Abstract

Lung transplantation (LTx) is an effective treatment for end-stage lung disease. However, the shortage of donor lung causes the death of recipients in waiting list. In order to resolve the shortage of donor lung, non-beating heart donor (NBHD) lungs are used and ex vivo lung perfusion (EVLP) is performed in clinical setting. In this study, the effects of hydrogen gas known as antioxidant and anti-inflammatory gas on NBHD lungs were investigated during EVLP. Ten 40kg female pigs were randomly divided into control (group I, n=5) and study group (group II, n=5). The atrial fibrillation was induced by 9V electric shock and one hour of warm ischemic injury was induced by leaving them without any treatments after cardiac arrest. After flush using Perfadex solution, the harvested lungs were applied to EVLP system for 4 hours. Steen solution was used as perfusate. During EVLP, the lungs were ventilated with room air (0.2 of FiO2) in control group and 2% hydrogen gas in study group. Oxygen capacity ((PaO2- pulmonary artery of the left atrium PaO2) / FiO2), pulmonary vascular resistance (Pulmonary artery pressure-left atrium pressure) X 80/ pulmonary artery flow) and peak airway pressure were measured every hour for 4 hours of EVLP. After the EVLP, lung specimens were excised for measurement of the extent of p38, JNK, and ERK 1/2 phosphorylation and the expression of IL-1ß, IL-6, IL-8, and TNF-α. Pathologic evaluation was performed using lung injury severity score after H & E stain. Wet/dry ratio was examined. Oxygen capacity in study group was higher than in control group, which did not show a significant difference (p = 0.0862). However, pulmonary vascular resistance (p = 0.0111) and peak airway pressure (p = 0.0189) were significantly lower in study group. There was a tendency that the extents of phosphorylation of p38, JNK, and ERK 1/2 were lower in study group, but it was not statistically significant. The expressions of IL-1ß (p = 0.0317), IL-6 (p = 0.0159), IL-8 (p = 0.0195), and TNF-α (p = 0.0159) were all significantly lower in study group. Lung injury score (p = 0.0358) and wet/dry ratio (p = 0.040) were also lower in study group. The inhalation of hydrogen gas during EVLP improved the function of NBHD lung and it might increase the utilization of NHBD lung with warm ischemic injury.

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