Ex-vivo Lung Research Articles

635 Ex-Vivo Lung Evaluation of Pre-Arrest Heparinization in Donation after Cardiac Death

635 Ex-Vivo Lung Evaluation of Pre-Arrest Heparinization in Donation after Cardiac Death

323 Successful Transplantation of Unusable Donor Lungs Using Ex-Vivo Lung Perfusion: The Newcastle Experience

Lungs from brain dead (DBD) and donation after circulatory death (DCD) donors are very susceptible to acute injury often rendering them unusable. Ex-vivo lung perfusion (EVLP) has been proposed as a way of objectively assessing and reconditioning unusable donor lungs for clinical use. Data on conversion rates and clinical outcomes after EVLP reconditioned donor lungs are transplanted is very limited.

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

OBJECTIVE: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.METHODS: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 (4°C, 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.RESULTS: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.CONCLUSIONS: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.

Donor Lung Selection Criteria and Surgical Application at University of Pittsburgh

Lung transplantation is the standard treatment for patients with end-stage lung disease. Unfortunately scarce source of donor organs, particularly in lungs, limits this selected treatment to very few recipients each year. To decrease waiting list deaths and provide organs to more diverse recipient population, widening selection criteria of donor lungs was offered. Besides expanded criteria in organ selection to increase lung transplant surgery, donation after cardiac death and ex-vivo lung perfusion were introduced to current medicine. University of Pittsburgh in last decade doubled its lung transplant volume by extending the acceptance criteria for donor lungs for which many other centers would decline in first line or some selected centers may try ex-vivo perfusion protocols on these lungs. Nonetheless successful transplant surgery requires successful donor procurement surgery. Based on this practice, we wanted to review the Pittsburgh model of expanding lung donor selection criteria and surgery for donor lung procurement.

Metformin attenuates ventilator-induced lung injury.

IntroductionDiabetic patients may develop acute lung injury less often than non-diabetics; a fact that could be partially ascribed to the usage of antidiabetic drugs, including metformin. Metformin exhibits pleiotropic properties which make it potentially beneficial against lung injury. We hypothesized that pretreatment with metformin preserves alveolar capillary permeability and, thus, prevents ventilator-induced lung injury.MethodsTwenty-four rabbits were randomly assigned to pretreatment with metformin (250 mg/Kg body weight/day per os) or no medication for two days. Explanted lungs were perfused at constant flow rate (300 mL/min) and ventilated with injurious (peak airway pressure 23 cmH2O, tidal volume ≈17 mL/Kg) or protective (peak airway pressure 11 cmH2O, tidal volume ≈7 mL/Kg) settings for 1 hour. Alveolar capillary permeability was assessed by ultrafiltration coefficient, total protein concentration in bronchoalveolar lavage fluid (BALF) and angiotensin-converting enzyme (ACE) activity in BALF.ResultsHigh-pressure ventilation of the ex-vivo lung preparation resulted in increased microvascular permeability, edema formation and microhemorrhage compared to protective ventilation. Compared to no medication, pretreatment with metformin was associated with a 2.9-fold reduction in ultrafiltration coefficient, a 2.5-fold reduction in pulmonary edema formation, lower protein concentration in BALF, lower ACE activity in BALF, and fewer histological lesions upon challenge of the lung preparation with injurious ventilation. In contrast, no differences regarding pulmonary artery pressure and BALF total cell number were noted. Administration of metformin did not impact on outcomes of lungs subjected to protective ventilation.ConclusionsPretreatment with metformin preserves alveolar capillary permeability and, thus, decreases the severity of ventilator-induced lung injury in this model.

Are three patients better than one?

Lung transplantation represents the only effective strategy for treatment of end stage respiratory failure. Nevertheless its clinical application remains quite limited and a significant discrepancy between the number of LTx performed and its real need still remains evident [1]. Therefore patients wait for LTx for a long period with a high mortality rate while on the waiting list. For this reason we wrote a review with a provocative title in which we wondered if LTx was a clinical reality or should be conversely considered an experimental procedure [2]. In the recent period, we are witnessing epochal changes at different levels in the field of lung transplantation. On the side of donor management, application of particular ventilatory strategies may be effective in increasing the rate of lung suitability [3]. After the initial experience published by Steen [4], very recently an important article from the Toronto Lung Transplant Program showed how initially rejected or sub-optimal grafts can be successfully transplanted after the recovery of a normal pulmonary function, obtained by ex-vivo lung perfusion [5]. ECMO and interventional lung assist devices have been introduced in the clinical armamentarium for the management of lung transplant recipients suffering from severe deterioration of pulmonary function. As it happens for heart and kidney recipients, novel technological advances of the devices nowadays available allow their applications as a bridge to transplant also for LTx. These technologies not only increase the life expectancy of patients in the waiting list but also avoid the necessity of mechanical ventilation and lead these patients to LTx in better conditions even without the need of an intensive care unit stay [6–8]. Waiting time for LTx is highly dependent from somatic characteristics of recipients and very small patients may wait for a suitable graft for a longer period. For these patients, living lobar lung transplant may be one of the possible strategies to overcome this issue. Chen et al. describe excellent results regarding pulmonary function on living lobar lung transplant donors. This is an important message but a word of caution is mandatory. In comparison with other solid transplant performed using living donor graft (e.g. kidney), living lobar lung transplant is a highly demanding procedure performed on ‘healthy’ patients (the donor). In fact, the procedure Correspondence Massimo Boffini, Cardiac Surgery Department, San Giovanni Battista Hospital, University of Turin, Corso Bramante 88, Turin 18100, Italy. Tel.: +39 011 6335511; fax: +39 011 6336130; e-mail: massimo.boffini@unito.it

Ex Vivo Evaluation of Lungs from Donation after Cardiac Death after Recent Cardiac Surgery with Cardiopulmonary Bypass

Lack of suitable donor lungs is still a major limitation of lung transplantation. Extended donor acceptance criteria combined with innovative assessment tools can be used to expand the number of suitable organs. We describe a successful transplantation of lungs retrieved from a donor who had undergone aortic root replacement 9 days before donation after cardiac death. The lungs were assessed using ex-vivo lung perfusion.

Extracorporeal lung perfusion

The number of patients listed for lung transplantation largely exceeds the number of available transplantable organs because of both a shortage of organ donors and a low utilization rate of lungs from those donors due to injuries acquired during the process of brain death and intensive care unit (ICU) care. A novel strategy for donor lung preservation - ex-vivo lung perfusion (EVLP) - that keeps the organ at physiological protective conditions has shown great promise to increase lung utilization by reassessing, treating, and repairing injured donor lungs prior to transplantation. A first clinical trial using EVLP has shown the method to be safe and to allow for reassessment and improvement in function of lungs from high-risk donor lungs prior to transplantation. When these lungs were transplanted, low rates of primary graft dysfunction were achieved, and the early outcomes were similar to those with conventionally selected and transplanted lungs. Preclinical studies have shown a great potential of EVLP as a platform for the delivery of novel simple and advanced therapies to repair injured organs ex vivo and thus further increase the donor lung utilization rate. EVLP triggers a new era in lung transplantation. This method will allow for more and better organs to become available. Several experimental studies, clinical case reports, and a clinical trial have shown the safety of EVLP and the numerous potentials of EVLP.

Cytokine Expression Profile in Human Lungs Undergoing Normothermic Ex-Vivo Lung Perfusion

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.

89 Early Outcomes of Bilateral Sequential Single Lung Transplantation after Ex-Vivo Lung Evaluation and Reconditioning

Purpose Ex-vivo lung perfusion (EVLP) is a novel approach for extended evaluation and/or reconditioning of donor lungs not meeting standard ISHLT criteria for transplantation (tx). This is a prospective evaluation of 11 consecutive EVLP runs performed between January 2009 and September 2010 at a single institution. Methods and Materials Lungs offered and rejected for routine tx were evaluated and procured normally if they met the inclusion criteria for EVLP. Thus obtained grafts were implanted in the EVLP circuit and reperfused according to the institutional protocol using acellular supplemented STEEN Solution™ up to a target flow rate of 40% of the donor's calculated flow at a cardiac index of 3.0 l/min/m2 with a LA pressure <5mmHg and PA pressure <15mmHg. After re-warming to 37°C, grafts were ventilated with a 6-8ml/kg(donor weight) tidal volume with a respiratory rate of 7-8/minute, an IE ratio of 1:2 and PEEP of 5-10cmH20. Hemodynamic and respiratory data was monitored continuously and the graft was underwent hourly clinical assessments. Results Donor data: n=11, age 44.81±8.82 years, cause of death: intracranial hemorrhage - 10(91%), stroke - 1(9%), history of smoking 7(64%), average pack year 19.57±8.59 years, mechanical ventilation time 98.36±91.60 hours, CXR: abnormal - 10(91%), normal - 1(9%). EVLP: Mean duration 146.04±31.06 minutes. Arterial PaO2 before termination of the circuit improved significantly compared to the last pre-retrieval value: 55.95±9.46 vs 40.4±14.92 kPa (p<0.05). After ex-vivo evaluation and reconditioning, 5 (45%) pairs of lungs were successfully transplanted. Recipient data: Age 41.8±15.69 years, underlying disease: cystic fibrosis - 2(40%), emphysema - 3(60%). Median ITU stay was 7 (range 3–72) days, median follow-up 91 (range 67–269) days, with a 30 day survival rate of 100%. There was one late death (day 203) due to pneumonia. Conclusions EVLP facilitates assessment and reconditioning of borderline lungs with a conversion rate to tx of 45% and excellent short-term survival. Ex-vivo lung perfusion (EVLP) is a novel approach for extended evaluation and/or reconditioning of donor lungs not meeting standard ISHLT criteria for transplantation (tx). This is a prospective evaluation of 11 consecutive EVLP runs performed between January 2009 and September 2010 at a single institution. Lungs offered and rejected for routine tx were evaluated and procured normally if they met the inclusion criteria for EVLP. Thus obtained grafts were implanted in the EVLP circuit and reperfused according to the institutional protocol using acellular supplemented STEEN Solution™ up to a target flow rate of 40% of the donor's calculated flow at a cardiac index of 3.0 l/min/m2 with a LA pressure <5mmHg and PA pressure <15mmHg. After re-warming to 37°C, grafts were ventilated with a 6-8ml/kg(donor weight) tidal volume with a respiratory rate of 7-8/minute, an IE ratio of 1:2 and PEEP of 5-10cmH20. Hemodynamic and respiratory data was monitored continuously and the graft was underwent hourly clinical assessments. Donor data: n=11, age 44.81±8.82 years, cause of death: intracranial hemorrhage - 10(91%), stroke - 1(9%), history of smoking 7(64%), average pack year 19.57±8.59 years, mechanical ventilation time 98.36±91.60 hours, CXR: abnormal - 10(91%), normal - 1(9%). EVLP: Mean duration 146.04±31.06 minutes. Arterial PaO2 before termination of the circuit improved significantly compared to the last pre-retrieval value: 55.95±9.46 vs 40.4±14.92 kPa (p<0.05). After ex-vivo evaluation and reconditioning, 5 (45%) pairs of lungs were successfully transplanted. Recipient data: Age 41.8±15.69 years, underlying disease: cystic fibrosis - 2(40%), emphysema - 3(60%). Median ITU stay was 7 (range 3–72) days, median follow-up 91 (range 67–269) days, with a 30 day survival rate of 100%. There was one late death (day 203) due to pneumonia. EVLP facilitates assessment and reconditioning of borderline lungs with a conversion rate to tx of 45% and excellent short-term survival.

418 Reconditioning of Gastric Acid Injured Lung Grafts with Surfactant in Lung Transplantation

Purpose: The number of available donor lungs is still the limiting factor in lung transplantation. We have recently shown during ex-vivo lung evaluation that diluted surfactant lavage improved the graft function after gastric acid aspiration. In the present study we hypothesized that the same treatment in lungs injured by gastric acid aspiration may improve graft function in transplanted porcine lungs. Methods and Materials: Lung injury was induced by intratracheal instillation of 1 ml/kg Oroacid® by a flexible fiberoptic bronchoscope under direct vision into the left main bronchus and the animals were ventilated for 24 hours thereafter. Following harvest the donor lungs were stored at 4°C for 4 hours. In control group (n 4) left lung transplantation was performed without any treatment. In surfactant treated group (n 6) the recipients received intratracheal diluted surfactant (1 ml/kg) lavage just before reperfusion and ventilation. During 7 hours of reperfusion hemodynamic and ventilatory variables were recorded hourly. Bronchoalveolar lavage (BAL) was performed at the end of the experiment for bubble surfactometry and further analysis. Results: Surfactant lavage resulted in lower mean pulmonary artery pressure, lower airway pressure and better oxygenation compared to control group (p 0.001). BAL IL-6 level and neutrophil percentage at the end of the experiment was significantly higher in control compared to surfactant group (p 0.05). Minimal surface tension was significantly lower in surfactant group compared to controls (p 0.05). Conclusions: In this model diluted surfactant administration before reperfusion attenuates the injury and improves the graft function in lung transplantation.

419 The Consumption of Glucose during Ex-Vivo Lung Perfusion (EVLP) Correlate with Lung Edema

419 The Consumption of Glucose during Ex-Vivo Lung Perfusion (EVLP) Correlate with Lung Edema

421 Myeloperoxidase Tissue Level (MPO) Reflects Successful Repair of Donor Lung Injury by Ex-Vivo Lung Perfusion (EVLP)

421 Myeloperoxidase Tissue Level (MPO) Reflects Successful Repair of Donor Lung Injury by Ex-Vivo Lung Perfusion (EVLP)

Early outcomes of bilateral sequential single lung transplantation after ex-vivo lung evaluation and reconditioning

Ex vivo lung perfusion (EVLP) is a novel approach for extended evaluation and/or reconditioning of donor lungs not meeting standard International Society for Heart and Lung Transplantation criteria for transplantation. We retrospectively evaluated 13 consecutive EVLP runs between January 2009 and December 2010. Lungs rejected for routine transplantation were implanted to the EVLP circuit and reperfused using acellular supplemented Steen Solution (Vitrolife, Göteborg, Sweden) up to a target flow rate of 40% of the donor's calculated flow at a cardiac index of 3.0 liters/min/m(2); target left atrial pressure < 5 mm Hg; and pulmonary artery pressure < 15 mm Hg. Mechanical ventilation was introduced after rewarming to 32°C: tidal volume, 6 to 8 ml/kg; respiratory rate, 7 to 8 breaths/min; duration of inspiration/expiration (I/E) ratio, 1:2; and positive end-expiratory pressure, 5 to 10 cm H(2)O. Hemodynamic and respiratory data monitoring with hourly clinical assessment were performed. Donor data, conversion rate to transplantation, and recipient outcome were analyzed. Donor data (n = 13) were: age, 44.23 ± 8.33 years; female/male, 8:5; cause of death: intracranial hemorrhage, 11 (85%), stroke, 1 (7.5%), hypoxic brain injury, 1 (7.5%); smoking history, 9 (69%), 17.44 ± 8.92 pack-years; mechanical ventilation, 102.6 ± 91.92 hours; chest x-ray imaging: abnormal, 12 (92.5%); normal, 1 (7.5%). EVLP: mean 141 ± 28.83 minutes. Arterial partial pressure of oxygen/fraction of inspired oxygen 100% before termination of the circuit vs pre-retrieval value: 57.32 ± 9.1 vs 42.36 ± 14.13 kPa (p < 0.05). Six (46%) pairs of donor lungs were transplanted. Median follow-up was 297.5 days (range, 100-390 days), with 100% survival at 3 months. EVLP may facilitate assessment and/or reconditioning of borderline lungs, with a conversion rate of 46 % and good short-term survival.

92 Donor Accidental Aspiration Injury – Can We Correct It by Ex-Vivo-Lung-Perfusion (EVLP)?

Purpose After establishing a porcine pulmonary aspiration injury model we evaluated reconditioning/treatment options during ex vivo lung perfusion. Methods and Materials After inducing aspiration injury lungs were perfused for 6 hrs in our ex-vivo lung perfusion circuit (leucocyte filter, heparin coated system, perfusate Steen solution + erythrocytes, Hb5mg/dl) according to standardized protocol. Three groups (n=7 each) were studied: Gr.1 reperfusion only, Gr.2 reperf.+extensive medical treatment incl. NO ventilation, Gr.3 like Gr.2+ATG. Respiratory and hemodynamic parameters were monitored pre-harvest and hourly during reperfusion. Pre- and postreperfusion wet-dry ratio was calculated, histology performed. Judgement of transplantability based on standard donor criteria plus evaluation of pulmonary deflation index (PDI) ≤2 (index grading 1-5; 1=normal to 5=macroscopic frothy edema). Results In Gr.1 one lung failed after 4hrs of reperfusion, while in Gr.2 and 3 all lungs were perfused for 6hrs. Compliance was equal in Gr.2 and 3 (59±8 vs. 59±13 ml/mbar), but significantly better than in Gr.1 (32±16 ml/mbar) at study end-point; PVR was lowest using ATG (1590±412 Gr.1 vs. 585±150 Gr.2 vs. 357±225 Gr.3 dynes). Pulmonary Oxygenation Capacity decreased in Gr.1 and remained stable in Gr.2/3 (172±115 Gr.1 vs. 383±45 Gr.2 vs. 322±57 mmHg Gr.3). Macroscopic evaluation revealed significantly better results in Gr.3 (PDI: 3.8±0.8 Gr.1 vs. 2.3±0.6 Gr.2 vs. 1.6±0.5 Gr.3). Histology and wet-dry ratio confirmed results. In Gr.1 all lungs failed transplantability criteria, in Gr.2 47% were transplantable, in Gr.3 using ATG even 86%. Conclusions Using appropriate medical treatment including ATG administration EVLP allows reversal even of pulmonary aspiration injury. After establishing a porcine pulmonary aspiration injury model we evaluated reconditioning/treatment options during ex vivo lung perfusion. After inducing aspiration injury lungs were perfused for 6 hrs in our ex-vivo lung perfusion circuit (leucocyte filter, heparin coated system, perfusate Steen solution + erythrocytes, Hb5mg/dl) according to standardized protocol. Three groups (n=7 each) were studied: Gr.1 reperfusion only, Gr.2 reperf.+extensive medical treatment incl. NO ventilation, Gr.3 like Gr.2+ATG. Respiratory and hemodynamic parameters were monitored pre-harvest and hourly during reperfusion. Pre- and postreperfusion wet-dry ratio was calculated, histology performed. Judgement of transplantability based on standard donor criteria plus evaluation of pulmonary deflation index (PDI) ≤2 (index grading 1-5; 1=normal to 5=macroscopic frothy edema). In Gr.1 one lung failed after 4hrs of reperfusion, while in Gr.2 and 3 all lungs were perfused for 6hrs. Compliance was equal in Gr.2 and 3 (59±8 vs. 59±13 ml/mbar), but significantly better than in Gr.1 (32±16 ml/mbar) at study end-point; PVR was lowest using ATG (1590±412 Gr.1 vs. 585±150 Gr.2 vs. 357±225 Gr.3 dynes). Pulmonary Oxygenation Capacity decreased in Gr.1 and remained stable in Gr.2/3 (172±115 Gr.1 vs. 383±45 Gr.2 vs. 322±57 mmHg Gr.3). Macroscopic evaluation revealed significantly better results in Gr.3 (PDI: 3.8±0.8 Gr.1 vs. 2.3±0.6 Gr.2 vs. 1.6±0.5 Gr.3). Histology and wet-dry ratio confirmed results. In Gr.1 all lungs failed transplantability criteria, in Gr.2 47% were transplantable, in Gr.3 using ATG even 86%. Using appropriate medical treatment including ATG administration EVLP allows reversal even of pulmonary aspiration injury.

Ex-Vivo Human Lung Tumor Model: Use for Temperature Measurements during Thermal Ablation of NSCLC

In the present study we used an ex-vivo human lung cancer model to compare temperature diffusion during thermal ablation using one laser fiber to that of a two-fiber approach. Furthermore, we examined whether there was a difference between temperature diffusion in normal lung tissue and tumor tissue during laser ablation. 48 resected lung specimens containing non-small cell lung cancer were connected to a perfusion/ventilation apparatus and treated with 1 (22 specimens, group 1) or, in a second experiment, with 1 (13 specimens, group 2) or 2 (13 specimens, group 3) laser fibers. During tumor ablation, temperatures were measured interstitially every 5 sec. Laser ablation was followed by the taking of samples of 13 specimens for histological examination. For comparison we performed laser ablation in 7 specimens with normal lung tissue. Laser treatment and temperature control were technically feasible in all samples. Thirty min after starting laser ablation with 1 fiber, a temperature of 61 ± 17 °C was achieved in group 1 at a distance of 10 mm from the laser fiber and a temperature of 74 ± 11 °C was achieved in group 2 (p = 0.1). In the middle between two active laser fibers placed 20 mm apart, a temperature of 93 ± 7 °C was achieved. The temperature reached in normal lung tissue after 20 min of laser ablation was 77 ± 15 °C at a distance of 10 mm from the laser fiber. The ex-vivo model allowed performance of laser-induced thermal ablation in the perfused and ventilated lung. The use of two laser fibers increases the achieved temperatures significantly (p < 0.05). Temperatures reached in normal lung tissue were as high as in tumor tissue (p = 0.24).

The contribution of airway and lung tissue ischemia to primary graft dysfunction

Primary graft dysfunction (PGD) is the primary obstacle to short-term survival for post-lung transplant patients. PGD is a form of acute lung injury secondary to donor brain death and ischemia-reperfusion damage to the allograft affecting 10-25% of all lung transplant recipients. This article reviews the significant role of allograft ischemia in the phenotypic presentation of PGD and the evidence for activation and disruption of normal cellular pathways for the development and long-term sequelae. Pathways implicated in the pathogenesis of PGD resultant from tissue ischemia include abnormalities in coagulation and fibrinolysis, epithelial cell injury, endothelial cell dysfunction, chemotaxis, and alterations in cell adhesion. Blood and bronchoalveolar lavage fluid biomarkers from these pathways have been increasingly identified as useful for diagnosing and predicting the development of severe PGD. Future efforts at preventing and treating severe PGD should focus on techniques for altering the pathways involved in PGD pathogenesis. Ex-vivo lung perfusion and transduction with interleukin-10 are promising modalities for preventing PGD and expanding the available lung transplant donor pool.

Thoracic organs: current preservation technology and future prospects; part 1: lung

The critical organ shortage has forced lung transplant teams to extend their donor criteria, thereby compromising a good early outcome in the recipient. Better preservation solutions for longer storage are welcomed to further reduce incidence of primary graft dysfunction. New ex-vivo techniques to assess and to condition lungs prior to transplantation are hoped to increase the number of available pulmonary grafts. Although no prospective clinical trial has been carried out so far, clinical and experimental evidence suggest that an extracellular solution is currently the preservation fluid of choice for lung transplantation. The combination of an antegrade and retrograde pulmonary flush and technique to control reperfusion and ventilation are becoming common practice, although the evidence to support this method is low. Ex-vivo lung perfusion to assess and to recondition lungs has been demonstrated to be well tolerated and effective in small clinical series. New extracellular preservation solutions have contributed in decreasing the incidence of primary graft dysfunction over the last decade leaving more room to extend the donor criteria and ischemic time. Ex-vivo lung perfusion is now on the horizon as a potential method to prolong the preservation time and to resuscitate lungs of inferior quality.

503: Does the Ex-Vivo Lung Evaluation System Affect Post-Transplant Graft Function in Swine Donation after Cardiac Death (DCD) Lung Transplantation?

503: Does the Ex-Vivo Lung Evaluation System Affect Post-Transplant Graft Function in Swine Donation after Cardiac Death (DCD) Lung Transplantation?

504: The Effect of Ex-Vivo Perfusion on the Inflammatory Profile of the Donor Lung

Ex-vivo lung perfusion (EVLP) may allow reconditioning of borderline donor lungs prior to transplantation. Although studies have demonstrated an improvement in physiological function, the effect of EVLP on lung inflammation is not yet established. We hypothesized that EVLP might contribute to reconditioning by decreasing pro-inflammatory cytokine levels in the donor lung.