Lung volume reduction surgery is safe and feasible after initial endobronchial valve treatment for emphysema patients.

BACKGROUND AND OBJECTIVES: Bronchoscopic lung volume reduction with endobronchial valves is a guideline treatment leading to improved pulmonary function, exercise tolerance, and quality of life, in patients with advanced emphysema, severe hyperinflation and no collateral ventilation. After valve-treatment, loss of the initial lung volume reduction effect can occur, as well as local valve-induced complications such as persistent hemoptysis. In these cases, a surgical lobectomy can be considered to achieve similar efficacy outcomes. We evaluated the safety and feasibility of a video assisted thoracoscopic surgery -lobectomy after valve-treatment. METHODS: This single-center retrospective study included patients who underwent an elective lobectomy after previous valve-treatment. Data was evaluated for safety and efficacy for the additional surgical procedure. RESULTS: Twenty one patients (73% female, median age 67 (7) years, FEV1 29 (7) %pred, and residual volume 223 (58) %pred) were included. There was no 90 days mortality, and no post-operative Intensive Care admissions. Pulmonary infections (14%) and prolonged air leak (14%) were the most common complications. In patients who underwent surgery due to loss or lack of effect of valve-treatment, a lobectomy led to a significant improvement in pulmonary function; median FEV1 +75 (193)ml (p < 0.013), Forced Vital Capacity +450 (572) ml (p 0.001), Residual Volume -665 (715) ml (p 0.005). In patients who underwent a lobectomy because of complications of valve-treatment, all complications were resolved after surgery. CONCLUSION: We demonstrate that an elective lobectomy after an initial valve-treatment is safe, feasible, and restores the lung volume reduction effect.

The additional diagnostic value of virtual bronchoscopy navigation in patients with pulmonary nodules - The NAVIGATOR study.

BACKGROUND: The number of solitary pulmonary nodules to be evaluated is expected to increase and therefore we need to improve diagnostic and therapeutic tools to approach these nodules. To prevent patients from futile invasive procedures and receiving treatment without histological confirmation of cancer, we evaluated the value of virtual bronchoscopy navigation to obtain a diagnosis of the solitary pulmonary nodule in a real-world clinical setting. METHODS: In the NAVIGATOR single center, prospective, observational cohort study patients underwent a virtual bronchoscopy navigation procedure with or without guide sheet tunnelling to assess a solitary pulmonary nodule. Nodules were considered not accessible if a diagnosis could not be obtained by either by CT-guided transthoracic biopsy or conventional bronchoscopy. RESULTS: Between February 2021 and January 2022 35 patients underwent the virtual bronchoscopy navigation procedure. The overall diagnostic yield was 77% and was dependent on size of the nodule and chosen path, with highest yield in lesions with an airway path. Adverse events were few and manageable. CONCLUSION: Virtual bronchoscopy navigation with or without sheet tunnelling is a new technique with a good diagnostic yield, also in patients in whom previously performed procedures failed to establish a diagnosis and/or alternative procedures are considered not feasible based on expected yield and/or safety. Preventing futile or more invasive procedures like surgery or transthoracic punctures with a higher complication rate is beneficial for patients, and allowed treatment adaptation in two-third of the analyzed patient population.

Establishing an economical and widely accessible donation after circulatory death animal abattoir model for lung research using ex vivo lung perfusion.

BACKGROUND: Ex vivo lung perfusion (EVLP), is a platform that allows simultaneous testing and treatment of the lungs. However, use of EVLP is costly and requires access to lab animals and accompanying facilities. To increase the use of EVLP for research, we developed a method to perform EVLP using abattoir procured lungs. Furthermore, we were also able to significantly decrease costs. METHODS: Six pair of lungs were procured from abattoir sheep. The lungs were then flushed and stored in ice for 3 h. A low-flow (20% of cardiac output) approach, a tidal volume of 6 ml/kg bodyweight and total perfusion time of 3 h were chosen. Perfusion fluids and circuits were self-made. Lung biopsies, perfusate collection, respiratory values, circulatory pressures were recorded and hourly blood gas analyses were performed. RESULTS: Mean pO2 remained stable from 60 min (49.3 ± 7.1 kPa) to 180 min (51.5 kPa ± 8.0), p = 0.66. Pulmonary artery pressure remained ≤15 mm Hg and the left atrial pressure remained between 3 and 5 mm Hg and peak respiratory pressures ≤20 cmH2 O. Lactate dehydrogenase increased from start (96.3 ± 56.4 U/L) to the end of perfusion (315.8 ± 85.0 U/L), p < 0.05. No difference was observed in ATP between procurement and post-EVLP, 129.7 ± 37.4 µmol/g protein to 132.0 ± 23.4 µmol/g, p = 0.92. CONCLUSIONS: Sheep lungs, acquired from an abattoir, can be ex vivo perfused under similar conditions as lab animal lungs with similar results regarding e.g., oxygenation and ATP restoration. Furthermore, costs can be significantly reduced by making use of this abattoir model. By increasing accessibility and lowering costs for experiments using lung perfusion, more results may be achieved in the field of lung diseases.

Long-term outcome and bridging success of patients evaluated and bridged to lung transplantation on the ICU.

BACKGROUND: Evaluating and bridging patients to lung transplantation (LTx) on the intensive care unit (ICU) remains controversial, especially without a previous waitlist status. Long term outcome data after LTx from ICU remains scarce. We compared long-term survival and development of chronic lung allograft dysfunction (CLAD) in elective and LTx from ICU, with or without previous waitlist status. METHODS: Patients transplanted between 2004 and 2018 in 2 large academic Dutch institutes were included. Long-term survival and development of CLAD was compared in patients who received an elective LTx (ELTx), those bridged and transplanted from the ICU with a previous listing status (BTT), and in patients urgently evaluated and bridged on ICU (EBTT). RESULTS: A total of 582 patients underwent a LTx, 70 (12%) from ICU, 39 BTT and 31 EBTT. Patients transplanted from ICU were younger than ELTx (46 vs 51 years) and were bridged with mechanical ventilation (n = 42 (60%)), extra corporeal membrane oxygenation (n = 28 (40%)), or both (n = 21/28). Bridging success was 48% in the BTT group and 72% in the EBTT group. Patients bridged to LTx on ICU had similar 1 and 5 year survival (86.8% and 78.4%) compared to elective LTx (86.8% and 71.9%). This was not different between the BTT and EBTT group. 5 year CLAD free survival was not different in patients transplanted from ICU vs ELTx. CONCLUSION: Patients bridged to LTx on the ICU with and without prior listing status had excellent short and long-term patient and graft outcomes, and was similar to patients electively transplanted.

Analysis of Released Circulating Tumor Cells During Surgery for Non-Small Cell Lung Cancer.

PURPOSE: Tumor cells from patients with lung cancer are expelled from the primary tumor into the blood, but difficult to detect in the peripheral circulation. We studied the release of circulating tumor cells (CTCs) during surgery to test the hypothesis that CTC counts are influenced by hemodynamic changes (caused by surgical approach) and manipulation. EXPERIMENTAL DESIGN: Patients undergoing video-assisted thoracic surgery (VATS) or open surgery for (suspected) primary lung cancer were included. Blood samples were taken before surgery (T0) from the radial artery (RA), from both the RA and pulmonary vein (PV) when the PV was located (T1) and when either the pulmonary artery (T2 open) or the PV (T2 VATS) was dissected. The CTCs were enumerated using the CellSearch system. Single-cell whole-genome sequencing was performed on isolated CTCs for aneuploidy. RESULTS: CTCs were detected in 58 of 138 samples (42%) of 31 patients. CTCs were more often detected in the PV (70%) compared with the RA (22%, P < 0.01) and in higher counts (P < 0.01). After surgery, the RA but not the PV showed less often CTCs (P = 0.02). Type of surgery did not influence CTC release. Only six of 496 isolated CTCs showed aneuploidy, despite matched primary tumor tissue being aneuploid. Euploid so-called CTCs had a different morphology than aneuploid. CONCLUSIONS: CTCs defined by CellSearch were identified more often and in higher numbers in the PV compared with the RA, suggesting central clearance. The majority of cells in the PV were normal epithelial cells and outnumbered CTCs. Release of CTCs was not influenced by surgical approach.

First experience with ex vivo lung perfusion for initially discarded donor lungs in the Netherlands: a single-centre study.

OBJECTIVES: Despite progress in lung transplantation (LTx) techniques, a shortage of donor lungs persists worldwide. Ex vivo lung perfusion (EVLP) is a technique that evaluates, optimizes and enables transplantation of the lungs that would otherwise have been discarded. Herein, we present our centre's first EVLP experiences between July 2012 and June 2016, when we performed 149 LTxs. METHODS: It was a single-centre, retrospective analysis of a prospectively collected database. The EVLP group (n = 9) consisted of recipients who initially received discarded donor lungs that were reconditioned using EVLP. The non-EVLP (N-EVLP) group (n = 18) consisted of data-matched patients receiving conventional quality lungs in the conventional way. Both groups were compared on primary graft dysfunction (PGD) grades 0-3, pulmonary function, chronic lung allograft dysfunction and survival. RESULTS: In the EVLP group, 33% (3/9) developed PGD1 at 72 h post-LTx. In the N-EVLP group, 11% (2/18) developed PGD1, 6% (1/18) PGD2 and 11% (2/18) PGD3 at 72 h post-LTx. At 3 and 24 months post-LTx, forced expiratory volume in 1 s as percentage of predicted was similar in the EVLP (78% and 92%) and N-EVLP groups (69% and 89%). Forced vital capacity as a percentage of predicted was comparable in the EVLP (77% and 93%) and N-EVLP groups (68% and 101%). Chronic lung allograft dysfunction was diagnosed in 1 N-EVLP patient at 2 years post-LTx. Three-year survival was 78% (7/9) (the EVLP group) vs 83% (15/18) (the N-EVLP group). CONCLUSIONS: These results are in line with the existing literature suggesting that transplantation of the previously discarded lungs recovered by EVLP leads to equal outcomes compared to conventional LTx methods.

Surgical experience and patient-related restrictions predict the adequacy of cervical mediastinoscopy in non-small cell lung carcinoma lymph node staging.

BACKGROUND: Until recently, cervical mediastinoscopy was considered to be the reference standard for mediastinal staging for Non-Small Cell Lung Carcinoma (NSCLC). In the absence of metastases, mediastinal lymph node involvement is the most important prognostic factor and as such it determines therapeutic strategies. In this study we evaluated the adequacy of cervical mediastinoscopy in NSCLC lymph node staging in a large university hospital over more than a decade. In addition, we determined the influence of: (1) surgeon's experience (2) video-assisted mediastinoscopy (VAM) and (3) patient-related restrictions (PRR) on the adequacy of lymph node sampling. METHODS: Between January 2001 and December 2014, 225 patients underwent cervical mediastinoscopy for lymph node staging. Surgical and histological data were reviewed. Thirty-day follow-up was available for all patients. Lymph node sampling was considered adequate when stations 4 L, 4R and 7 were sampled (ESTS guidelines). A surgeon was considered to be experienced when he or she performed at least 40 procedures during the study-period. RESULTS: Intraoperative mortality was 0%. Thirty-day mortality was 1.3%. Overall adequacy of lymph node sampling was 56%. Univariate and multivariate logistic regression analyses of lymph node sampling adequacy revealed level of surgical experience and PRR as independent predictors of lymph node sampling adequacy. CONCLUSIONS: Surgical experience and PRR independently predict the adequacy of cervical mediastinoscopy in NSCLC lymph node staging. VAM does not independently predict the adequacy of mediastinal lymph node sampling. In light of the expected further decline in mediastinoscopy numbers, we recommend to limit this procedure exclusively to the armamentarium of the experienced thoracic surgeon.

Robot-assisted thoracoscopic lobectomy as treatment of a giant bulla.

BACKGROUND: A bulla is a marked enlarged space within the parenchyma of the lung. Bullae may cause dyspnea by compressing healthy lung parenchyma and can cause a pneumothorax. Also, bullae are associated with malignancy, therefore surgical bullectomy is indicated on preventive basis. This case is unique and therefore valuable because of the remarkable presentation, innovative treatment and the spectacular improvement of lung function and socio-economic performance of the patient. CASE PRESENTATION: In this case report we describe the presentation, minimally invasive surgical treatment by means of a robot-assisted lobectomy and postoperative outcome of a young patient with a giant congenital bulla of the left upper lobe. CONCLUSIONS: In this case robot-assisted lobectomy has shown spectacular improvement of lung function and fast-track recovery with beneficial socio-economic performance in a young patient with a giant congenital bulla.

CT-guided percutaneous hookwire localization increases the efficacy and safety of VATS for pulmonary nodules.

BACKGROUND AND OBJECTIVES: The diagnosis of pulmonary nodules of unknown origin is challenging, and such nodules are not always suitable for transthoracic needle biopsy. With the advent of video assisted thoracic surgery (VATS) and CT-guided percutaneous hookwire localization (CT-PHL) we hypothesized that the combination of these two procedures will improve early diagnosis. METHODS: Selection criteria were a nodule not well approachable with fine needle biopsy and the therapeutic consequences of a diagnosis as assessed by the multidisciplinary oncology board. Efficacy and safety of the combination of CT-PHL prior to VATS was studied in terms of, histological diagnosis, complete resection rate, complications, conversion rate to thoracotomy, and duration of procedures. RESULTS: A total of 150 pulmonary nodules were located and resected in 150 patients. The median nodule diameter was 9 mm (range 4-24) and located within 30 mm of the pleural surface (median 7, range 0-29). The resection was complete in 96%, and in 100% a definitive histological diagnosis was obtained. Complications requiring intervention during the CT-procedure occurred in 11 patients (7.3%). Complications of VATS consisted of major complications (2.0%) and minor complications (4.0%). The 30 Day mortality was 1.4% and in hospital mortality 0.7%. Conversion to thoracotomy occurred in 4.7% patients. Median CT-localization time was 25 min (range 5-72), median VATS time was 49 min (range 14-169). CONCLUSIONS: CT-PHL is a very efficient and safe procedure prior to VATS for pulmonary nodules and allows in 96% radical resection with a diagnostic accuracy of 100%.

A staged approach for a lung-liver transplant patient using ex vivo reconditioned lungs first followed by an urgent liver transplantation.

Combined lung-liver transplantation is a logistically challenging procedure hampered by shortage of organ donors. We describe the case of a young patient with end-stage lung disease due to of cystic fibrosis and liver cirrhosis who needed combined lung-liver transplantation. The long waiting for this caused an interesting clinical dilemma. We decided to change our policy in this situation by listing him only for the lung transplantation and to apply for a high urgent liver transplantation if the liver failed after the lung transplantation. This strategy enabled us to use lungs treated with ex vivo lung perfusion (EVLP) from an unsuitable donor after circulatory death. After conditioning for 4 h via EVLP, the pO2 was 59.7 kPa. The lungs were transplanted successfully. He developed an acute-on-chronic liver failure for which he received a successful liver transplantation 19 days after the lung transplantation.

Removal of a giant intrathoracic cyst from the anterior mediastinum.

A 45-year-old caucasian man with progressive dyspnea appeared to have a giant intrathoracic cyst in the anterior mediastinum encasing the heart and compressing both lungs. He underwent successful removal of the cyst through a median sternotomy. Recovery was uneventful. Gross examination revealed a thin-walled cyst filled with clear fluid. Microscopic histopathologic examination revealed a cyst wall lined by cubic cells and underlying loose connective tissue with remnants of thymic tissue. The definitive diagnosis was an intrathoracic (simple) mesothelial cyst. An intrathoracic mesothelial cyst is a benign, generally asymptomatic tumor that can be located in the anterior cardiophrenic angle, the paravertebral or paratracheal regions, or in the anterior mediastinum. It can become rather large before it becomes symptomatic, at which point surgical removal is generally warranted.

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. This was followed by 2.5 h of topical cooling. In control group [C], no heparin and no pulmonary flush were administered. In group [R], lungs were flushed with Perfadex in a retrograde way before explantation. In group [H], heparin (300 IU/kg) was administered 10 min after cardiac arrest followed by closed chest massage for 2 min. In the combined group, animals were heparinized and the lungs were explanted after retrograde flush [HR]. The left lung was assessed for 60 min in an ex vivo reperfusion model. RESULTS: Pulmonary vascular resistance at 50 and 55 min was significantly lower in [R] and [HR] groups compared with [C] and [H] groups (P < 0.01 and P < 0.001) and at 60 min in [R], [H], and [HR] groups compared with [C] group (P < 0.001). Oxygenation, compliance, and plateau airway pressure were more stable in [R] and [HR] groups. Plateau airway pressure was significantly lower in [R] group compared with the [H] group at 60 min (P < 0.05). No significant differences in wet-dry weight ratio were observed between the groups. CONCLUSIONS: This study suggests that preharvest retrograde flush is more protective than postmortem heparinization to prevent reperfusion injury in lungs recovered from donation after circulatory death donors.

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

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.

The use of non-heart-beating lung donors category III can increase the donor pool.

OBJECTIVE: The use of non-heart-beating (NHB) lung donors has been propagated as an alternative besides heart-beating (HB) lung donors to overcome organ shortage. We evaluated the effectiveness of NHB lung transplantation. METHODS: The donor and recipient data of all 35 NHB category III lung transplantations (LTx) between January 2005 and December 2009 were reviewed. For comparison, we collected recipient and donor data of a cohort of 77 HB lung transplantations. In both groups, we assessed survival, primary graft dysfunction (PGD), forced expiratory volume in 1s (FEV(1)), acute rejection, and bronchiolitis obliterans syndrome (BOS). RESULTS: Thirty-five NHB lung transplantations were performed, five single LTx and 30 bilateral LTx in 12 male and 23 female patients. The donor oxygenation capacity was 61 kPa (interquartile range (IQR), 56-64). Warm ischemia time in the donor was 29 min (IQR, 24-30). Cold ischemic time of the last implanted lung was 458 min (IQR, 392-522). Cardiopulmonary bypass was used 13 times. PGD (1-3) was observed in 45% of the patients at T0, in 42% at T24, in 53% at T48, and in 50% at T72. PGD 3 decreased from 24% at T0 to 6% at T72. The use of nitric oxide (NO) within 24h after transplantation was necessary in three patients with successful weaning in all. There was no significant difference for donor and recipient characteristics between NHB and HB lung transplantations. Survival, occurrence of PGD, and acute rejection was equal to the HB cohort. The incidence of BOS was lower in the NHB group. The measured FEV(1) tended to be better in the NHB group. CONCLUSION: Lungs from nonheparinized category III NHB donors are well suited for transplantation and can safely increase the donor pool.

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). Animals in group I [FIB] were sacrificed by ventricular fibrillation resulting in immediate circulatory arrest. In group II [EXS], animals were exsanguinated (45+/-11 min). In group III [HYP], hypoxic cardiac arrest (13+/-3 min) was induced by disconnecting the animal from the ventilator. Blood samples were taken pre-mortem in HYP and EXS for measurement of catecholamine levels. After 1 h of in situ warm ischaemia, unflushed lungs were explanted and stored for 3 h (4 degrees C). Left lung performance was then tested during 60 min in our ex vivo reperfusion model. Total protein concentration in bronchial lavage fluid was measured at the end of reperfusion. RESULTS: Pre-mortem noradrenalin (mcg l(-1)) concentration (baseline: 0.03+/-0) increased to a higher level in HYP (50+/-8) vs EXS (15+/-3); p=0.0074. PO(2) (mmHg) at 60 min of reperfusion was significantly worse in HYP compared to FIB (445+/-64 vs 621+/-25; p<0.05), but not to EXS (563+/-51). Pulmonary vascular resistance (dynes s cm(-5)) was initially higher in EXS (p<0.001) and HYP (NS) vs FIB (15824+/-5052 and 8557+/-4933 vs 1482+/-61, respectively) but normalised thereafter. Wet-to-dry weight ratio was higher in HYP compared to FIB (5.2+/-0.3 vs 4.7+/-0.2, p=0.041), but not to EXS (4.9+/-0.2). Total protein (g l(-1)) concentration was higher, although not significant in HYP and EXS vs FIB (18+/-6 and 13+/-4 vs 4.5+/-1.3, respectively). CONCLUSION: Pre-mortem agonal phase in the NHBD induces a sympathetic storm leading to capillary leak with pulmonary oedema and reduced oxygenation upon reperfusion. Graft quality appears inferior in NHBD lungs when recovered in controlled (HYP) vs uncontrolled (EXS and FIB) setting.

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. METHODS: Domestic pigs were sacrificed by ventricular fibrillation and divided in 3 groups (n = 6 per group). After 1 h of in situ warm ischemia, lungs in group I were retrieved unflushed (NF). In group II, lungs were explanted after an anterograde flush (AF) through the pulmonary artery. Finally, in group III, lungs were explanted after a retrograde flush (RF) via the left atrium. After 3 h of cold storage, the left lung was assessed for 60 min in our ex vivo reperfusion model. Wet-to-dry weight ratio (W/D) was calculated after reperfusion. RESULTS: Pulmonary vascular resistance (dynes x sec x cm(-5)) was 1145 +/- 56 (RF) versus 1560 +/- 123 (AF) and 1435 +/- 95 (NF) at 60 min of reperfusion (P < 0.05). Oxygenation and compliance were higher and plateau airway pressure was lower in RF versus AF and NF, although the difference did not reach statistical significance. No differences in W/D were observed between groups after reperfusion. Histological examination revealed fewer microthrombi in the left lung in RF compared with AF and NF. CONCLUSION: RF of lungs from NHBD improves graft function by elimination of microthrombi from the pulmonary vasculature, resulting in lower pulmonary vascular resistance upon reperfusion.

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). On the 14th day, the left lung was clamped to induce ischaemia (90 min). In two additional groups, animals underwent the same protocol, followed by 4 h of reperfusion. Two control groups were included with thoracotomy only. Inflammatory parameters and oxidative stress were measured in broncho-alveolar lavage of the left lung. Leukocytes, lymphocytes, neutrophils, 8-isoprostane and IL-1beta levels after ischaemia and reperfusion were significantly reduced in mice treated with azithromycin. There was a trend towards lower IL-6 and KC levels. A significant correlation was seen between 8-isoprostanes and neutrophils (Pearson r = 0.72; P = 0.0086), IL-6 (Pearson r = 0.84; P = 0.0006), KC (Pearson r = 0.88; P = 0.0002) and IL-1beta (Pearson r = 0.62; P = 0.0326). We conclude (i) that azithromycin reduces inflammation and oxidative stress in our IRI model, and (ii) that oxidative stress is correlated with the number of neutrophils and IL-6, KC and IL-1beta levels after ischaemia and reperfusion. Azithromycin should be further investigated as a novel drug to prevent lung ischaemia-reperfusion injury.

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. Mice were divided into nine groups (n = 6/group): three control groups ([sham] (thoracotomy only), [I] and [I+R]); two groups with saline instillation only ([saline+I] and [saline+I+R]); and four experimental groups with NAC (50 mg/kg), administered by instillation ([NAC+I], [NAC+I+R] and [I+NAC+R]) or by aerosol ([NACaero+I+R]). Cell counts and protein levels in bronchoalveolar lavage (BAL) were determined. RESULTS: NAC administered prior to hilar clamping led to a significant decrease in macrophages and lymphocytes and interleukin (IL)-1 beta levels after ischemia. NAC also resulted in significantly fewer macrophages, lymphocytes and neutrophils as well as IL-1 beta, keratinocyte cytokine (KC), monocyte chemoattractant protein (MCP)-1 and IL-6 levels in BAL taken after reperfusion. CONCLUSIONS: NAC treatment prior to warm ischemia attenuates inflammatory changes after both the ischemic and reperfusion periods.