Argon and xenon ventilation during prolonged ex vivo lung perfusion.

Background: 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.

Retrograde flush is more protective than heparin in the uncontrolled donation after circulatory death lung donor.

Background: Formation of microthrombi after circulatory arrest is a concern for the development of reperfusion injury in lung recipients from donation after circulatory death (DCD) donors. In this isolated lung reperfusion study, we compared the effect of postmortem heparinization with preharvest retrograde pulmonary flush or both.

Methods: Domestic pigs (n = 6/group) were sacrificed by ventricular fibrillation and left at room temperature for 1 h.

Evaluating lung injury at increasing time intervals in a murine brain death model.

Introduction: Only 15%-25% of brain death (BD) donors match the ideal donor criteria for lung transplantation. Lung injury may evolve in the hours after onset of brain death, but the evolution over time has not been well studied in lung. The aim of this study was to evaluate lung injury at different time points after BD using a murine model.

Medium-term outcome after lung transplantation is comparable between brain-dead and cardiac-dead donors.

Background: Donation after cardiac death (DCD) to overcome the donor organ shortage is now moving into the clinical setting, but the medium-term outcome after DCD lung transplantation (LTx) remains largely unknown.

Methods: In this retrospective study, DCD LTx recipients (n = 21) were compared with a cohort of donation-after-brain-death (DBD) LTx recipients (n = 154) transplanted between February 2007 and July 2010. Immediate (post)operative outcome was evaluated by assessing need for peri-operative extracorporeal membrane oxygenation (ECMO), time to extubation, hospital discharge and primary graft dysfunction (PGD) within the first 48 hours.

Task-independent metrics to assess the data quality of medical registries using the European Society of Thoracic Surgeons (ESTS) Database.

Objective: The quality of data collected into a database is of paramount importance in every analysis. No standardized methods are available to quantify the quality of data in medical registries. Expanding the work done in other fields, we aimed at developing a methodological approach to measure the quality of a thoracic surgical database, by using the European Society of Thoracic Surgeons (ESTS) Database.

A porcine model of acute lung injury by instillation of gastric fluid.

Background: About 15% of donor lungs are declined because of aspiration contributing to current organ shortage. The aim was to develop a porcine lung injury model by gastric juice (GJ) instillation to study different pretransplant treatment strategies.

Materials And Methods: Pigs (n = 6/group) were anesthetized and monitored.

The mode of death in the non-heart-beating donor has an impact on lung graft quality.

Objective: We hypothesised that the agonal phase prior to cardiac death may negatively influence the quality of the pulmonary graft recovered from non-heart-beating donors (NHBDs). Different modes of death were compared in an experimental model.

Methods: Non-heparinised pigs were divided into three groups (n=6 per group).

Obliterative bronchiolitis following lung transplantation: from old to new concepts?

Lung transplantation has come of age and is now considered a valid treatment for selected patients with end-stage lung disease. In recent years, survival rates have much improved, although the development of chronic rejection, characterized by a progressive and irreversible decline in FEV(1), which is clinically defined as bronchiolitis obliterans syndrome (BOS) remains the major obstacle to long-term survival. Extensive research efforts with special emphasis on innate immunity have recently led to new insights with the identification of at least two different phenotypes: on the one hand there is an azithromycin-responsive phenotype (the so-called neutrophilic reversible allograft/airways dysfunction (NRAD), on the other hand there is an azithromycin-unresponsive phenotype (the fibroproliferative form of BOS or classical obliterative bronchiolitis).

Retrograde flush following warm ischemia in the non-heart-beating donor results in superior graft performance at reperfusion.

Background: The use of non-heart-beating donors (NHBD) has been propagated as an alternative to overcome the scarcity of pulmonary grafts. The presence of postmortem thrombi, however, is a concern for the development of primary graft dysfunction. In this isolated lung reperfusion study, we looked at the need and the best route of preharvest pulmonary flush.

Lung transplantation: a 15-year single-center experience.

During the past decade, the outcome after lung transplantation has improved due to a substantial reduction in the immediate postoperative and perioperative mortality that resulted from better surgical techniques, anaesthetic and perioperative management and more intense antibiotic, antifungal and antiviral prophylaxis. However, according to the International Society for Heart and Lung transplantation (ISHLT) Registry, the long-term survival has not improved much in recent years and mortality is most often due to the development of chronic allograft dysfunction, infections, posttransplant lymphoproliferative disorders and other tumours. Although treatment options have improved for most of these issues, therapy for chronic allograft dysfunction has been very disappointing.

Azithromycin reduces airway inflammation in a murine model of lung ischaemia reperfusion injury.

Clinical studies revealed that azithromycin reduces airway neutrophilia during chronic rejection after lung transplantation. Our aim was to investigate the possible effect of azithromycin on ischaemia-reperfusion injury. Azithromycin or water was administered to mice every other day during 2 weeks (n = 6/group).

N-acetyl cysteine pre-treatment attenuates inflammatory changes in the warm ischemic murine lung.

Background: The warm ischemic period in non-heart-beating donor lungs may contribute to a higher degree of ischemia-reperfusion injury after lung transplantation. We investigated the impact and timing of administration of N-acetyl cysteine (NAC) on inflammatory parameters.

Methods: Ischemia (I) was induced by clamping the hilum of the left lung for 90 minutes, and some protocols were followed by reperfusion (R) for 4 hours.

N-acetyl cysteine attenuates the inflammatory response in warm ischemic pig lungs.

Background: Lungs donated after cardiac death (DCD) may significantly reduce current organ shortage. However, the warm ischemic period following circulatory arrest may enhance ischemia-reperfusion injury (IRI). We investigated the possible therapeutic effect of N-acetyl cysteine (NAC), a potent anti-oxidative agent on IRI in a porcine ex vivo lung reperfusion model.

Retrograde flush following topical cooling is superior to preserve the non-heart-beating donor lung.

Objective: The use of non-heart-beating donors (NHBD) has been propagated as an alternative to overcome the scarcity of pulmonary grafts. Formation of microthrombi after circulatory arrest, however, is a major concern for the development of reperfusion injury. We looked at the effect and the best route of pulmonary flush following topical cooling in NHBD.

Primary cryptococcal cellulitis in a lung transplant recipient.

In organ transplant recipients there remains controversy whether cutaneous cryptococcal infection represents a primary infection or a manifestation of disseminated cryptococcosis. We describe a lung transplant patient who developed primary cryptococcal cellulitis in the immediate post-operative period. At presentation, disseminated disease was excluded.

Comparative study of donor lung injury in heart-beating versus non-heart-beating donors.

Objective: The use of non-heart-beating donors (NHBD) has been advocated as an alternative to overcome the critical organ shortage in lung transplantation despite the warm ischemic period that may result in primary graft dysfunction. On the contrary, brain death in the heart-beating donor (HBD) may be an underestimated risk factor for donor lung injury. We postulated that 60 min of warm ischemia in the NHBD is less detrimental to the lung than the pathophysiological changes after brain death in the HBD.

Impact of warm ischemia on different leukocytes in bronchoalveolar lavage from mouse lung: possible new targets to condition the pulmonary graft from the non-heart-beating donor.

Background: The use of non-heart-beating donors (NHBDs) for lung transplantation is a possible alternative for increasing the number of organs available. The warm ischemic period after circulatory arrest may contribute to a higher degree of primary graft dysfunction, resulting from ischemia-reperfusion injury (IRI). A better understanding of the role of inflammatory cells during the warm ischemic interval may be useful for developing new therapeutic strategies against IRI.

Nebulized N-acetyl cysteine protects the pulmonary graft inside the non-heart-beating donor.

Background: The use of lungs from non-heart-beating donors (NHBD) might significantly alleviate the organ shortage. The tolerable warm ischemic period after cardiac arrest, however, is limited to approximately 1 hour. If the lung could be safely protected inside the cadaver, this time period may be prolonged.

Effect of azithromycin on bronchiectasis and pulmonary function in a heart-lung transplant patient with severe chronic allograft dysfunction: a case report.

Azithromycin has been shown to be beneficial in several diseases with chronic neutrophilic inflammation of the airways, such as cystic fibrosis and bronchiolitis obliterans syndrome (BOS) after lung transplantation. Up to now, however, its healing effect on bronchiectasis has never been demonstrated. We report a heart-lung transplant patient who developed chronic rejection (BOS stage 3) with the appearance of gross bronchiectasis on a spiral computed tomography (CT) chest scan.

IL-1beta in bronchial lavage fluid is a non-invasive marker that predicts the viability of the pulmonary graft from the non-heart-beating donor.

Background: Viability testing of the pulmonary graft retrieved from the non-heart-beating donor (NHBD) is mandatory for successful outcome after lung transplantation. Functional assessment by ex vivo reperfusion, however, remains a cumbersome procedure. In this study, therefore, we wanted to investigate the possible value of the proinflammatory cytokines interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) measured in bronchial lavage fluid (BLF) in predicting functional outcome of the pulmonary graft after reperfusion.