Marcelo A.C. Vaz

Pleurodesis Induced by Talc or Silver Nitrate: Evaluation of Collagen and Elastic Fibers in Pleural Remodeling

This study evaluated the extracellular matrix (collagen and elastic fibers) in pleurodesis induced by intrapleural talc (TL) or silver nitrate (SN). Study subjects were 420 rabbits divided into two groups and sacrificed from 15 min to 12 months after the injection of the sclerosing agents at intervals previously defined. Pleural adhesions and fibrosis were graded (0–4), and the collagen and elastin were quantified. The maximum score of the pleural adhesions was observed two months after TL (2.80 ± 0.99) and 15 days after SN (3.75 ± 0.25). More intense pleural adhesions were observed in the SN group from day 5 (p < 0.05). Pleural thickness and pleural fibrosis were, in general, significantly higher after SN (p < 0.05). Increased deposition of collagen and elastin was observed in both groups but was more evident in the SN group. In the TL group, a linear correlation was observed between pleural adhesions and fibrosis (r = 0.775), between pleural adhesions and collagen (r = 0.779), and between fibrosis and collagen (r = 0.709). In the SN group, these correlations were acceptable (r = 0.605, 0.665, and 0.663). The elastin presented a correlation of 0.707 (p < 0.001) in the TL group and of 0.564 (p < 0.001) in the SN group. In conclusion, intrapleural 0.5% silver nitrate and talc (400 mg/kg) are effective in the induction of pleurodesis. However, the intensity of adhesions and the richness of collagen after SN, in combination with the early onset of tissue remodeling, demonstrate the local superiority of this agent. Considering the easy availability and instillation, the low cost, and the absence of important side effects, silver nitrate might be considered as a sclerosing agent to induce pleurodesis in humans.

Reexpansion pulmonary edema

O edema pulmonar de reexpansao e uma entidade rara, mas de notavel mortalidade. Sua fisiopatologia ainda nao e bem esclarecida, porem envolve fatores conhecidos, como a diminuicao do surfactante pulmonar, e outros ainda incertos, como o papel dos mediadores inflamatorios na genese e manutencao do processo. E imperativo o diagnostico precoce, uma vez que o desfecho depende da agilidade no reconhecimento e tratamento dessa entidade. Tendo em vista a alta mortalidade, as medidas de prevencao ainda sao a melhor estrategia no manuseio dos pacientes com doencas que podem levar ao edema pulmonar de reexpansao. Esta revisao discute os principais aspectos relacionados a fisiopatologia, diagnostico, tratamento e prevencao do edema pulmonar de reexpansao, com recomendacoes praticas para o reconhecimento e adequada abordagem dessa entidade.

Does the evaluation of coagulation factors contribute to etiological diagnosis of pleural effusions

OBJECTIVE The aim of this study was to identify the participation of the coagulation system in the differential diagnosis of pleural effusions. INTRODUCTION Imbalance between immunologic and metabolic factors triggers a sequence of events resulting in pleural reactions and accumulation of fluid. The coagulation system, which is fundamental for the maintenance of homeostasis, contributes to the inflammatory process responsible for pleural effusions, and participates in cellular proliferation and migration as well as in the synthesis of inflammatory mediators. METHODS We evaluated the laboratory profile of coagulation and fibrinolysis in 54 pleural fluids (15 transudates and 39 exudates). RESULTS The coagulation system acts according to the pathophysiologic mechanisms involved in the development of pleural effusions. In inflammatory effusions (exudates), there is activation of coagulation with increased levels of fragment 1+2 and thrombin-antithrombin complex in addition to reduction of fibrinogen levels due to fibrinolysis and fibrin tissue incorporation. As a consequence, there is activation of the fibrinolytic system with increased levels of fibrin degradation products, including the D-dimer. These changes are not sufficient for differentiation of different subgroups of exudates. In transudates, these events were observed to a lesser degree. CONCLUSION The coagulation system plays an important role in the development of pleural diseases. Coagulation tests show differences between transudates and exudates but not among exudate subgroups. Understanding the physiopathological mechanisms of pleural disorders may help to define new diagnostic and therapeutic approaches.

Low Concentration Silver Nitrate Pleurodesis in Rabbits: Optimal Concentration for Rapid and Complete Sclerosing Effect

Pleurodesis is a useful therapeutic tool when local treatment of a recurrent malignant pleural effusion or pneumothorax is needed. We have previously demonstrated that the intrapleural injection of 0.5% silver nitrate (SN) produces a significant pleurodesis, while 0.25% SN has no sclerosing effect in a rabbit model. The objective of this study was to determine the minimum concentration of SN needed to induce pleurodesis in our experimental model. One hundred twenty male New Zealand white rabbits received 0.3, 0.4, or 0.5% SN (40 animals per group) in a total volume of 2 mL instilled intrapleurally. These animals were sacrificed 3, 7, 14 or 28 days after the intrapleural injection (n = 10 animals per group), and the pleural spaces were then assessed grossly for evidence of pleurodesis and microscopically for evidence of fibrosis and inflammation. By 28 days, all concentrations of SN had produced a pleurodesis. There was evidence of a gross pleurodesis 7 days post-injection in animals that received 0.5% SN (score of 2.8 ± 0.2 on a scale of 0–4). After 14 days, significant pleural adhesions were evident in the groups that received 0.4 or 0.5% SN. We conclude that SN concentrations as low as 0.3% can effectively produce a pleurodesis within 28 days of intrapleural injection. However, the precocious pleurodesis development observed 7 days after the intrapleural injection of 0.5% SN suggests that this concentration may be optimal when a fast result is necessary.

Cholesterol in the separation of transudates and exudates.

The Light criteria represent the most acceptable method to separate transudates and exudates. However, approximately 10% of patients with transudates, especially those with congestive heart disease, are misdiagnosed with these criteria. To improve diagnostic accuracy, many biochemical markers have been proposed as alternatives to differentiate transudates and exudates. Cholesterol has raised particular interest because only pleural fluid is needed, which makes blood samples unnecessary and simplifies the procedure. In most clinical studies, cholesterol has been shown to be as sensitive as the Light criteria, although it is less specific. Other randomized studies are necessary to determine the real potential value of pleural-fluid cholesterol measurements. Studies of pleural-fluid cholesterol are aimed at better understanding the mechanisms by which cholesterol enters the pleural cavity and its role in diseases. The ideal cutoff point of cholesterol to differentiate transudates and exudates is still unknown. Recently, aspects of the cholesterol turnover in diseases have raised great interest. Cholesterol generated great interest after it was related to coronary artery diseases. The involvement of cholesterol in the atherosclerotic process is well known, although its importance in body cavities is still unclear.

Effectiveness of silver nitrate compared to talc slurry as pleural sclerosing agent in rabbits. Influence of concomitant intrapleural lidocaine

UNLABELLED The ideal agent for producing pleurodesis has not been identified. Talc, the most commonly used, poses several problems. Another possibility is silver nitrate, which was widely used in the past. PURPOSE To determine the influence of the intrapleural instillation of lidocaine in producing a pleurodesis with silver nitrate, to define the effect of lidocaine in the maturation of the collagen fibers, and to confirm that the pleurodesis after silver nitrate is stronger than after talc. METHODS We studied three groups of 8 rabbits. Two groups received 0.5% silver nitrate; in one we had previously injected 0.5 ml of 2% lidocaine. The third group received 400 mg/kg talc (2 ml). The animals were sacrificed 28 days after the injection, and the pleural spaces were assessed grossly for evidence of pleurodesis and microscopically for evidence of inflammation and fibrosis. The total amount of pleural collagen and the distribution of thick and thin collagen fibers were quantified. Collagen was identified using picrosirius red stain. RESULTS In the two groups that received silver nitrate (without lidocaine: 3.5 + 03 and with lidocaine: 3.2 + 0.3), the macroscopic pleurodesis (scale 0 - 4) was significantly (p = 0.001) better than that resulting from talc (1.6 + 0.2). The mean degree of pleural fibrosis induced by silver nitrate (3.5 + 0.2) was significantly (p = 0.004) higher than that induced by talc (1.9 + 0.1). The previous instillation of lidocaine resulted in a tendency for decreased amounts of fibrosis (3.1 + 0.4). The mean amount (10(3)mm2) of pleural collagen was significantly (p = 0.009) greater in the rabbits that received silver nitrate (116.9 + 22.7) than in those that received talc (10.7 + 3.4). The injection of lidocaine slightly reduced the collagen (80.1 + 30.3). The distribution of collagen fibers did not differ among the groups. CONCLUSION This rabbit model clearly confirms that intrapleural silver nitrate is more effective than talc for producing pleurodesis. The previous intrapleural instillation of lidocaine results in a decreasing trend in the amount of collagen, but does not change the effectiveness of the pleural fusion or modify the process of collagen maturation.

Linfoma primário de cavidade pleural em paciente imunocompetente

Primary effusion lymphoma is an unusual non-Hodgkins lymphoma rarely seen in immunocompetent patients. Herein, we present clinical and biochemical data obtained from an immunocompetent patient diagnosed with primary effusion lymphoma.

The proliferative cytokines TGF-β and VEGF in pleural effusions post-coronary artery bypass graft

UNLABELLED Coronary artery bypass graft (CABG) surgeries can impact on the pericardium and pleural space, leading to inflammation which can cause effusion. AIM To study the role of the proliferative cytokines TGF-beta and VEGF in the fluids of 16 transudates and 43 pleural effusions of patients who underwent CABG at the Heart Unit and Pulmonology Unit of the University Hospital of São Paulo. Levels of cytokines were assessed 2, 24 and 48 hours post-surgery. RESULTS The pleural effusion after CABG is an exsudative mobilizer of TGF-beta and VEGF cytokines immediately after surgery. The TGF-beta concentrations were elevated 2 hours after surgery but started to fall soon after, reaching transudate levels after 48 hours. VEGF levels were high in the first 2 hours post surgery and tended to maintain the same concentrations for at least 48 hours after surgery. CONCLUSIONS Based on the results obtained, TGF-beta is a cytokine that seems to work as a trigger, leading the pleural mesothelial cell to express VEGF a cause of pleural effusion in CABG surgeries.

Papel das citocinas proliferativas TGF-β e VEGF no derrame pleural pós-revascularização do miocárdio

Resumo A cirurgia de revascularizacao do miocardio envolve o acometimento, tanto do pericardio como da pleura, conduzindo ao favorecimento de processos inflamatorios responsaveis pelo desenvolvimento de derrames nestes compartimentos. Objectivo: Estudar o comportamento das citocinas proliferativas TGF-β (factor beta de transformacao do crescimento) e VEGF (factor de crescimento do endotelio vascular) nos liquidos de 16 transudatos e de 43 derrames pleurais de doentes submetidos a cirurgias de revascularizacao do miocardio provenientes do Instituto de Coracao e do Servico de Pneumologia da Universidade do Sao Paulo nos intervalos de 2, 24 e 48 horas de pos-operatorio. Resultados: O derrame pleural pos-revascularizacao do miocardio e um exsudato mobilizador de TGF-β e VEGF no pos-operatorio imediato. Os niveis de TGF-β apresentam-se elevados nas primeiras 2 horas para cairem progressivamente ate se aproximarem dos valores dos transudatos ao fim de 48 horas, enquanto o VEGF se inicia com niveis elevados ja nas primeiras 2 horas com tendencia a aumento pelo menos ate 48 horas de pos-operatorio. Conclusoes: O TGF-β parece comportar-se como elemento gatilho sobre a celula mesotelial pleural para a liberacao de VEGF no desenvolvimento de derrame pleural nas cirurgias de revascularizacao do miocardio. Rev Port Pneumol 2006; XII (4): 359-367

Pleurodesis induced by intrapleural injection of silver nitrate or talc in rabbits: can it be used in humans?

OBJETIVO DE ESTUDO: Avaliar as alteracoes pleuropulmonares causadas pela injecao intrapleural de talco ou nitrato de prata em modelo experimental, com o intuito de considerar sua utilizacao em humanos. METODO: 112 coelhos foram aleatoriamente escolhidos para receber, no espaco pleural, 400mg/kg de talco em 2ml de solucao salina ou 2ml de nitrato de prata a 0,5%, sendo oito animais, em cada grupo, sacrificados apos um, dois, quatro, seis, oito, 10 ou 12 meses. Em relacao a cavidade pleural, foram analisados o grau de pleurodese macroscopica (aderencias) e as alteracoes microscopicas representadas por inflamacao e fibrose dos folhetos pleurais. O parenquima foi avaliado quanto ao grau de colapso alveolar, edema dos septos interalveolares e celularidade em escore de 0 a 4. RESULTADOS: A injecao intrapleural de nitrato de prata produziu pleurodese mais precoce e mais intensa do que a injecao de talco. A lesao parenquimatosa foi mais evidente com nitrato de prata, sendo considerada de grau moderado e restrita a primeira avaliacao (um mes). A partir do segundo mes, e durante todo o seguimento de um ano, a lesao parenquimatosa foi semelhante com ambas as substâncias, sendo apenas as aderencias pleurais mais intensas com nitrato. CONCLUSOES: O nitrato de prata intrapleural produz melhor e mais duradoura pleurodese do que a injecao intrapleural de talco. As alteracoes parenquimatosas, apesar de discretas, sao mais pronunciadas com o uso de nitrato de prata, sendo, porem, minimas apos dois meses e semelhantes, durante todo o periodo de observacao de um ano, as encontradas com o uso do talco. Esses efeitos sobre o parenquima pulmonar nao contra-indicam seu uso em seres humanos. Dessa forma, o uso do nitrato de prata intrapleural, com o intuito de produzir rapida e efetiva pleurodese, pode ser considerado nos pacientes em que se deseja a sinfise da cavidade pleural.