Mechanisms of lung ischemia-reperfusion injury

Abstract

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.

Size and targeting to PECAM vs ICAM control endothelial delivery, internalization and protective effect of multimolecular SOD conjugates

“…It has long been known that ROS released from activated leukocytes attack endothelium from the milieu [9]. More recently, it has been found, however, that ROS produced by endothelium itself in response to pathological stimuli play an important role in the pathogenesis of inflammation and ischemia-reperfusion [2, 10, 11]. In particular, cytokines activate NADPH-oxidase in endothelial endosomes to flux superoxide in the lumen of these vesicles and local intracellular surplus of this ROS ignites an "autocrine" signaling leading to pro-inflammatory endothelial changes [11-13].…”

Efeitos da suplementação com creatina na lesão de isquemia e reperfusão após transplante pulmonar unilateral em ratos

“…Não existem, ainda, agentes terapêuticos utilizados para prevenir a lesão de IR, sendo que as estratégias de tratamento estão limitadas aos cuidados de suporte (Laubach & Sharma, 2016).…”

“…Assim, a compreensão dos mecanismos celulares e moleculares da lesão IR pulmonar é fundamental para a tradução desses esforços de pesquisa em aplicação clínica (Laubach & Sharma, 2016).…”

“…No entanto, pode ocorrer a "inflamação estéril" em condições não infecciosas, incluindo traumatismo, lesão induzida quimicamente ou isquemias (Chen & Nunes, 2010;Laubach & Sharma, 2016). Nestes casos, a ativação do sistema imune inato promove a inflamação.…”

“…Nestes casos, a ativação do sistema imune inato promove a inflamação. No transplante de pulmão, a isquemia do órgão e a reperfusão subsequente são inevitáveis e, geralmente, conduzem à inflamação aguda e estéril após o transplante, chamada de lesão de isquemia e reperfusão (Laubach & Sharma, 2016).…”