Flávio Guimarães Fernandes

Histologic and functional evaluation of lungs reconditioned by ex vivo lung perfusion

BACKGROUND Only about 15% of donor lungs are considered suitable for transplantation (LTx). Ex vivo lung perfusion (EVLP) has been developed as a method to reassess and repair damaged lungs. We report our experience with EVLP in non-acceptable donor lungs and evaluate its ability to recondition these lungs. METHODS We studied lungs from 16 brain-dead donors rejected for LTx. After harvesting, the lungs were stored at 4°C for 10 hours and subjected to normothermic EVLP with Steen Solution (Vitrolife, Göteborg, Sweden) for 60 minutes. For functional evaluation, the following variables were assessed: partial pressure of arterial oxygen (Pao(2)), pulmonary vascular resistance (PVR), and lung compliance (LC). For histologic assessment, lung biopsy was done before harvest and after EVLP. Tissue samples were examined under light microscopy. To detect and quantify apoptosis, terminal deoxynucleotide transferase-mediated deoxy uridine triphosphate nick-end labeling assay was used. RESULTS Thirteen lung donors were refused for having impaired lung function. The mean Pao(2) obtained in the organ donor at the referring hospital was 193.7 mm Hg and rose to 489 mm Hg after EVLP. During EVLP, the mean PVR was 652.5 dynes/sec/cm(5) and the mean LC was 48 ml/cm H(2)O. There was no significant difference between the mean Lung Injury Score before harvest and after EVLP. There was a trend toward a reduction in the median number of apoptotic cells after EVLP. CONCLUSIONS EVLP improved lung function (oxygenation capacity) of organs considered unsuitable for transplantation. Lung tissue structure did not deteriorate even after 1 hour of normothermic perfusion.

Perfusão pulmonar ex vivo: experiência nacional inicial

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.

Comparison of lung preservation solutions in human lungs using an ex vivo lung perfusion experimental model

OBJECTIVE: Experimental studies on lung preservation have always been performed using animal models. We present ex vivo lung perfusion as a new model for the study of lung preservation. Using human lungs instead of animal models may bring the results of experimental studies closer to what could be expected in clinical practice. METHOD: Brain-dead donors whose lungs had been declined by transplantation teams were used. The cases were randomized into two groups. In Group 1, Perfadex® was used for pulmonary preservation, and in Group 2, LPDnac, a solution manufactured in Brazil, was used. An ex vivo lung perfusion system was used, and the lungs were ventilated and perfused after 10 hours of cold ischemia. The extent of ischemic-reperfusion injury was measured using functional and histological parameters. RESULTS: After reperfusion, the mean oxygenation capacity was 405.3 mmHg in Group 1 and 406.0 mmHg in Group 2 (p = 0.98). The mean pulmonary vascular resistance values were 697.6 and 378.3 dyn·s·cm-5, respectively (p = 0.035). The mean pulmonary compliance was 46.8 cm H2O in Group 1 and 49.3 ml/cm H2O in Group 2 (p = 0.816). The mean wet/dry weight ratios were 2.06 and 2.02, respectively (p = 0.87). The mean Lung Injury Scores for the biopsy performed after reperfusion were 4.37 and 4.37 in Groups 1 and 2, respectively (p = 1.0), and the apoptotic cell counts were 118.75/mm2 and 137.50/mm2, respectively (p = 0.71). CONCLUSION: The locally produced preservation solution proved to be as good as Perfadex®. The clinical use of LPDnac may reduce costs in our centers. Therefore, it is important to develop new models to study lung preservation.

Modelo experimental ex vivo com bloco pulmonar dividido

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.

Cardiothoracic Surgery League from University of São Paulo Medical School: twelve years in medical education experience

INTRODUCTION Academic Leagues (Academic Interest Group) are entities that belong to medical schools and their hospitals. Their goals are research, medical education and health care. The cardiothoracic Surgery League (Liga de Cirurgia Cardiotorácica--LCCT), University of São Paulo Medical School, was founded 12 years ago, aimed at providing undergraduate medical students an opportunity to expand knowledge in cardiothoracic surgery and to take part in scientific studies in the field. OBJECTIVE To evaluate the experience gained through LCCT implementation. METHODS Current students and former members of LCCT were submitted to a specific evaluation form, delivered personally or by email, which provided data on the general opinion regarding LCCTs activities, the reasons for answers provided and choice of medical specialties. Furthermore, LCCTs total scientific production was evaluated. RESULTS Most undergraduate medical students 51/65 (78.5%) and former members 94/121 (77.7%) completed the form. The interest in Cardiothoracic Surgery was the most common reason for joining LCCT 44/161 (27.3%). Most students 32/51 (62.7%)--reported their initial expectations were partially met. Almost every member would recommend a fellow medical student to join LCCT 50/51 (98%) and 25/51 (49%) of them participated in a scientific project linked to LCCT. In total, 47 scientific papers were published having LCCTs medical students as authors or co-authors during the existence of the league. Of the former members who chose a surgical career, 7/52 (13.4%) chose thoracic or cardiovascular surgery. CONCLUSION LCCT has met its goals, since most current and former members recognized its role in their medical training, besides it is a good way to produce scientific initiation.

Cold ischemia or topical-ECMO for lung preservation: a randomized experimental study

CONTEXT AND OBJECTIVE Lung preservation remains a challenging issue for lung transplantation groups. Along with the development of ex vivo lung perfusion, a new preservation method known as topical-ECMO (extracorporal membrane oxygenation) has been proposed. The present study compared topical-ECMO with cold ischemia (CI) for lung preservation in an ex vivo experimental model. DESIGN AND SETTING Randomized experimental study, conducted at a public medical school. METHOD Fourteen human lungs were retrieved from seven brain-dead donors that were considered unsuitable for transplantation. The lung bloc was divided and each lung was randomized to be preserved by means of topical-ECMO or CI (4-7 °C) for eight hours. These lungs were then reconnected to an ex vivo perfusion system for functional evaluation. Lung biopsies were obtained at three times. The functional variables assessed were oxygenation capacity (OC) and pulmonary artery pressure (PAP); and the histological variables were lung injury score (LIS) and apoptotic cell count (ACC). RESULTS The mean OC was 468 mmHg (± 81.6) in the topical-ECMO group and 455.8 (± 54) for CI (P = 0.758). The median PAP was 140 mmHg (120-160) in the topical-ECMO group and 140 mmHg (140-150) for CI (P = 0.285). The mean LIS was 35.57 (± 4.5) in the topical-ECMO group and 33.86 (± 6.1) for CI (P = 0.367). The ACC was 25.00 (± 9.34) in the topical-ECMO group and 24.86 (± 10.374) for CI (P = 0.803). CONCLUSIONS The present study showed that topical-ECMO was not superior to cold ischemia for up to eight hours of lung preservation.