Caroline Marie F Meers

Early Outcome After Lung Transplantation From Non–Heart-Beating Donors is Comparable to Heart-Beating Donors

BACKGROUND The use of non-heart-beating donors (NHBD) to overcome organ shortage is moving into the clinic. In 2007, 5 of 51 lung transplantations (LTx) in our center were performed with lungs from controlled NHBD. METHODS Our aim was to describe these 5 NHBD LTx recipients and compare early outcome (<or= 6 months) with a cohort of 10 heart-beating donor (HBD) LTx recipients matched for age, gender, underlying disease, and time of surgery. Clinical outcomes were assessed, including ischemic times, gas exchange, primary graft dysfunction, time to extubation, time of discharge from intensive care unit/hospital, and pulmonary function. Airway and systematic inflammation were evaluated by bronchoalveolar lavage, total and differential cell counts, and plasma C-reactive protein levels, respectively. RESULTS Early outcome in the NHBD group was comparable to the HBD group at the clinical and inflammatory level. The NHBD group showed a trend for earlier extubation (p = 0.054), greater increase in forced expiratory volume in 1 second (p = 0.054), and a significantly lower number of infections (p = 0.01). The NHBD group also had lower numbers of total cells (p = 0.04) and macrophages (p = 0.03) in bronchoalveolar lavage on day 21. CONCLUSIONS Outcome after LTx in NHBD recipients is not inferior to HBD recipients during the first 6 months. Late results and effect on chronic rejection should be further awaited. Controlled NHBD may offer a valid source of lungs to overcome organ shortage in LTx.

The number of lung transplants can be safely doubled using extended criteria donors; A single‐center review

Relaxing the standard lung donor criteria may significantly increase the reported 15% organ yield but post‐transplant recipient outcome should be carefully monitored. Charts from all consecutive deceased organ donors within our hospital network were reviewed over a 2‐year period. Reasons for lung refusals and number of lungs transplanted were analysed. Hospital outcome including early recipient survival was compared between standard‐ and extended criteria donors. Out of 283 referrals, 164 (58%) qualified as donor of any organ. The majority (65.9%) of these effective donors were declined for lung donation because of chest X‐ray abnormalities (20%), age >70 years (13%), poor oxygenation (10%), or aspiration (9%). Out of 56 (34.1%) accepted lung donors, 50 transplants were performed at our center, 23 from standard criteria donors versus 27 from extended criteria donors. There were no significant differences in hospital outcome and in early survival between lung recipients from both donor groups. Lung acceptance rate (34.1%) in our donor network is 10–20% higher than reported figures. The number of lung transplants in our center doubled by accepting extended criteria donors. This policy did not negatively influence our results after lung transplantation.

A Model of Ex Vivo Perfusion of Porcine Donor Lungs Injured by Gastric Aspiration: A Step Towards Pretransplant Reconditioning

BACKGROUND Evidence of aspiration remains a major reason for declining donor lungs contributing to current organ shortage. The aim of the present ex vivo lung perfusion (EVLP) study was to compare lungs injured by gastric juice (GJ) with normal lungs. METHODS Pigs (32.3 ± 11.2 kg) were divided into two groups. Study group [GJ; n = 6] was intratracheally instilled with GJ, while sham bronchoscopy was performed in control group [C; n = 6]. Graft function was assessed during EVLP for 2 h. Oxygenation, aerodynamic, and hemodynamic parameters were recorded every 30 min. Wet to dry weight ratio (W/D) was calculated. Bronchoalveolar lavage was performed. Tissue samples were collected. RESULTS Pulmonary vascular resistance was higher and pulmonary flow was lower in [GJ] versus [C] at T120; (P < 0.05). Mean airway pressure was higher in (P < 0.05) and compliance was lower (P < 0.001) in [GJ]. No differences in oxygenation were seen between groups. W/D of left lung in [GJ] after EVLP was slightly (P < 0.05) higher compared with the nonperfused right lung. More neutrophils were present in [GJ] before (P < 0.01) and after EVLP (P < 0.05). Histologic alterations were more prominent in [GJ], but did not worsen after EVLP. CONCLUSION EVLP of injured lungs is possible for 2 h despite increased edema. This model could help to investigate ways to repair caustic lung injury during EVLP.

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. At T0 bronchoalveolar lavage (BAL) was performed followed by instillation of 4 mL/kg GJ or saline solution (SAL). Hemodynamics, aerodynamics and oxygenation were recorded for two hours. Serum samples were collected. At T120 a second BAL was performed. CT scans of explanted, inflated lungs were taken, tissue samples were collected and wet/dry weight ratio (W/D) was calculated. Pepsin and bile acids were measured in BAL. IL-8, CRP and MMP-9 were measured in serum and in BAL. RESULT Oxygenation and lung compliance was lower in [GJ] versus [SAL] (P < 0.01 and P < 0.001, respectively). More consolidation areas were noticed on CT in GJ versus SAL (P < 0.01). Hemorrhage, edema and neutrophil inflammation were seen on histology in [GJ] (P < 0.01, P < 0.001, P < 0.001, respectively). BAL neutrophils, pepsin, bile acids, and IL-8 (P < 0.05) increased in [GJ]. W/D was higher in [GJ] versus SAL (P < 0.001). CONCLUSION Instillation of GJ in pig lungs caused acute lung injury with impaired oxygenation and increased inflammation in BAL, on histology, and on imaging. This model holds promise to assess the efficacy of a broad range of treatment strategies including ex vivo lung perfusion (EVLP).

Change in Donor Profile Influenced the Percentage of Organs Transplanted From Multiple Organ Donors

We hypothesized that the change in donor profile over the years influenced the percentage of transplantations. We reviewed medical records for all multiple-organ donors (MODs) within our network. The percentage of transplanted organs was compared between 1991-1992 (A) and 2006-2007 (B). In period A, 156 potential MODs were identified compared with 278 in period B. Fifteen potential donors (10%) in period A and 114 (41%) in period B were rejected because they were medically not suitable (40% vs 75%) or there was no family consent (60% vs 25%). Of the remaining effective MODs (141 in period A and 164 in period B), mean (standard deviation = SD) age was 34 (5) years vs 49 (17) years (P < .001). Brain death resulted from craniocerebral trauma in 69% vs 39%, cerebrovascular disease in 24% vs 46%, hypoxia in 4% vs 15%, and brain tumor in 2% vs 0.6% (P < .001). Chest trauma was present in 19% vs 9% (P < .01). The percentage of MODs who received mechanical ventilation for more than 5 days was 8% vs 24% (P < .001). The percentage of organs transplanted in periods A vs B was kidneys, 97% vs 79%; livers, 64% vs 85%; hearts, 60% vs 26%; lungs, 7% vs 35%; and pancreas, 6% vs 13% (P < .001). The number of referred potential MODs increased by 80%, resulting in a small increase in effective MOD organs (17%), mainly because of medical contraindications. The MOD profile changed to older age, fewer traumatic brain deaths, and longer ventilation time. We transplanted more livers, lungs, and pancreases but fewer kidneys and hearts.

Preemptive therapy with steroids but not macrolides improves gas exchange in caustic-injured donor lungs.

BACKGROUND Donor lungs are susceptible to aspiration in the period before and after brain death. We hypothesized that preemptive anti-inflammatory treatment may result in better graft performance as evaluated during ex vivo lung perfusion (EVLP). METHODS Pigs (27.4 ± 8.3kg) were divided into four groups (n = 6). Group [S] was treated with steroids (methylprednisolone 10 mg/kg), group [M] with macrolides (clarithromycin 250 mg), and group [P] with placebo (saline). In all groups, treatment was given i.v. 25, 18, and 1 h before instillation of 4 mL/kg gastric juice (GJ). Group [C] without GJ instillation served as a control group. Two hours after the onset of acute lung injury, lungs were flushed, explanted, and stored cold for 75 min. Graft performance was then assessed during EVLP for 2 h. Aerodynamic and hemodynamic parameters and oxygenation capacity (∆PO(2)) were recorded every 30 min (T30-T120). BAL samples were collected and analyzed for total and differential cells, IL-6, IL-1β, 8- isoprostane, and CRP levels. Wet-to-dry weight ratio [W/D] was measured and tissue samples were collected for histology. RESULTS ΔPO(2) in [S] was comparable to [C] and was higher versus [M] (P < 0.05) and [P] (P < 0.01). No differences were observed in pulmonary vascular resistance, lung compliance, and mean airway pressure. No additional edema was noticed after 2 h of EVLP. Cellular and biomolecular changes in BAL fluid and histologic alterations were comparable among the three study groups. CONCLUSION Preemptive treatment of donors with steroids but not macrolides improves gas exchange in a porcine lung injury model independently from its anti-inflammatory activity.

The need for a new animal model for chronic rejection after lung transplantation.

The single most important cause of late mortality after lung transplantation is obliterative bronchiolitis (OB), clinically characterized by a decrease in lung function and morphologically by characteristic changes. Recently, new insights into its pathogenesis have been acquired: risk factors have been identified and the use of azithromycin showed a dichotomy with at least 2 different phenotypes of bronchiolitis obliterans syndrome (BOS). It is clear that a good animal model is indispensable to further dissect and unravel the pathogenesis of BOS. Many animal models have been developed to study BOS but, so far, none of these models truly mimics the human situation. Looking at the definition of BOS, a good animal model implies histological OB lesions, possibility to measure lung function, and airway inflammation. This review sought to discuss, including pros and cons, all potential animal models that have been developed to study OB/BOS. It has become clear that a new animal model is needed; recent developments using an orthotopic mouse lung transplantation model may offer the answer because it mimics the human situation. The genetic variants among this species may open new perspectives for research into the pathogenesis of OB/BOS.

A Porcine Model to Study Ex Vivo Reconditioning of Injured Donor Lungs

BACKGROUND Brain death rapidly results in lung injury making many cadaveric donors unsuitable for lung transplantation. The aim of this study was to develop a porcine model of lung injury as a first step to study mechanisms to ameliorate the pretransplant graft quality during ex vivo perfusion. MATERIALS AND METHODS Male pigs (47 ± 8 kg) were divided into three groups: LPS-group [LPS] (n = 6) [instillation of lipopolysaccharides (15 mg/lung)]; saline-group [SAL] (n = 5) (50 mL saline/lung); and sham-group [SHAM] (n = 5). CT scans of the lungs were taken 17h before (T-17) and 31h after (T31) instillation. Broncho-alveolar lavage (BAL) was performed, and blood gases, hemodynamic, and aerodynamic parameters were measured at T 0 and T 50. Blood samples and temperature were taken at all time points. Pigs were sacrificed during cold pulmoplegia (T 50), and tissue samples were collected for histology. Wet lung weight was measured. RESULTS Wet lung weight/body weight was higher in [LPS] versus [SAL] (P < 0.05). Total BAL cells were higher in [LPS] versus [SAL] and [SHAM] at T 50 (left: P < 0.001 and P < 0.01; right: P < 0.01 and P < 0.001). More neutrophils were present in BAL of [LPS] at T 50 versus T 0 (left: P < 0.001; right: P < 0.01). [LPS] demonstrated more ground glass opacities (GGO) on CT at T 31 compared with [SAL] and [SHAM] (P < 0.05). Histologically, more interstitial hemorrhage was observed in [LPS] versus [SAL] and [SHAM](P < 0.01). Neutrophils in blood increased and lymphocytes decreased in [LPS] versus [SAL] (P < 0.05). No differences were observed in hemodynamic and aerodynamic parameters and in saturation between groups at T 50. CONCLUSIONS LPS instillation caused inflammation with more cells in BAL, changes on CT, and histology. However, no physiologic changes occurred.