RESUMO
BACKGROUND: Compromised microvasculature resulting from disrupted bronchial arterial circulation appears to trigger chronic lung allograft dysfunction. Maintaining the microvasculature throughout the transplant process could improve the long-term health of transplanted lungs. We recently developed a bronchial-arterial-circulation-sparing (BACS) lung preservation approach and tested whether this approach would decrease microvascular damage and improve allograft function. METHODS: The lungs of Lewis rats were procured using either the BACS approach, where the bronchial and pulmonary arteries were synchronously perfused; a conventional approach, where only the pulmonary artery was perfused; or a conventional approach with a prostaglandin flush. After 4 hours of cold ischemia, physiologic function and vascular tone of the grafts were evaluated during ex vivo lung perfusion (EVLP), and microvasculature damage was assessed using 2-photon microscopy analysis. Lung function was compared after transplant among the groups. RESULTS: After 4 hours of cold ischemia, the BACS group exhibited significantly higher adenosine triphosphate levels and lower expression of phosphorylated myosin light chain, which is essential for vascular smooth muscle contraction. On EVLP, the BACS and prostaglandin groups showed lower pulmonary vascular resistance and less arterial stiffness. BACS attenuated microvasculature damage in the lung grafts when compared with conventional preservation. After transplantation, the lungs preserved with the BACS approach exhibited significantly better graft function and lower expression of phosphorylated myosin light chain. CONCLUSIONS: Our data suggest that BACS lung preservation protects the dual circulation inherent to the lungs, facilitating robust microvasculature in lung grafts after transplantation, leading to better posttransplant outcomes.
Assuntos
Rejeição de Enxerto/prevenção & controle , Transplante de Pulmão/efeitos adversos , Perfusão/métodos , Aloenxertos/irrigação sanguínea , Aloenxertos/patologia , Animais , Brônquios/irrigação sanguínea , Brônquios/patologia , Artérias Brônquicas/patologia , Artérias Brônquicas/transplante , Modelos Animais de Doenças , Circulação Extracorpórea/instrumentação , Circulação Extracorpórea/métodos , Rejeição de Enxerto/patologia , Humanos , Transplante de Pulmão/métodos , Masculino , Microvasos/patologia , Preservação de Órgãos , Soluções para Preservação de Órgãos , Perfusão/instrumentação , Pneumonectomia/métodos , Artéria Pulmonar/patologia , Artéria Pulmonar/transplante , Ratos , Ratos Endogâmicos Lew , Obtenção de Tecidos e Órgãos/métodos , Isquemia Quente/efeitos adversosRESUMO
Chronic allograft dysfunction (CLAD) remains a major complication, causing the poor survival after lung transplantation (Tx). Although strenuous efforts have been made at preventing CLAD, surgical approaches for lung Tx have not been updated over the last 2 decades. The bronchial artery (BA), which supplies oxygenated blood to the airways and constitutes a functional microvasculature, has occasionally been revascularized during transplants, but this technique did not gain popularity and is not standard in current lung Tx protocols, despite the fact that a small number of studies have shown beneficial effects of BA revascularization on limiting CLAD. Also, recent basic and clinical evidence has demonstrated the relationship between microvasculature damage and CLAD. Thus, the protection of the bronchial circulation and microvasculature in lung grafts may be a key factor to overcome CLAD. This review revisits the history of BA revascularization, discusses the role of the bronchial circulation in lung Tx, and advocates for novel bronchial-arterial-circulation sparing approaches as a future direction for overcoming CLAD. Although there are some already published review articles summarizing the surgical techniques and their possible contribution to outcomes in lung Tx, to the best of our knowledge, this review is the first to elaborate on bronchial circulation that will contribute to prevent CLAD from both scientific and clinical perspectives: from bedside to bench to bedside, and beyond.
Assuntos
Brônquios/irrigação sanguínea , Artérias Brônquicas/fisiologia , Pneumopatias/cirurgia , Transplante de Pulmão , Pulmão/irrigação sanguínea , Animais , Bronquiolite Obliterante/etiologia , Progressão da Doença , Rejeição de Enxerto/etiologia , Humanos , Microcirculação , Modelos Animais , Oximetria , Circulação Pulmonar , Transplante Homólogo/efeitos adversosRESUMO
Immune cell airway infiltration and the bronchovascular remodeling process have shown to be promising in the understanding of bronchiolitis obliterans (BO) pathogenesis. In this study we sought to validate the importance of immune cells, whether diffusely distributed or forming lymphoid follicles, collagen density, and vascular factors. Eight weeks after a single nitric acid (NA) nasal instillation, lung changes were characterized by lumen distortion, epithelial layer folding, reduction or total obliteration of terminal bronchiole (TB) lumen, and wall thickness increase. The morphologic changes in the TB and TA (terminal artery) lumen coincide with the measurement difference in the three groups. The TB diameter and lumen were significantly decreased in BO when compared with non-BO lungs (0.76 +/- 0.05 microm vs. 0.81 +/- 0.05 microm and 12,286.13 +/- 378.83 microm vs. 18,182.27 +/- 5,593.98 microm, p = 0.05 and p = 0.01, respectively). Equally significant was the increase in TB thickness in BO when compared with the non-BO group (201.72 +/- 35.75 microm vs. 149.75 +/- 40.61 microm, p = 0.007). The morphologic changes in immune cells seen in TB, TA, and bronchus-associated lymphoid tissue (BALT) also coincide with the quantification differences observed in the three groups. We concluded that immune cell infiltration and collagen/vascular remodeling are related to the spectrum of histologic changes in a BO nasal-induced model in mice and may be an appropriate target for prospective studies of human bronchiolitis.
Assuntos
Brônquios/efeitos dos fármacos , Brônquios/imunologia , Bronquiolite Obliterante/imunologia , Modelos Animais de Doenças , Ácido Nítrico/administração & dosagem , Administração Intranasal , Animais , Linfócitos B/imunologia , Brônquios/irrigação sanguínea , Brônquios/fisiologia , Bronquiolite Obliterante/patologia , Colágeno/fisiologia , Feminino , Imuno-Histoquímica , Instilação de Medicamentos , Macrófagos/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Neutrófilos/imunologia , Linfócitos T/imunologiaRESUMO
Dieulafoy's disease is a vascular anomaly characterized by the presence of a dysplastic artery that is related to an epithelial ulcer. While it is most frequently a GI condition, occurrence in the bronchus has been reported previously in six cases. We present the case of a 51-year-old man with severe hemoptysis and epistaxis. Chest radiographs showed diffuse density in the right base and a mass in the pedicle of T4. The results of bronchoscopy corroborated an active arterial bleeding point in the bronchus of the right middle lobe. A middle and lower lobectomy was performed with resection of the paravertebral mass. The final diagnoses were bronchial Dieulafoy's disease and paravertebral neurilemoma.
Assuntos
Malformações Arteriovenosas/diagnóstico , Brônquios/irrigação sanguínea , Hemoptise/etiologia , Neurilemoma/diagnóstico , Malformações Arteriovenosas/patologia , Malformações Arteriovenosas/cirurgia , Brônquios/patologia , Diagnóstico Diferencial , Humanos , Masculino , Pessoa de Meia-Idade , Neurilemoma/patologia , Neurilemoma/cirurgia , PneumonectomiaRESUMO
Misalignment of pulmonary vessels with alveolar capillary dysplasia is a rare cause of persistent pulmonary hypertension of the newborn. Most of the reported cases have been sporadic. We present two consecutive affected siblings with this disorder. This is the fifth reported family occurrence of this condition. In addition to the pulmonary abnormality, one of our cases had duodenal atresia.
Assuntos
Malformações Arteriovenosas/patologia , Pulmão/irrigação sanguínea , Síndrome da Persistência do Padrão de Circulação Fetal/patologia , Artéria Pulmonar/anormalidades , Veias Pulmonares/anormalidades , Brônquios/irrigação sanguínea , Capilares/anormalidades , Evolução Fatal , Feminino , Humanos , Recém-Nascido , Pulmão/patologia , Núcleo Familiar , Síndrome da Persistência do Padrão de Circulação Fetal/etiologia , Alvéolos Pulmonares/irrigação sanguíneaRESUMO
PURPOSE: This paper reviews the literature on the aetiology and therapy of bronchial hyperreactivity to describe the underlying pathophysiology, identify patients at risk and update knowledge on new and existing therapies. SOURCE: Information was obtained from monograms on New Drugs for Asthma, Respiratory Medicine: recent advances, Agents and Actions Supplements, Pulmonary Pharmacology, Anesth Analg, the European Journal of Respiration and a Medline literature search. PRINCIPAL FINDINGS: Reduced airway calibre, increased bronchial contractility, altered permeability of the bronchial mucosa, humoral and cellular mediators, and dysfunctional neural regulation are critical factors for bronchial hyperreactivity, a characteristic feature of hyperreactive airways which results in bronchoconstriction after exposure to varied stimuli. Preoperative anaesthetic considerations in these patients include FEV1 and PEFR testing to assess the severity and for optimal control of the condition. Bronchospasm causing hypoxaemia is the major intraoperative problem anticipated in these patients. Current therapeutic management of bronchoconstriction focuses on the beta 2 agonists, theophylline and steroids. Besides relaxing the airway smooth muscle these agents are all capable of altering bronchial inflammatory responses. Future developments of therapy are directed towards the inflammatory components of the disease. CONCLUSION: This review has presented background information on physiological mechanisms of smooth muscle contractility, pathophysiological alterations of bronchial contractility and the pharmacological basis of therapy in bronchoconstrictive disease. Information is presented to enable the prompt arrest and reversal of airway constriction, and to maintain prophylactic treatment during the perioperative period. Intraoperative bronchospasm is managed by adequate oxygenation and reversal of bronchoconstriction.
Assuntos
Hiper-Reatividade Brônquica/terapia , Brônquios/irrigação sanguínea , Hiper-Reatividade Brônquica/fisiopatologia , Cálcio/metabolismo , Canais de Cálcio/fisiologia , Glucocorticoides/uso terapêutico , Humanos , Canais de Potássio/fisiologia , Receptores Muscarínicos/fisiologia , Sistema Nervoso Simpático/fisiologiaRESUMO
The present study evaluated the effect of platelet activating factor (PAF) instilled into rat airways on vascular permeability assessed in isolated lung tissues by Evans blue (EB)-labelled plasma protein extravasation. It was found that intratracheal instillation of PAF induces a dose-dependent increase of EB extravasation in the bronchi (upper and inner) but not in the lung parenchyma. The contribution of eicosanoids to PAF-induced increase of vascular permeability was investigated by treating the animals with selected inhibitors prior to PAF administration. Mepacrine (5 mg/kg), L-663,536 (10 mg/kg), indomethacin (4 mg/kg) and dazoxiben (10 mg/kg) significantly reduced EB extravasation in the bronchi. The PAF antagonists BN-52021 (5 mg/kg), WEB-2086 (1 mg/kg), WEB-2170 (5 mg/kg) and PCA-4248 (3 mg/kg) were all effective in reducing the extravasation. These results suggest that PAF-induced increase of vascular permeability in rat bronchi is mediated by cyclooxygenase and lipoxygenase products of arachidonic acid metabolism.
Assuntos
Permeabilidade Capilar/efeitos dos fármacos , Pulmão/irrigação sanguínea , Fator de Ativação de Plaquetas/farmacologia , Animais , Proteínas Sanguíneas/metabolismo , Brônquios/irrigação sanguínea , Azul Evans , Extravasamento de Materiais Terapêuticos e Diagnósticos , Imidazóis/farmacologia , Indometacina/farmacologia , Masculino , Fator de Ativação de Plaquetas/administração & dosagem , Fator de Ativação de Plaquetas/antagonistas & inibidores , Quinacrina/farmacologia , Ratos , Ratos Wistar , TraqueiaRESUMO
Foram operados 26 caes, 14 com reimplantaçao pulmonar e 12 com "despleurizaçao hilar", para estudar alguns problemas decorrentes destas operaçoes, com destaque para a vascularizaçao arterial brônquica. Os resultados foram avaliados entre os 12 e os 24 meses, por intermédio de estudos in vivo (broncoscopias e exame bacteriológico das secreçoes brônquicas) e post-mortem (broncoarteriografias, moldes de injecçao-corrosao e exames anátomo-patológicos). Observaram-se 3 casos com complicaçoes pós-reimplante: 2 com bronquiectasias saculares sem aperto brônquico coexistente, e 1 com estenose da anastomose brônquica. Nos restantes animais nao se registraram alteraçoes. Em todos os casos observados, com ou sem complicaçoes, verificou-se o restabelecimento espontâneo de uma vascularizacao brônquica normal. Atribui-se à desnervaçao decorrente do reimplante um papel significativo na etiopatogenia das bronquiectasias; e em face da vascularizaçao brônquica normal e da ausência de infecçao no enxerto, considera-se que a estenose foi determinada por pequenos defeitos de técnica cirúrgica, dada a tendência que a mucosa tem em retrair-se depois da secçao do brônquio e que é considerada como um fator de desenvolvimento de fibrose. Valoriza-se o papel da circulaçao venosa pulmonar, com sangue arterializado, na revascularizaçao do coto do "brônquio dador".
Assuntos
Animais , Masculino , Feminino , Cães , Bronquiectasia/etiologia , Brônquios/cirurgia , Complicações Pós-Operatórias , Pulmão/cirurgia , Reimplante , Anastomose Cirúrgica/efeitos adversos , Brônquios/irrigação sanguíneaRESUMO
Lung transplantation has been slow to develop due mainly to the association of complications at the bronchial anastomosis secondary to the devascularization incurred during procurement. In the present study we evaluate the importance of the protection of the bronchial anastomoses with an omental pedicle. Mongrel dogs were operated upon forming four study groups: lung allotransplantation with bronchial protection (group T1, n = 9), lung allotransplantation without protection (group T2, n = 6); the two remaining groups did not receive a transplant but instead underwent surgery with extensive dissection and transection with reanastomoses of the left main bronchus with (group B1, n = 5) and without (group B2, n = 5) bronchial protection. All animals survived the surgical procedure. There were 8 complications at the bronchial anastomosis, six of which appeared in group T2 and were directly responsible for the animals death (p less than 0.05 when comparing lethal complications with group T1). Angiographic and dye perfusion studies were performed through the right gastroepiploic artery of the omentum. Bronchial neovascularization was demonstrated macroscopically as well as with light microscopy in all animals receiving protection with omentum (groups T1 and B1). We conclude that adequate bronchial protection is achieved with an omental pedicle flap brought up to the thorax during lung transplantation. It diminishes significantly the incidence of lethal complications at the bronchial anastomosis due to the revascularization that occurs through the omentum.