Aristides Tadeu Correia

Risk Factors and Survival Impact of Primary Graft Dysfunction After Lung Transplantation in a Single Institution

BACKGROUND Lung transplantation has become a standard procedure for some end-stage lung diseases, but primary graft dysfunction (PGD) is an inherent problem that impacts early and late outcomes. The aim of this study was to define the incidence, risk factors, and impact of mechanical ventilation time on mortality rates among a retrospective cohort of lung transplantations performed in a single institution. METHODS We performed a retrospective study of 118 lung transplantations performed between January 2003 and July 2010. The most severe form of PGD (grade III) as defined at 48 and 72 hours was examined for risk factors by multivariable logistic regression models using donor, recipient, and transplant variables. RESULTS The overall incidence of PGD at 48 hours was 19.8%, and 15.4% at 72 hours. According multivariate analysis, risk factors associated with PGD were donor smoking history for 48 hours (adjusted odds ratio [OR], 4.83; 95% confidence interval [CI], 1.236-18.896; P = .022) and older donors for 72 hours (adjusted OR, 1.046; 95% CI, 0.997-1.098; P = .022). The operative mortality was 52.9% among patients with PGD versus 20.3% at 48 hours (P = .012). At 72 hours, the mortality rate was 58.3% versus 21.2% (P = .013). The 90-days mortality was also higher among patients with PGD. The mechanical ventilation time was longer in patients with PGD III at 48 hours namely, a mean time of 72 versus 24 hours (P = .001). When PGD was defined at 72 hours, the mean ventilation time was even longer, namely 151 versus 24 hours (P < .001). The mean overall survival for patients who developed PGD at 48 hours was 490.9 versus 1665.5 days for subjects without PGD (P = .001). Considering PGD only at 72 hours, the mean survival was 177.7 days for the PGD group and 1628.9 days for the other patients (P < .001). CONCLUSION PGD showed an important impacts on operative and 90-day mortality rates, mechanical ventilation time, and overall survival among lung transplant patients. PGD at 72 hours was a better predictor of lung transplant outcomes than at 48 hours. The use of donors with a smoking history or of advanced age were risk factors for the development of PGD.

Atrial Coronary Arteries in Areas Involved in Atrial Fibrillation Catheter Ablation

Background—The proximity to vascular structures is a limiting factor during radiofrequency ablation. However, little or no attention has been given to the atrial arterial circulation during the development of atrial fibrillation (AF) catheter ablation techniques. Methods and Results—We examined the atrial arterial circulation in areas involved in AF ablation in 24 heart specimens by colored resin injection and careful dissection. The sinus node artery (SNA) arose from the circumflex artery in 42% of case; proximal to the LA appendage in 29%, crossing the left atrium (LA) anterior wall; and after the LA appendage in the remaining 13%, crossing the mitral isthmus and passing close to the left pulmonary veins (PVs), the LA roof, and the right superior PV. In 58%, the SNA arose from the right coronary artery. Major arteries (≥1 mm in external diameter) were found in the mitral isthmus in 54%, at the LA roof in 54%, and at the LA anterior wall in 29%. Around the left PV ostia, there were areas with major arteries in up to 37% (at the roof and inferior segments) and around the right PV ostia in up to 29% (at the roof segment). Conclusions—Major atrial coronary arteries, including the SNA, were commonly found in the areas involved in AF ablation and could cause difficulties in obtaining transmural lesions and electric isolation or even lead to ischemic sinus node or atrial dysfunction.

Comparison Between Perfadex and Locally Manufactured Low-Potassium Dextran Solution for Pulmonary Preservation in an Ex Vivo Isolated Lung Perfusion Model

INTRODUCTION Lung transplantation, a consolidated treatment for end-stage lung disease, utilizes preservation solutions, such as low potassium dextran (LPD), to mitigate ischemia-reperfusion injury. We sought the local development of LPD solutions in an attempt to facilitate access and enhance usage. We also sought to evaluate the effectiveness of a locally manufactured LPD solution in a rat model of ex vivo lung perfusion. METHODS We randomized the following groups \?\adult of male Wistar rats (n = 25 each): Perfadex (LPD; Vitrolife, Sweden); locally manufactured LPD-glucose (LPDnac) (Farmoterapica, Brazil), and normal saline solution (SAL) with 3 ischemic times (6, 12, and 24 hours). The harvested heart-lung blocks were flushed with solution at 4°C. After storage, the blocks were connected to an IL-2 Isolated Perfused Rat or Guinea Pig Lung System (Harvard Apparatus) and reperfused with homologous blood for 60 minutes. Respiratory mechanics, pulmonary artery pressure, perfusate blood gas analysis, and lung weight were measured at 10-minute intervals. Comparisons between groups and among ischemic times were performed using analysis of variance with a 5% level of significance. RESULTS Lungs preserved for 24 hours were nonviable and therefore excluded from the analysis. Those preserved for 6 hours showed better ventilatory mechanics when compared with 12 hours. The oxygenation capacity was not different between lungs flushed with LPD or LPDnac, regardless of the ischemic time. SAL lungs showed higher PCO(2) values than the other solutions. Lung weight increased over time during perfusion; however, there were no significant differences among the tested solutions (LPD, P = .23; LPDnac, P = .41; SAL, P = .26). We concluded that the LPDnac solution results in gas exchange were comparable to the original LPD (Perfadex); however ventilatory mechanics and edema formation were better with LPD, particularly among lungs undergoing 6 hours of cold ischemia.

Effects of mycophenolate sodium on mucociliary clearance using a bronchial section and anastomosis rodent model

OBJECTIVE: To study the effects of mycophenolate sodium on mucociliary clearance. INTRODUCTION: Mycophenolate is one of the most commonly used immunosuppressive drugs in lung transplantation. Although its pharmacokinetic properties are well defined, its side effects on mucociliary clearance have not yet been studied. METHODS: Sixty rats were subjected to left bronchial section and anastomosis. The right bronchus was used as a control. After surgery, the rats were assigned to two groups based on whether they received saline solution (n = 30) or mycophenolate sodium (n = 30). After 7, 15, or 30 days of treatment, 10 animals from each group were sacrificed, and in vitro mucus transportability, in situ mucociliary transport velocity and ciliary beat frequency were measured. RESULTS: The analysis of mucus transportability revealed that neither mycophenolate nor bronchial section altered any transportability related property for up to 30 days of treatment after surgery (p>0.05). With regard to ciliary beat frequency, the operated left bronchi from the mycophenolate group showed a significant decrease on post-surgical day 30 (p = 0.003). In addition, we found a significant reduction in the in situ mucociliary transport velocity in the mycophenolate-treated group (p = 0.0001). DISCUSSION: These data add important information regarding mucociliary clearance dysfunction following mycophenolate therapy and suggest that mycophenolate might contribute to the high incidence of respiratory tract infections in lung transplant patients. Further studies are needed to investigate the combined action of mycophenolate with other immunosuppressive drugs and to establish methods to protect and recover mucociliary clearance, an important airway defense mechanism.

Modelo experimental de perfusão pulmonar ex vivo em ratos: avaliação de desempenho de pulmões submetidos à administração de prostaciclina inalada versus parenteral

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 4oC 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.

Hematological parameters and nuclear abnormalities in peripheral erythrocytes of Achirus lineatus (Pleuronectiformes: Achiridae)

Hematological parameter of demersal fish constitutes important measures of biological effects of seasonality and contaminants in sediments. We aimed to assess the hematological parameters and nuclear abnormalities, including micronuclei levels, in peripheral erythrocytes of flatfish Achirus lineatus collected in São Vicente Estuary in summer and winter. The number of lymphocytes was significantly higher in summer, whereas the number of neutrophils was significantly higher in winter. For other measured parameters, no significant differences were observed in spite of the levels of erythroblasts, leukocytes, thrombocytes, micronuclei and nuclear abnormality tended to be slightly higher in winter. Integrated analysis of data suggests that genotoxicity may be related to immunosuppression, although some types of leukocytes appear to act removing anomalous cells. Considering the contamination status of the Santos–São Vicente Estuarine system, the results provide an important contribution to knowledge of the hematological aspects of A.lineatus and its potential use as a bioindicator for monitoring estuarine sites.

Influence of cyclosporine A on mucociliary system after lung transplantation in rats

OBJETIVO: Investigar a funcao do sistema mucociliar em ratos transplantados sob a influencia de imunossupressores. METODOS: Trinta e seis ratos foram submetidos ao transplante pulmonar unilateral e divididos em dois grupos, onde um grupo foi tratado com ciclosporina e outro foi controle. Administrada ciclosporina por via subcutânea na dose de 10 mg/kg diariamente. Os ratos foram sacrificados 2, 15 e 30 dias apos o transplante pulmonar. O transporte mucociliar bronquico (TMC) in situ e a frequencia de batimento ciliar (FBC) foram analisados na porcao proximal e distal a anastomose bronquica. Realizada correlacao dos achados com parâmetros gasometricos e histologia. RESULTADOS: Foi encontrada melhora progressiva e significante no TMC na regiao proximal e distal a anastomose no grupo que recebeu ciclosporina em 15 e 30 dias (p<0,01). Nao houve diferenca na FBC nos dois grupos estudados. A analise histologica mostrou que a rejeicao foi significantemente maior no grupo controle (p<0,05). A oxigenacao foi melhor nos animais que receberam a ciclosporina. CONCLUSAO: A ciclosporina exerceu influencia positiva no transporte mucociliar bronquico, provavelmente por sua acao imunossupressora.

Comparing the Performance of Rat Lungs Preserved for 6 or 12 Hours After Perfusion With Low-Potassium Dextran or Histidine–Tryptophan–Ketoglutarate

INTRODUCTION In lung transplantation, graft dysfunction is a frequent cause of mortality; the etiopathogenesis is related to ischemia-reperfusion injury. We sought to compare the lung performance of rats after reperfusion after presentation with 3 solutions at 2 ischemia times. METHODS We randomized 60 male Wistar rats to undergo anterograde perfusion via the pulmonary artery with low-potassium dextran (LPD), histidine-tryptophan ketoglutarate (HTK), or saline. After extraction, the heart-lung blocks were preserved in a solution at hypothermia for 6 or 12 hours before perfusion with homologous blood for 60 minutes using ex vivo system Isolated Perfused Rat or Guinea Pig Lung System (Harvard Apparatus). Respiratory mechanics, pulmonary weight, pulmonary artery pressure (PAP), and relative lung oxygenation capacity (ROC) measurements were obtained every 10 minutes. RESULTS Comparing tidal volume (TV), compliance, resistance, ROC, PAP, and pulmonary weight the LPD, HTK, and saline group did not differ at 6 and 12 hours. The TV was higher in the lungs with 6-hour ischemia in the LPD, HTK, and saline groups. Compliance was higher in the lungs with 6-hour ischemia in the LPD and saline groups. There were no differences in ROC values comparing lungs with 6- versus 12-hour ischemia in the LPD group. A significant difference was observed between lungs in the HTK and saline groups. Resistance was higher in the lungs with 12-hour ischemia among the LPD, HTK, and saline groups. There was a gradual weight increase in the lungs, particularly those undergoing 12-hour ischemia, despite the absence of a significant difference between groups. CONCLUSION Rat lungs perfused with LPD and HTK preservation solutions showed similar reperfusion performances in this ex-vivo perfusion model.

The effects on mucociliary clearance of prednisone associated with bronchial section

OBJECTIVE: Infections have been and remain the major cause of morbidity and mortality after lung transplantation. Because mucociliary clearance plays an important role in human defense mechanisms, the influence of drugs on the mucociliary epithelium of patients undergoing lung transplantation must be examined. Prednisone is the most important corticosteroid used after lung transplantation. The aim of this study was to evaluate the effects of bronchial transection and prednisone therapy on mucociliary clearance. METHODS: A total of 120 rats were assigned to 4 groups according to surgical procedure or drug therapy: prednisone therapy (1.25 mg/kg/day); bronchial section and anastomosis + prednisone therapy (1.25 mg/kg/day); bronchial section + saline solution (2 ml/day); and saline solution (2 ml/day). After 7, 15, or 30 days, the animals were sacrificed, and the lungs were removed from the thoracic cavity. The in situ mucociliary transport velocity, ciliary beat frequency and in vitro mucus transportability were evaluated. RESULTS: Animals undergoing bronchial section surgery and anastomosis had a significant decrease in the ciliary beat frequency and mucociliary transport velocity 7 and 15 days after surgery (p<0.001). These parameters were normalized 30 days after the surgical procedure. Prednisone improved mucous transportability in the animals undergoing bronchial section and anastomosis at 15 and 30 days (p<0.05). CONCLUSION: Bronchial section and anastomosis decrease mucociliary clearance in the early postoperative period. Prednisone therapy improves mucus transportability in animals undergoing bronchial section and anastomosis.

Alternative solution for ex vivo lung perfusion, experimental study on donated human lungs non-accepted for transplantation

PURPOSE To evaluate a new perfusate solution to be used for ex vivo lung perfusion. METHODS Randomized experimental study using lungs from rejected brain-dead donors harvested and submitted to 1 hour of ex vivo lung perfusion (EVLP) using mainstream solution or the alternative. RESULTS From 16 lungs blocs tested, we found no difference on weight after EVLP: Steen group (SG) = 1,097±526g; Alternative Perfusion Solution (APS) = 743±248g, p=0.163. Edema formation, assessed by Wet/dry weigh ratio, was statistically higher on the Alternative Perfusion Solution group (APS = 3.63 ± 1.26; SG = 2.06 ± 0.28; p = 0.009). No difference on PaO2 after EVLP (SG = 498±37.53mmHg; APS = 521±55.43mmHg, p=0.348, nor on histological analyses: pulmonary injury score: SG = 4.38±1.51; APS = 4.50±1.77, p=0.881; apoptotic cells count after perfusion: SG = 2.4 ± 2.0 cells/mm2; APS = 4.8 ± 6.9 cells/mm2; p = 0.361). CONCLUSION The ex vivo lung perfusion using the alternative perfusion solution showed no functional or histological differences, except for a higher edema formation, from the EVLP using Steen Solution(r) on lungs from rejected brain-dead donors.