In the last 20 years, lung transplantation has become the standard treatment for patients with end-stage lung disease. However, less than 20% of the donor lungs available for transplant are actually usable. This disparity between the growing number of recipients and the small number of donors has resulted in increased mortality among lung transplant candidates on waiting lists. Strategies such as the utilization of organs from marginal donors have proven ineffective in increasing the number of transplants. In 2000, a new method for reconditioning human lungs that had been previously rejected for transplantation was developed in Sweden. We describe our initial experience with ex vivo lung perfusion.

Keywords: Lung transplantation; Organ preservation; Organ preservation solutions; Thoracic surgery.

Objective: To evaluate the use of ex vivo lung perfusion (EVLP) clinically to prepare donor lungs for transplantation. Methods: A prospective study involving EVLP for the reconditioning of extended-criteria donor lungs, the criteria for which include aspects such as a PaO2/FiO2 ratio < 300 mmHg. Between February of 2013 and February of 2014, the lungs of five donors were submitted to EVLP for up to 4 h each. During EVLP, respiratory mechanics were continuously evaluated. Once every hour during the procedure, samples of the perfusate were collected and the function of the lungs was evaluated. Results: The mean PaO2 of the recovered lungs was 262.9 ± 119.7 mmHg at baseline, compared with 357.0 ± 108.5 mmHg after 3 h of EVLP. The mean oxygenation capacity of the lungs improved slightly over the first 3 h of EVLP-246.1 ± 35.1, 257.9 ± 48.9, and 288.8 ± 120.5 mmHg after 1, 2, and 3 h, respectively-without significant differences among the time points (p = 0.508). The mean static compliance was 63.0 ± 18.7 mmHg, 75.6 ± 25.4 mmHg, and 70.4 ± 28.0 mmHg after 1, 2, and 3 h, respectively, with a significant improvement from hour 1 to hour 2 (p = 0.029) but not from hour 2 to hour 3 (p = 0.059). Pulmonary vascular resistance remained stable during EVLP, with no differences among time points (p = 0.284). Conclusions: Although the lungs evaluated remained under physiological conditions, the EVLP protocol did not effectively improve lung function, thus precluding transplantation.

Keywords: Lung transplantation; Organ preservation; Brain death; Donor selection.

Since they were first established, ex vivo models of lung reconditioning have been evaluated extensively. When rejected donor lungs are used, the great variability among the cases can hinder the progress of such studies. In order to avoid this problem, we developed a technique that consists of separating the lung block into right and left blocks and subsequently reconnecting those two blocks. This technique allows us to have one study lung and one control lung.

Keywords: Lung transplantation; Transplantation conditioning; Organ preservation; Organ preservation solutions.

Lung transplantation has come to be viewed as the best treatment option for various end-stage lung diseases. The low number of viable donors continues to be a major obstacle to increasing the number of lung transplants, resulting in high mortality among patients on the waiting list. Unlike transplantation of other solid organs, lung transplantation is primarily limited not by the absolute number of donors but by the viability of the donor lungs, which can be damaged by brain death and by treatments given in the ICU. There are various proposals of ways to increase the number of lung donors: intensification of donation campaigns, use of non-heart-beating donors, living lobar lung transplantation, and adoption of more flexible criteria for donors. However, the proposal that has attracted the most attention from lung transplant groups is ex vivo lung perfusion, especially due to the prospect of reconditioning previously discarded lungs. This system consists of perfusion and ventilation of the isolated heart-lung block using a modified cardiopulmonary bypass circuit. Various authors have been studying this technique due to the satisfactory results obtained and the prospect of an increase in the number of organs suitable for transplantation. Researchers in Sweden, Canada, Austria, England, Spain, and Brazil have extensive experience with the method and have introduced modifications to it. The objective of this article was to review the development of, state of the art in, and future prospects for the ex vivo model of lung perfusion and reconditioning.

Keywords: Lung transplantation; Transplantation conditioning; Perfusion; Organ preservation.

Objective: To present a model of prostaglandin I2 (PGI2) administration (inhaled vs. parenteral) and to assess the functional performance of the lungs in an ex vivo lung perfusion system. Methods: Forty Wistar rats were anesthetized and placed on mechanical ventilation followed by median sterno-laparotomy and anticoagulation. The main pulmonary artery was cannulated. All animals were maintained on mechanical ventilation and were randomized into four groups (10 rats/group): inhaled saline (IS); parenteral saline (PS); inhaled PGI2 (IPGI2); and parenteral PGI2 (PPGI2). The dose of PGI2 used in the IPGI2 and PPGI2 groups was 20 and 10 µg/kg, respectively. The heart-lung blocks were submitted to antegrade perfusion with a low potassium and dextran solution via the pulmonary artery, followed by en bloc extraction and storage at 4°C for 6 h. The heart-lung blocks were then ventilated and perfused in an ex vivo lung perfusion system for 50 min. Respiratory mechanics, hemodynamics, and gas exchange were assessed. Results: Mean pulmonary artery pressure following nebulization decreased in all groups (p < 0.001), with no significant differences among the groups. During the ex vivo perfusion, respiratory mechanics did not differ among the groups, although relative oxygenation capacity decreased significantly in the IS and PS groups (p = 0.04), whereas mean pulmonary artery pressure increased significantly in the IS group. Conclusions: The experimental model of inhaled PGI2 administration during lung extraction is feasible and reliable. During reperfusion, hemodynamics and gas exchange trended toward better performance with the use of PGI2 than that with the use of saline.

Keywords: Prostaglandins; Lung transplantation; Reperfusion; Models, animal; Rats.

Objective: To compare histopathological findings and the degree of apoptosis among rat lungs preserved with low-potassium dextran (LPD) solution, histidine-tryptophan-ketoglutarate (HTK) solution, or normal saline (NS) at two ischemia periods (6 h and 12 h) using an experimental rat model of ex vivo lung perfusion. Methods: Sixty Wistar rats were anesthetized, randomized, and submitted to antegrade perfusion via pulmonary artery with one of the preservation solutions. Following en bloc extraction, the heart-lung blocks were preserved for 6 h or 12 h at 4°C and then reperfused with homologous blood for 60 min in an ex vivo lung perfusion system. At the end of the reperfusion, fragments of the middle lobe were extracted and processed for histopathological examination. The parameters evaluated were congestion, alveolar edema, alveolar hemorrhage, inflammatory infiltrate, and interstitial infiltrate. The degree of apoptosis was assessed using the TdT-mediated dUTP nick end labeling method. Results: The histopathological examination showed that all of the lungs preserved with NS presented alveolar edema after 12 h of ischemia. There were no statistically significant differences among the groups in terms of the degree of apoptosis. Conclusions: In this study, the histopathological and apoptosis findings were similar with the use of either LPD or HTK solutions, whereas the occurrence of edema was significantly more common with the use of NS.

Keywords: : Organ preservation; Organ preservation solutions; Lung transplantation; Reperfusion injury; Apoptosis.

Objective: The shortage of viable lungs is still a major obstacle for transplantation. Trauma victims who represent potential lung donors commonly present hypovolemic shock leading to pulmonary inflammation and deterioration and rejection after transplantation. Seeking to improve lung graft, new approaches to donor treatment have been tested. This study focuses on treatment with mesenchymal stem cells (MSCs) or soluble factors produced by MSCs (FS-MSC) using a rat model for lung donors after hemorrhagic shock. Methods: Forty-eight rats were divided into four groups: Sham (n=12), animals without induction of hypovolemic shock; Shock (n=12), animals submitted to hypovolemic shock (mean arterial pressure 40 mmHg); MSC (n=12), animals submitted to hypovolemic shock and treated with MSCs, and FS (n=12), animals submitted to hypovolemic shock and treated with FS-MSC. The animals were subjected to a 50-minute hypovolemic shock (40 mmHg) procedure. The treated animals were monitored for 115 minutes. We performed histopathology of lung tissue and quantification of inflammatory markers (TNF-a, IL-1ß, IL-6, IL-10, iCAM and vCAM) in lung tissue and peripheral blood leukocytes (PBLs). Results: Hemorrhagic shock resulted in higher PBLs and neutrophil infiltrate in the lungs. FS animals had lower neutrophil density comparing with Shock and MSC animals (p<0.001). No differences in the cytokine levels in lung tissue were observed between the groups. Conclusions: The lungs of rats submitted to hemorrhagic shock and treated with FS-MSC showed reduced inflammation indicated in a decrease in lung neutrophil infiltrate.

Keywords: Lung transplantation; Tissue donors; Hypovolemic shock; Mesenchymal cells; Inflammation.