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Introduction: The occurrence of lung ischemia-reperfusion injury (LIRI) after lung transplantation results in primary graft dysfunction (PGD) in more than 50% of cases, which seriously affects the prognosis of recipients. Currently, donor lung protection is the focus of research on improving graft survival in lung transplant recipients. Dexmedetomidine (Dex) is a widely used general anesthesia adjuvant in clinical practice to alleviate ischemia-reperfusion injury in the lungs, liver, heart, kidneys, and brain. However, intravenous infusion of Dex can cause negative effects on the cardiovascular system. Inhaling nebulized Dex can directly act on the alveolar tissue and alleviate its cardiovascular inhibitory effect by reducing drug intake. This study aimed to investigate the effect of donor nebulized Dex inhalation on LIRI after lung transplantation in rats. Methods:We randomly allocated male Sprague–Dawley rats into donor groups inhaling nebulized Dex or saline 15 min preoperatively. The donor lung was refrigerated for 8 h before each single lung transplant. After 2 h of reperfusion of the transplanted lung, serum and transplanted lung tissue were collected. The wet-to-dry weight ratio of the lung tissue was measured, arterial blood gas was detected, and histopathology changes, oxidative stress, inflammatory reactions, and apoptosis were evaluated. Results: Pre-transplant inhalation of Dex through the donor’s lung reduced the injury of the transplanted lung, increased the levels of malondialdehyde and myeloperoxidase, and decreased the levels of superoxide dismutase and glutathione in the lung tissue. Moreover, nebulized Dex inhalation of the donor lung inhibited LIRI-induced tumor necrosis factor-α, interleukin-6, and inducible nitric oxide synthase expression, and also suppressed nuclear factor-kappa B phosphorylation. Nebulized Dex inhalation reduced the rate of cell apoptosis in the transplanted lung tissue by inhibiting the upregulation of Bax, downregulation of Bcl-2, and increase in caspase-3 lysis caused by LIRI. Conclusion: Inhalation of atomized Dex is a potential donor lung protection strategy, which can be used to reduce LIRI after lung transplantation and may be helpful to improve the occurrence of PGD and prognosis of lung transplant recipients.

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