Methylene blue attenuates ischemia–reperfusion injury in lung transplantation

Abreu, Marcus da Matta; Pazetti, Rogério; Almeida, Francine Maria de; Correia, Aristides Tadeu; Parra, Edwin Roger; Silva, Laís Pereira da; Vieira, Rodolfo de Paula; Pêgo-Fernandes, Paulo Manuel; Jatene, Fábio Biscegli

doi:10.1016/j.jss.2014.07.043

Cited by 24 publications

(18 citation statements)

References 28 publications

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“…Recent studies have identified a variety of strategies including: 1) anti-oxidant strategies using free radical scavengers or inhibitors of oxidant-producing enzymes (e.g. methylene blue [36] or N-acetylcysteine [37]); 2) anti-inflammatory strategies using inhibitors of pro-inflammatory transcription factors (e.g. inhibitor of Egr-1 [27]) or inflammatory mediators (e.g.…”

Section: Strategies To Limit Ir Injurymentioning

confidence: 99%

Mechanisms of lung ischemia-reperfusion injury

Laubach

Sharma²

2016

Current Opinion in Organ Transplantation

192

191

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Purpose of review Lungs are extremely susceptible to injury, and despite advances in surgical management and immunosuppression, outcomes for lung transplantation are the worst of any solid organ transplant. The success of lung transplantation is limited by high rates of primary graft dysfunction (PGD) due to ischemia-reperfusion (IR) injury characterized by robust inflammation, alveolar damage and vascular permeability. This review will summarize major mechanisms of lung IR injury with a focus on the most recent findings in this area. Recent findings Over the past 18 months numerous studies have described strategies to limit lung IR injury in experimental settings, which often reveal mechanistic insight. Many of these strategies involved the use of various anti-oxidants, anti-inflammatory agents, mesenchymal stem cells, and ventilation with gaseous molecules. Further advancements have been achieved in understanding mechanisms of innate immune cell activation, neutrophil infiltration, endothelial barrier dysfunction, and oxidative stress responses. Summary Methods for prevention of PGD after lung transplant are urgently needed, and understanding mechanisms of IR injury is critical for the development of novel and effective therapeutic approaches. In doing so, both acute and chronic outcomes of lung transplant recipients will be significantly improved.

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Section: Strategies To Limit Ir Injurymentioning

confidence: 99%

Mechanisms of lung ischemia-reperfusion injury

Laubach

Sharma²

2016

Current Opinion in Organ Transplantation

192

191

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“…IL-6 is part of the TNF-α activated pro-inflammatory pathway that has been noted by several groups including our own to be a component of ischemia-reperfusion injury after lung transplant(16, 18–22). However, Farivar and colleagues demonstrated reduced endothelial disruption and neutrophil sequestration with recombinant IL-6 in a rat ischemia-reperfusion model of lung transplant highlighting the signal orchestration that can lead to both pro- and anti-inflammatory effects of this cytokine(23).…”

Section: Discussionmentioning

confidence: 70%

Airway pressure release ventilation during ex vivo lung perfusion attenuates injury

Mehaffey

Charles

Sharma

et al. 2017

The Journal of Thoracic and Cardiovascular Surgery

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Objective Critical organ shortages have resulted in Ex Vivo Lung Perfusion (EVLP) gaining clinical acceptance for lung evaluation and rehabilitation to expand the use of Donation after Circulatory Death (DCD) organs for lung transplantation. We hypothesized that an innovative use of airway pressure release ventilation (APRV) during EVLP improves lung function after transplantation. Methods Two groups (n=4 animals/group) of porcine DCD donor lungs were procured after hypoxic cardiac arrest and a 2-hour period of warm ischemia, followed by a 4-hour period of EVLP rehabilitation with either standard conventional volume-based ventilation or pressure-based APRV. Left lungs were subsequently transplanted into recipient animals and reperfused for 4 hours. Blood gases for PaO2/FiO2 ratios, airway pressures for calculation of compliance, and percent wet weight gain during EVLP and reperfusion were measured. Results APRV during EVLP significantly improved left-lung oxygenation at 2-hours (561.5±83.9 vs 341.1±136.1 mmHg) and 4-hours (569.1±18.3 vs 463.5±78.4 mmHg). Similarly, compliance was significantly higher at 2-hours (26.0±5.2 vs 15.0±4.6 mL/cmH2O) and 4-hours (30.6±1.3 vs 17.7±5.9 mL/cmH2O) after transplantation. Finally, APRV significantly reduced lung edema development on EVLP based on percentage weight gain (36.9±14.6 vs 73.9±4.9%). There was no difference in additional edema accumulation 4 hours after reperfusion. Conclusions Pressure-directed APRV ventilation strategy during EVLP improves rehabilitation of severely injured DCD lungs. After transplant these lungs demonstrate superior lung-specific oxygenation and dynamic compliance compared to lungs ventilated with standard conventional ventilation. This strategy, if implemented into clinical EVLP protocols, could advance the field of DCD lung rehabilitation to expand the lung donor pool.

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“…Lung transplantation has become an effective therapeutic option in the treatment of patients with various end-stage pulmonary diseases [1] such as chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, cystic fibrosis, bronchiectasis, and primary pulmonary hypertension [2] . Lung injury induced by ischemia-reperfusion (I/R) can lead to severe primary graft failure with about 60% mortality after lung transplantation [3][4][5] .…”

Section: Introductionmentioning

confidence: 99%

Ratlarda Akciğer Transplantasyonda Iskemi/Reperfüzyonun İndüklediği Oksidatif Hasara Karşı Viburnum opulus Meyve Ekstresinin Koruyucu Etkilerinin Araştırılması

Eken¹,

Yücel²,

Boşgelmez³

et al. 2017

Kafkas Univ Vet Fak Derg

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The aim of this study was to investigate the protective effect of Viburnum opulus L. fruit extract against ischemia/reperfusion (I/R)-induced oxidative stress during the lung transplantation. For this purpose, 30 female rats were firstly randomized to form of donor and recipients. After then, the rats were divided into three groups named as control, I/R, and V. opulus + I/R. Experimental rats were subjected to lung transplantation with ischemia followed by 2 h of reperfusion. Transplantation-related lung injury was evaluated by multiple parameters. A significant decrease was observed in the enzyme activities of superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT), and the levels of glutathione and total antioxidant status (TAS), whereas the levels of malondialdehyde (MDA), total oxidant status (TOS), and protein carbonyl were significantly increased in lung tissue samples of I/R group in comparison to the control group. However, treatment with V. opulus fruit extract resulted in significant reduction of MDA and protein carbonyl levels and increment of the antioxidant system. In conclusion, V. opulus fruit extract showed protective effects against I/R-induced oxidative stress during lung transplantation probably by the radical scavenging and antioxidant activity. Therefore, this fruit extract can be efficient in the prevention of I/R-related lung toxicity. Keywords: Oxidative Stress, Transplantation, Ischemia/Reperfusion, Antioxidant Ratlarda Akciğer Transplantasyonda Iskemi/Reperfüzyonun İndüklediği Oksidatif Strese Karşı Viburnum opulus L. Meyve Ekstresinin Koruyucu Etkisinin Araştırılması ÖzetBu çalışma, akciğer transplantasyonu sırasında iskemi/reperfüzyonun indüklediği oksidatif hasara karşı Viburnum opulus L. meyve ekstresinin koruyucu etkisini araştırmak amacıyla yapılmıştır. Bu amaçla, ilk olarak donör ve alıcı oluşturmak için 30 dişi rat rastgele seçildi. Daha sonra, ratlar kontrol, I/R ve V. opulus + I/R olarak adlandırılan üç gruba ayrıldı. Deneysel ratlara iskeminin ardından 2 saat reperfüzyon ile akciğer transplantasyonu yapıldı. Transplantasyon ile ilişkili akciğer hasarı, farklı parametrelerle incelendi. Kontrol grubu ile karşılaştırıldığında I/R grubunun akciğer doku örneklerinde süperoksit dismutaz (SOD), glutatyon peroksidaz (GPx) ve katalaz (CAT) enzim aktiviteleri, glutatyon ve total antioksidan durum (TAS) düzeylerinde önemli bir azalış, malondialdehit (MDA), total oksidan durum (TOS) ve protein karbonil düzeylerinde anlamlı artış belirlendi. Bununla birlikte, V. opulus meyve ekstresi ile uygulama sonrası MDA ve protein karbonil düzeylerinde önemli azalma ve antioksidan sistemde artma saptanmıştır. Sonuç olarak, akciğer transplantasyonu sırasında I/R'nin indüklediği oksidatif strese karşı V. opulus meyve ekstresinin muhtemel radikal temizleme ve antioksidan aktivitesi ile koruyucu etkilerinin olduğunu göstermiştir. Bu nedenle, bu meyve ekstresi I/R ilişkili akciğer hasarının önlenmesinde etkili olabilir.

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Methylene blue attenuates ischemia–reperfusion injury in lung transplantation

Cited by 24 publications

References 28 publications

Mechanisms of lung ischemia-reperfusion injury

Mechanisms of lung ischemia-reperfusion injury

Airway pressure release ventilation during ex vivo lung perfusion attenuates injury

Ratlarda Akciğer Transplantasyonda Iskemi/Reperfüzyonun İndüklediği Oksidatif Hasara Karşı Viburnum opulus Meyve Ekstresinin Koruyucu Etkilerinin Araştırılması

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