Donor Lungs For Transplantation Research Articles

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

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. Mice were divided in 7 groups (n = 6/group). In 3 groups, ischemia was induced by clamping the hilum of the left lung for 30, 60 or 90 minutes (Groups [30I], [60I] or [90I], respectively). In 3 more groups, the lung was reperfused for 4 hours after identical ischemic intervals (Groups [30I+R], [60I+R] or [90I+R], respectively). Surgical impact was evaluated in a sham group ([sham]). Total and differential cell counts and interleukin-1beta (IL-1beta) protein levels in bronchoalveolar lavage (BAL) were determined and their correlations were investigated. Total cell, macrophage and lymphocyte numbers and IL-1beta protein levels increased progressively with longer ischemic intervals. A significant rise in BAL macrophages and lymphocytes was observed between [60I] and [90I] (p < 0.01 and p < 0.001, respectively). BAL neutrophils only increased after reperfusion with longer ischemic intervals. A positive correlation was found in the ischemic groups between IL-1beta levels and the number of macrophages (r = 0.62; p = 0.0012) and the number of lymphocytes (r = 0.68; p = 0.0002). A positive correlation was found in the reperfusion groups between IL-1beta levels and the number of neutrophils (r = 0.48; p = 0.044). This study demonstrates for the first time that BAL macrophages and lymphocytes increase significantly during warm ischemia and correlate with IL-1beta levels.

A Report of the Vancouver Forum on the Care of the Live Organ Donor: Lung, Liver, Pancreas, and Intestine Data and Medical Guidelines

An international conference of transplant physicians, surgeons, and allied health professionals was held in Vancouver, Canada, on September 15 and 16, 2005 to address the care of the live lung, liver, pancreas, and intestine organ donor. The Vancouver Forum was convened under the auspices of the Ethics Committee of The Transplantation Society. Forum participants included over 100 leaders in organ transplantation, representing many countries from around the world, including participants from the following continents: Africa, Asia, Australia, Europe, North and South America. The objective of the Vancouver Forum was to develop an international standard of care for the live lung, liver, pancreas and intestinal organ donor. This Vancouver Forum followed a conference convened in Amsterdam on the care of the live kidney donor (1, 2). There were four organ specific work groups at the Vancouver Forum: lung, liver, pancreas and intestine. Each organ work group addressed the following topics in concert and reported their findings in a plenary presentation to all participants:

Evaluation of Techniques for Lung Transplantation Following Donation After Cardiac Death

Lung transplantation using "donation after cardiac death" donors is a potential means to alleviate the shortage of suitable donor lungs for transplantation, but the practicality and utility of the various possible techniques need to be clarified. Using a dog model, we explored seven variations of standoff (ischemic) time (50 to 240 minutes), topical cooling (60 to 120 minutes), and flush cooling and cold storage (30 to 140 minutes) to mimic different human donor lung retrieval scenarios that can follow donation after cardiac death. The functional status of donation after cardiac death donor lungs was assessed initially with a 250 mL pulmonary arterial blood flush while ventilating with 100% oxygen and then on an ex-vivo perfusion rig for 120 minutes after retrieval. All lungs achieved an excellent pO2/FiO2 ratio ranging from 472 to 586 with stable pulmonary artery pressures and pulmonary vascular resistance and no net weight gain (952 +/- 221 g versus 1,006 +/- 235 g) during the 120-minute evaluation period. Initial blood flush correlated well with measured perfusion rig pO2 at 30 minutes (R2 = 0.63). This canine study suggests that lungs donated after cardiac death are reproducibly useable for transplantation with ischemic times of as long as 60 minutes. Although more study is needed, a blood flush evaluation is simple and may have a role as a secondary allograft assessment tool. The existing techniques of donor lung evaluation and preservation after donation following cardiac death thus appear both feasible and practical.

Extended donor criteria in lung transplantation: Impact on organ allocation

Some reports have documented a higher early mortality with the use of extended criteria donors in lung transplantation. None have evaluated how outcomes compare with the use of these organs for single and bilateral transplantation or whether this practice results in a higher incidence of early bronchiolitis obliterans syndrome. We performed a retrospective review of case notes, intensive therapy unit database, and donor details. Between January 1, 2000, and December 31, 2004, 201 patients underwent lung or heart-lung transplantation. Eighty-three (41.3%) patients received organs deemed marginal on the basis of at least one of the following criteria: donor age greater than 55 years, duration of ventilation greater than 5 days, purulent secretions or inflammation at bronchoscopy, smoking of 20 or more cigarettes per day, abnormality on chest roentgenogram, or PO2/fraction of inspired oxygen ratio of less than 300 mm Hg immediately before donor organ procurement. Recipients of marginal lungs had a higher incidence of severe (grade 3) primary graft dysfunction (43.9% vs 27.4%, P = .015) and 90-day organ-specific mortality (15.7% vs 5.1%, P = .012). Bilateral transplantation carried a significantly higher 30-day mortality if performed with marginal organs (17.0% vs 2.7% with standard donor organs, P = .005). Thirty-day mortality was not significantly different for the transplantation of single marginal or standard donor lungs. Cumulative survival and survival free of bronchiolitis obliterans syndrome was not affected by marginal donor status. Transplantation of extended criteria donor lungs leads to a higher incidence of primary graft dysfunction. Bilateral transplantation with these organs seems to confer less reserve, resulting in a higher early mortality rate. Medium-term functional outcome is, however, not adversely affected by the relaxation of donor criteria.

Two Successful Lung Transplantations From a Dialysis-Dependent Donor

The shortage of organs for lung transplantation has led to the growing use of "marginal" donors. Although patients on hemodialysis are still excluded as lung transplant donors because of the possible effects of renal failure on the lungs, recent data suggest that they may be suitable in selected cases. This article describes the successful transplantation of two lungs from a single donor who had been receiving long-term hemodialysis treatment. In the absence of other causes of pulmonary diseases, such as smoking or lung infection, lungs from dialysis-dependent patients may be acceptable for lung transplantation.

Peripheral Lung Volume Reduction Improved Early Graft Function in Severe Size Mismatched Living Donor Lobar Lung Transplantation

Background Lung transplantation from adults to infants or small children is still challenging because of concerns related to size disparity. Peripheral lung volume reduction for size disparity in cadaveric donor lung transplantation has been widely performed; however, little is known about the efficacy and the functional outcomes of downsizing the implanted lobes for severe size disparity in living donor lobar lung transplantation. Methods Thirteen size-mismatched (donor/recipient lung volume ratio >2.82) bilateral living donor lobar lung transplants were performed with (reduction group, n = 6) or without (no-reduction group, n = 7) peripheral lung volume reduction. Results On spontaneous respiration, PaO 2 in the reduction group was significantly higher than that in the no-reduction group ( P < .01) and PaCO 2 in the reduction group was significantly lower than that in the no-reduction group ( P < .001). Pulmonary vascular resistance in the reduction group remained significantly lower than that in the no-reduction group throughout the assessment periods after chest closure ( P < .05). Peak airway pressure in the no-reduction group increased significantly at the time of chest closure ( P < .001) and remained significantly higher than that in the reduction group throughout the assessment period on mechanical ventilation ( P < .01). The percentage of weight reduced from implanted grafts significantly correlated with donor/recipient lung volume ratio ( r = 0.82, P < .05). Conclusions Peripheral lung volume reduction is useful to improve early graft function in severe size mismatched experimental living donor lobar lung transplantation. The technique might allow for further flexibility in donor size and for increasing the donor pool for small recipients.

Lung transplantation: donor and recipient critical care aspects

The purpose of this paper is to highlight new developments in donor and recipient lung transplant issues for the critical care physician. A shortage of suitable lung donors has led to the use of extended donors and the development of novel techniques such as live-donor lung transplantation and the use of non-heart-beating donors. The increased experience and success with lung transplantation has also resulted in the extension of this therapy to patients previously considered unsuitable for transplantation. Postoperative outcomes can be affected by many of these recent donor and recipient changes. Improved preservation solutions and techniques to reduce reperfusion injury may be able to ameliorate some of the new perioperative graft dysfunction, but morbidity is still potentially significant, and extraordinary interventions such as extracorporeal membrane oxygenation may be required in selected cases. Patients undergoing lung transplantation continue to be very challenging in the intensive care unit. A multidisciplinary approach to care, and early recognition of serious problems, will help improve outcomes.

Influence of Donor Characteristics on Outcome After Lung Transplantation: A Multicenter Study

The liberalization of lung-donor criteria and the use of marginal donors have been advocated to face the current shortage of donors in lung transplantation. However, the impact of donor characteristics on the outcome of lung transplantation is still largely unknown. We aimed to determine, on a large cohort of patients, the effect of donors characteristics on short- and long-term outcome of lung transplantation Between 1988 and 1998, a total of 785 adult patients underwent single-lung transplantation (n = 270), bilateral-lung transplantation (n = 251), and heart-lung transplantation (n = 264) in 7 centers in France. We constructed several multivariate models to assess the relationship between donor characteristics and early gas exchange, duration of mechanical ventilation, and long-term survival after lung transplantation. Among donor characteristics, donor gas exchange before harvest was found to be significantly associated with recipient early gas exchange, duration of mechanical ventilation, and long-term survival after adjustment for potential confounding variables. Moreover, nonlinear modeling showed a steep increase in the relative risk of death when donor PaO2/FiO2 before harvest was below 350 (hazard ratio 1.43; 95% confidence interval 1.10-1.85; p = 0.01). Donor and recipient sex mismatch were also found to be significantly associated with long-term survival. Although liberalization of lung-donor criteria may be considered to overcome the shortage of lung donors, our data suggest that the violation of the gas-exchange criterion should be avoided.

Improving the number and condition of donor lungs for transplantation*

Improving the number and condition of donor lungs for transplantation*

From research to reality: Development of a clinical Non Heart Beating Donor (NHBD) Lung Transplant (LTx) program

ischemic function of Perfadex-protected allografts was evaluated. Methods: In group 1, five pig lungs, each, were preserved with Perfadex solution (PER) and stored for 27 hours. In group 2, 100 g of Iloprost were aerosolized over 30 minutes using a novel mobile ultrasonic nebulizer (Optineb®) prior to identical organ harvest (PER-ILO). Following left lung transplantation and contralateral lung exclusion, hemodynamics, pO2/FiO2 and dynamic compliance were monitored for 6 hours and compared to sham-operated controls. Pulmonary edema was determined stereologically and by wet-to-dry ratio (W/D). Statistics comprised ANOVA analysis with repeated measures. Results: Dynamic compliance and PVR were superior in Ilomedintreated animals as compared to untreated organs (p 0.05), while oxygenation was comparable between groups. Wet-to-dry lung weight ratio revealed a significantly lower amount of lung water in PER-ILO organs (p 0.048), while stereology showed a trend towards less intraalveolar edema. Conclusions: Endobronchial application of Iloprost in donor lungs prior to Perfadex preservation decreases postischemic edema and significantly improves lung compliance and vascular resistance. This innovative approach is easily applicable in the clinical setting and offers a new strategy for improvement of pulmonary allograft preservation.

3D-Multidetector CT Angiography in the Evaluation of Potential Donors for Living Donor Lung Transplantation

In living donor lung transplant, donor lobectomies from 2 donors provide right and left lower lobes for transplantation. In the past, routine evaluation of pulmonary anatomy was not performed preoperatively. Intraoperatively, surgeons were often forced to sacrifice the lingular artery or right middle lobe segmental artery to obtain an adequate arterial cuff for safe reimplantation. This study was performed to evaluate the utility of preoperative 3D-multidetector CT angiography (3D-MDCTA) as a noninvasive method of assessing pulmonary arteries to improve donor selection and surgical planning for living lung donors. Five potential lung donors for 2 recipients were included in the study. CT scanning with 4 channel multidetector-row CT was performed, using a modified pulmonary embolism protocol. Post-processing was performed using volume rendering techniques on a commercially available workstation. 3D-MDCT demonstrated that there are a number of variations in pulmonary arterial anatomy and that ideal anatomy was seldom encountered. Comparison of different donors determined which lower lobes were most favorable for transplantation. Surgery confirmed the accuracy of 3D-MDCTA. There were no pulmonary arterial complications, and no vessels were sacrificed. Safely explanting lower lobes from living donors for lung transplantation poses challenges not encountered in harvesting cadaveric donors or performing lobectomies for malignancy. 3D-MDCTA of pulmonary arteries can noninvasively delineate the often-complex pulmonary anatomy, which may assist in donor selection as well as reduce donor intraoperative and postoperative vascular complications.

Recurrence of alpha 1-antitrypsin deficiency emphysema on Computed Tomography (CT) after lung transplantation

Alpha 1-antitrypsin (AAT) is secreted mainly by hepatocytes but also macrophages, intestinal and bronchial epithelial cells. AAT deficiency (AATD) from Chromosome 14q mutations predisposes to pan-acinar emphysema mainly of the lower lobes. After a lung transplant donor cells should produce AAT, however it has been shown that broncho-alveolar lavage fluid from lung transplants for AATD emphysema lacks AAT during respiratory infections. We report the novel finding of CT recurrence of emphysema in lung transplants for AATD.

Paediatric lung transplantation

Since 1990, lung transplantation has been performed in infants, children and adolescents in small numbers, and the numbers, in comparison with adult transplants, remain small today. The indications for lung transplantation are similar in childhood when compared with adults, but the disease entities are distinct. In children, severe pulmonary vascular disease is most commonly associated with developmental abnormalities or congenital heart disease, as opposed to idiopathic pulmonary hypertension. Cystic fibrosis is the dominant indication for lung transplantation in older childhood and adolescence. The operative approach to lung transplantation in early life differs from that in adults, in that cardiopulmonary bypass is more likely to be utilised and bilateral lung transplantation is strongly preferred to single lung transplantation. Living donor lung transplantation is proportionately more common in children and adolescents than in adults. Post-transplant complications related to viral infection and post-transplant lymphoproliferative disease are more common and more likely to be severe and life-threatening. Bronchiolitis obliterans is the most important complication after paediatric lung transplantation and limits both the quality of life and duration of survival, as in adults.

Fungal infections

Fungal infections

Lung transplantation in Japan.

The first successful living-donor lobar lung transplant (LDLLT) in Japan was performed at Okayama University in October 1998 after a long period of waiting for the legalization of thoracic organ transplantation. By May 2003, a further 41 lung transplants had been performed; 28 from living donors and 13 from cadaveric donors. The indications for a lung transplant are very specialized in Japan, the most common being primary pulmonary hypertension. Although the number of lung transplants is still small, survival in Japan, at 72% after 4 years, is better than the world average. Because the number of available cadaveric donors for lung transplantation is limited, at less than 5 per year, LDLLT is a realistic option for properly selected candidates.

Organ donation and transplantation trends in the USA, 2003

This summary provides an overview of solid organ transplantation in the USA, produced as part of the 2003 OPTN/SRTR Annual Report. The Annual Report is prepared by the Scientific Registry of Transplant Recipients (SRTR) in collaboration with the Organ Procurement and Transplantation Network (OPTN) under contract with the Health Resources and Services Administration (HRSA). A wide range of activities related to solid organ transplantation in the USA are thoughtfully addressed in this publication with the intention of providing useful information to patients, the transplant community, the public, and the Federal Government.

Impact of an innovative preservation strategy on the use of non-heart-beating donors in experimental pig lung transplantation

Objectives: Lung transplantation is limited by severe scarcity of donor organs. Currently, aside from living-related lobar donors, grafts are retrieved from brain-dead heart beating donors. To potentially expand the donor pool, lung retrieval from non-heart-beating donors (NHBD) has been reported recently. However, no NHBD studies exist using the novel approach of retrograde lung preservation with Perfadex solution.

Transplantation in Canada: report of the Canadian Organ Replacement Register

The solid organ transplant rate in Canada grew from 49.5 per million population (PMP) in 1993 to 56.8 PMP in 2002, with a peak rate of 61.0 in 2000. Most of this increase was seen in living donor kidney, liver, and lung transplants where combined rates rose twofold, from 124.9 per 1000 transplants to 243.5. Despite this, the rate of organ transplantation in the United States was 150% that of Canada in 2002. As of December 31, 2002, there were 3956 patients waiting for an organ transplant in Canada, an 84% increase in the total number of patients on the waiting list as of December 31, 1993, 10 years ago. Cadaveric organ donation did not change over this period. An international comparison of cadaveric organ donation rates for 2001 place Canada (13.5 PMP) well below Spain (32.5 PMP) and the United States (22.6 PMP) but above Australia (9.3 PMP). As a result the annual gap between transplants performed and the waiting list has grown from 927 in 1992 to 2230 in 2001, representing an annual increase of 8.3%.

Regulation and oversight of adult living donor liver transplantation.

Key points 1. Ethical principles and informed consent standards should be implemented for all living donors. 2. Institutions that perform living donor transplantation should provide an independent donor advocate to ensure that informed consent standards and ethical principles are applied to the practice of all live organ donor transplantation. 3. A database of health outcomes for all live donors should be established and funded through and under the auspices of the US Department of Health and Human Services. 4. Serious consideration should be given to the establishment of a separate resource center for living donors and their families. 5. The present preference in Organ Procurement and Transplantation Network allocation policy, given to previous living organ donors who subsequently need a kidney, should be extended so that any living organ donor would be given preference as a candidate for any organ transplant, should one become needed. .6. A process should be established to verify qualifications of a center to perform living donor liver or lung transplantation.

In-situ topical cooling of lung grafts: early graft function and surfactant analysis in a porcine single lung transplant model.

Improvement of organ preservation is essential to facilitate acceptance of marginal donor lungs for transplantation. Thus, recruiting non-heart-beating donors (NHBD) may be one reasonable strategy to augment the organ-pool especially in the field of pulmonary transplantation. Topical cooling (TC) of donor lungs could provide fast organ-protection and is an available procedure even in smaller centers. In this study transplanted lung function and surfactant activity in same lungs, which were preserved by TC, were assessed following transplantation. Twelve porcine allogeneic single lung transplants were performed. Six lungs that were flush preserved through the antegrade route served as controls. The other six lungs were preserved by TC for 30 min after induction of cardiac arrest by repeated application of cold saline (8 degrees C) to both pleural cavities. Lungs of both groups were stored in LPD solution for 24 h at 8 degrees C. After transplantation, the recipient's right bronchus and right pulmonary artery were clamped. Major endpoints included early graft function over a period of 7 h. Hemodynamic measures and respiratory functions were recorded in 30-min intervals. Surfactant function was determined before transplantation and 2 h after reperfusion by broncho-alveolar lavage fluid analysis. Only four animals of the control-group survived the 7 h reperfusion period. Right heart failure occurred in two animals after 150 and 240 min of reperfusion. All six animals in the TC group survived the observation period. Pulmonary vascular resistance (p<0.01), pulmonary artery pressure (p=0.03), and lung tissue water content remained significantly lower in topically cooled allografts (p=0.01) vs. controls. Surfactant function after transplantation was comparable in both groups with a trend towards lower protein contents (p=0.07) in the broncho-alveolar fluid of grafts after TC. In-situ TC seems to be a reliable strategy to preserve lungs for up to 24 h. It even surpasses the results of LPD-perfused grafts in hemodynamic function and survival time.