Cell Death in Human Lung Transplantation: Apoptosis Induction in Human Lungs During Ischemia and After Transplantation

Fischer, Stefan; Cassivi, Stephen D.; Xavier, Alexandre M.; Cardella, Jonathan; Cutz, Ernest; Edwards, Vern; Liu, Mingyao; Keshavjee, Shaf

doi:10.1097/00000658-200003000-00016

Cited by 169 publications

(147 citation statements)

References 41 publications

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“…20 Fischer et al found that there was a significant increase in the number of apoptotic cells two hours after graft reperfusion. 21 These studies demonstrated that there was a significant correlation between the percentage of necrotic cells and deterioration of graft function, as estimated by means of PaO 2 after implantation.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2014

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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. RESUMO CONTEXTO E OBJETIVO:A preservação pulmonar permanece um desafio para os grupos transplantadores. Com o desenvolvimento da perfusão pulmonar ex vivo, foi proposto um novo método de preservação chamado de ECMO-tópico (oxigenação de membrana extracorpórea). O presente estudo compara ECMOtópico com isquemia fria (IF) para preservação pulmonar em um modelo experimental ex vivo. TIPO DE ESTUDO E LOCAL: Estudo experimental randomizado, conduzido em uma faculdade de medicina pública. MÉTODO: Quatorze pulmões humanos foram retirados de sete doadores de morte cerebral considerados não aptos a transplante. O bloco pulmonar foi dividido e cada um foi aleatorizado para preservação por ECMO-tópico ou IF (4-7 °C) durante oito horas. Esses pulmões foram então re-conectados a um sistema de perfusão ex vivo para avaliação funcional. Biópsias pulmonares foram obtidas em três tempos. As variáveis funcionais avaliadas foram: capacidade de oxigenação (CO) e pressão de artéria pulmonar (PAP). As variáveis histológicas estudadas foram escore de lesão pulmonar (ELP) e contagem de células apoptóticas (CCA). RESULTADOS: A média da CO foi de 468 mmHg (± 81.6) no grupo ECMO-tópico e 455.8 (± 54) no grupo IF (P = 0,758); a PAP média foi de 140 mmHg (120-160) para ECMO-tópico e 140 mmHg (140-150) para IF (P = 0,285); o ELP médio foi 35,57 (± 4,5) no ECMO-tópico e 33,86 (± 6,1) no IF (P = 0,367). A CCA foi 25,00 (± 9,34) no grupo ECMO-tópico e 24,86 (± 10,374) no IF (P = 0...

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Section: Discussionmentioning

confidence: 99%

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

et al. 2014

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“…Although apoptosis plays an important role in the immune system and during tissue repair, there are several potential mechanisms by which apoptosis might play a role in ARDS. Apoptosis was described during ARDS particularly in the population of neutrophils [5], endothelial cells [6], myofibroblasts [7], and pericytes [8], as well as in alveolar epithelial cells [9].…”

Section: Discussionmentioning

confidence: 99%

“…No significant correlation between apoptosis and clinical physiological function of the lungs has been confirmed. Fisher et al [9] found that up to 34% of pulmonary cells underwent apoptotic cell death after transplantation of lungs without significant alteration of their function in humans. The authors hypothesized that a high index of apoptosis in transplanted organs indicates their ability to eliminate injured cells and avoid the more destructive process of necrosis.…”

Section: Discussionmentioning

confidence: 99%

Adult Respiratory Distress Syndrome and alveolar epithelium apoptosis: an histopathological and immunohistochemical study.

Tóth

Pingorová²,

Jonecová³

et al. 2010

Folia Histochem Cytobiol.

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Adult Respiratory Distress Syndrome results from a variety of different initial insults, including trauma, sepsis, pneumonia and aspiration, and represents a severe form of acute lung injury. The lung samples of a 20-year-old man who had suffered a serious motorbike accident were obtained for histological examination. He died on the seventh day as a consequence of respiratory failure. The typical histopathological features of syndrome overlapping the first exudative phase into the second proliferate phase were observed. The apoptotic index of the early apoptotic phase evaluated using M30CytoDEATH was 3.4±0.2. The average number of apoptotic cells in the intermediate and late phases measured using the TUNEL method was 9.8±0.7. Our findings indicate that alveolar epithelium apoptosis seems to be less important during the early phases of Adult Respiratory Distress Syndrome.

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“…Structural and functional damage in I/R injury results in leukocyte accumulation and adherence to venules, platelet aggregation, vasoconstriction and deterioration of capillary perfusion, which can be quantified by intravital fluorescence microscopy [38]. Recent studies have determined the contribution of apoptosis to total cell death after I/R injury in several organs, such as kidney [17], heart [18], liver [19], lung [20] and small bowel [21]. Apoptosis is involved in a variety of physiological and pathophysiological processes.…”

Section: Discussionmentioning

confidence: 99%

“…However, recent studies have emphasized the contribution of apoptosis to organ cell death after ischemia-reperfusion injury in several organs, such as the kidney [17], heart [18], liver 1191, lung [20] and small bowel [21]. Thus, increased apoptotic cell death might be an unspecific marker for I/R injury.…”

Section: Introductionmentioning

confidence: 99%

Ischemic preconditioning fails to improve microcirculation but increases apoptotic cell death in experimental pancreas transplantation

et al. 2004

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Brief periods of warm ischemia and subsequent short reperfusion before either long-term cold or warm ischemic insult (ischemic preconditioning, IPC) have proven to ameliorate ischemia/reperfusion (I/R) injury in various organs, such as the liver and lung. The aim of this study was to examine the effect of IPC on pancreatic cell apoptosis and microcirculatory impairments in experimental pancreas transplantation. Male Lewis rats served as donors and recipients of heterotopic syngeneic pancreaticoduodenal transplantation. Recipient animals were divided into two experimental groups: group Tx (n = 7) received grafts without IPC, group Tx&IPC received grafts with TPC. Animals that had not undergone transplantation but whcse pancreata had been exteriorized served as controls (n = 5). All pancreatic grafts were preserved in University of Wisconsin solution for 6 h at 4°C. IPC was induced by interruption of the arterial blood flow for 10 inin followed by 10 min of reperfusion. One and two hours after reperfusion, graft microcirculation was assessed by means of intravital microscopy (IVM). Rats were immediately killed after the second measurement and DNA breaks of acinar cells were detected by in situ terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate digoxigenin nick end-labelling (TUNEL) assay and gel electrophoresis (laddering). The apoptotic index (AI) was defined as the number of apoptotic cells per high-power field. Analysis of both groups of transplanted grafts showed a significant decrease in functional capillary density (FCD) and a significant increase in leukocyte sticking to postcapillary venules (LAV) at 1 h and 2 h of reperfusion, compared with animals that had not undergone transplantation (P < 0.01). In parallel, A1 was significantly increased in transplanted grafts compared to the controls (P < 0.01). Grafts subjected to IPC showed no significant differences, neither for FCD nor LAV, at both time points if compared with grafts of group Tx. However, IPC resulted in a significant increase in A1 (P < 0.05). We can conclude that IPC has no effect on pancreatic microcirculation but enhances acinar cell apoptosis in experimental pancreas transplantation. These results indicate that IPC might increase I/R injury after pancreatic cold ischemia.

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Cell Death in Human Lung Transplantation: Apoptosis Induction in Human Lungs During Ischemia and After Transplantation

Cited by 169 publications

References 41 publications

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

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

Adult Respiratory Distress Syndrome and alveolar epithelium apoptosis: an histopathological and immunohistochemical study.

Ischemic preconditioning fails to improve microcirculation but increases apoptotic cell death in experimental pancreas transplantation

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