmonary branches of the thoracic vagosympathetic nerves. Evidence is presented that the afferent fibres run in the cervical vagosympathetic nerves and through the stellate ganglia. 5. The responses were unaffected by atropine, but were abolished by hexamethonium, guanethidine and by bretylium tosylate, indicating that they are mediated via the sympathetic nervous system. 6. Evidence is presented that the lungs are a constant course of afferent impulses inhibiting the `vasomotor centre', and that the lung inflation—systemic vasodilator reflex is a potential mechanism operating in eupnoeic breathing. PMID:6032204

  11. Microvesicles Derived From Human Mesenchymal Stem Cells Restore Alveolar Fluid Clearance in Human Lungs Rejected for Transplantation.

    PubMed

    Gennai, S; Monsel, A; Hao, Q; Park, J; Matthay, M A; Lee, J W

    2015-09-01

    The need to increase the donor pool for lung transplantation is a major public health issue. We previously found that administration of mesenchymal stem cells "rehabilitated" marginal donor lungs rejected for transplantation using ex vivo lung perfusion. However, the use of stem cells has some inherent limitation such as the potential for tumor formation. In the current study, we hypothesized that microvesicles, small anuclear membrane fragments constitutively released from mesenchymal stem cells, may be a good alternative to using stem cells. Using our well established ex vivo lung perfusion model, microvesicles derived from human mesenchymal stem cells increased alveolar fluid clearance (i.e. ability to absorb pulmonary edema fluid) in a dose-dependent manner, decreased lung weight gain following perfusion and ventilation, and improved airway and hemodynamic parameters compared to perfusion alone. Microvesicles derived from normal human lung fibroblasts as a control had no effect. Co-administration of microvesicles with anti-CD44 antibody attenuated these effects, suggesting a key role of the CD44 receptor in the internalization of the microvesicles into the injured host cell and its effect. In summary, microvesicles derived from human mesenchymal stem cells were as effective as the parent mesenchymal stem cells in rehabilitating marginal donor human lungs. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

  12. An alternative method for neonatal cerebro-myocardial perfusion

    PubMed Central

    Luciani, Giovanni Battista; De Rita, Fabrizio; Faggian, Giuseppe; Mazzucco, Alessandro

    2012-01-01

    Several techniques have already been described for selective cerebral perfusion during repair of aortic arch pathology in children. One method combining cerebral with myocardial perfusion has also been proposed. A novel technique is reported here for selective and independent cerebro-myocardial perfusion for neonatal and infant arch surgery. Technical aspects and potential advantages are discussed. PMID:22307393

  13. Potentially Functional Polymorphisms in POU5F1 Gene Are Associated with the Risk of Lung Cancer in Han Chinese

    PubMed Central

    Niu, Rui; Wang, Yuzhuo; Zhu, Meng; Wen, Yifan; Sun, Jie; Shen, Wei; Cheng, Yang; Zhang, Jiahui; Jin, Guangfu; Ma, Hongxia; Hu, Zhibin; Shen, Hongbing; Dai, Juncheng

    2015-01-01

    POU5F1 is a key regulator of self-renewal and differentiation in embryonic stem cells and may be associated with initiation, promotion, and progression in cancer. We hypothesized that functional polymorphisms in POU5F1 may play an important role in modifying the lung cancer risk. To test this hypothesis, we conducted a case-control study to explore the association between 17 potentially functional SNPs in POU5F1 gene and the lung cancer risk in 1,341 incident lung cancer cases and 1,982 healthy controls in a Chinese population. We found that variant alleles of rs887468 and rs3130457 were significantly associated with increased risk of lung cancer after multiple comparison (OR = 1.29, 95% CI: 1.11–1.51, Pfdr = 0.017 for rs887468; OR = 1.29, 95% CI: 1.10–1.51, Pfdr = 0.034 for rs3130457, resp.). In addition, we detected a significant interaction between rs887468 genotypes and smoking status on lung cancer risk (P = 0.017). Combined analysis of these 2 SNPs showed a significant allele-dosage association between the number of risk alleles and increased risk of lung cancer (Ptrend < 0.001). These findings indicate that potentially functional polymorphisms in POU5F1 gene may contribute to lung cancer susceptibility in a Chinese population. PMID:26824036

  14. [The lung].

    PubMed

    Martinod, Emmanuel; Uzunhan, Yurdagül; Radu, Dana M; Seguin, Agathe; Boddaert, Guillaume; Valeyre, Dominique; Planès, Carole; Carpentier, Alain

    2011-10-01

    Lung transplantation is still the only curative treatment for end-stage pulmonary diseases. The results remain poor, however, because of the limited availability of lung donors, chronic rejection, and complications related to immunosuppressive therapy. The use of a bioartificial lung generated from autologous cells could offer a solution. We have demonstrated that in vivo epithelial and cartilage regeneration of the airways is feasible with the use of an aortic tissue matrix. Other studies show that in vitro and in vivo airway regeneration, respectively, can be obtained by using bio-engineering and heterotopic allograft implantation. A more complex challenge is the creation of an artificial lung Indeed, this would require the use of an elastic matrix that can promote regeneration of the different lung components (airways, alveoli, vessels) over a large surface area, thus allowing ventilation, blood perfusion and gas exchanges. Recent studies have demonstrated the possibility of in vitro and in vivo regeneration of lung tissue from autologous cells, and especially stem cells. This emerging research field is currently dominated by the use of decellularized lung matrices and autologous epithelial and endothelial cells. Implantation of such a recellularized matrix in animals has proved the feasibility of a functional bio-artificial lung. The first human transplantation of a bio-artificial lung should be possible within 10-20 years.

  15. A potential role for estrogen in cigarette smoke-induced microRNA alterations and lung cancer

    PubMed Central

    Cohen, Amit; Smith, Yoav

    2016-01-01

    Alteration in the expression of microRNAs (miRNAs) is associated with oncogenesis and cancer progression. In this review we aim to suggest that elevated levels of estrogens and their metabolites inside the lungs as a result of cigarette smoke exposure can cause widespread repression of miRNA and contribute to lung tumor development. Anti-estrogenic compounds, such as the components of cruciferous vegetables, can attenuate this effect and potentially reduce the risk of lung cancer (LC) among smokers. PMID:27413713

  16. Seawater-drowning-induced acute lung injury: From molecular mechanisms to potential treatments

    PubMed Central

    Jin, Faguang; Li, Congcong

    2017-01-01

    Drowning is a crucial public safety problem and is the third leading cause of accidental fatality, claiming ~372,000 lives annually, worldwide. In near-drowning patients, acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) is one of the most common complications. Approximately 1/3 of near-drowning patients fulfill the criteria for ALI or ARDS. In the present article, the current literature of near-drowning, pathophysiologic changes and the molecular mechanisms of seawater-drowning-induced ALI and ARDS was reviewed. Seawater is three times more hyperosmolar than plasma, and following inhalation of seawater the hyperosmotic seawater may cause serious injury in the lung and alveoli. The perturbing effects of seawater may be primarily categorized into insufficiency of pulmonary surfactant, blood-air barrier disruption, formation of pulmonary edema, inflammation, oxidative stress, autophagy, apoptosis and various other hypertonic stimulation. Potential treatments for seawater-induced ALI/ARDS were also presented, in addition to suggestions for further studies. A total of nine therapeutic strategies had been tested and all had focused on modulating the over-activated immunoreactions. In conclusion, seawater drowning is a complex injury process and the exact mechanisms and potential treatments require further exploration. PMID:28587319

  17. Clove (Syzygium aromaticum L.), a potential chemopreventive agent for lung cancer.

    PubMed

    Banerjee, Sarmistha; Panda, Chinmay Kr; Das, Sukta

    2006-08-01

    Spices and flavoring plants part rich in supposedly health-promoting phytochemicals are currently receiving much attention as a possible source of cancer chemopreventive compounds. Clove, the sun-dried unopened flower bud from the plant Syzygium aromaticum L. is a commonly used spice and food flavor. In the pres