Background:Ex vivo lung perfusion(EVLP)has emerged as a critical technique for lung preservation and evaluation prior to transplantation.While conventional rat EVLP systems utilize closed-loop dual cannulation of pulm...Background:Ex vivo lung perfusion(EVLP)has emerged as a critical technique for lung preservation and evaluation prior to transplantation.While conventional rat EVLP systems utilize closed-loop dual cannulation of pulmonary artery(PA)and vein,the effect of the simplified model using single PA cannulation with passive venous drainage is unknown.Methods:We developed two EVLP models in rats:a semi-closed circuit with PA-only cannulation and left atrial incision for passive venous drainage(SC-EVLP),and a closed circuit employing both arterial and venous cannulation(C-EVLP).Donor lungs were perfused for a defined duration and subsequently orthotopically transplanted.We evaluated pulmonary function parameters,histopathological injury scores,inflammatory cytokine levels,and apoptotic marker expression at the end of perfusion and posttransplantation.Results:Compared to the conventional EVLP,the SC-EVLP group exhibited significantly lower PA pressure and improved dynamic lung compliance throughout perfusion.Although the levels of tumor necrosis factor-αin the perfusate were higher in the SC-EVLP group,other cytokine levels in the perfusate and bronchoalveolar lavage fluid exhibited no significant differences.Pulmonary edema was reduced in the SC-EVLP group,as indicated by a lower lung wet-to-dry ratio.After transplantation,lungs from the SC-EVLP group exhibited lower histological injury scores,reduced apoptosis,and decreased serum cytokine levels,suggesting attenuated inflammation and tissue damage.Conclusions:In a rat model,single PA cannulation with passive venous drainage reduced pulmonary edema during EVLP and reduced lung injury and systemic inflammation after transplantation.展开更多
Lung transplantation is the only definitive ther-apy for end-stage pulmonary disease.Less than 20%of offered lungs are successfully transplanted due to a limited ischemic time window and poor donor lung quality man-ife...Lung transplantation is the only definitive ther-apy for end-stage pulmonary disease.Less than 20%of offered lungs are successfully transplanted due to a limited ischemic time window and poor donor lung quality man-ifested by pulmonary edema,hypoxia,or trauma.Therefore,poor donor organ recovery and utilization are significant barriers to wider implementation of the life-saving therapy of transplantation.While ischemia reperfusion injury(IRI)is often identified as the underlying molecular insult leading to immediate poor lung function in the post-operative period,this injury encompasses several pathways of cellular injury in addition to the recruitment of the innate immune system to the site of injury to propagate this inflammatory cascade.Pyroptosis is a central molecular inflammatory pathway that is the most significant contributor to injury in this early post-operative phase.Pyroptosis is another form of pro-grammed cell death and is often associated with IRI.The mitigation of pyroptosis in the early post-operative period following lung transplantation is a potential novel way to prevent poor allograft function and improve outcomes for all recipients.Here we detail the pyroptotic pathway,its importance in lung transplantation,and several therapeutic modalities that can mitigate this harmful inflammatory pathway.展开更多
基金Key Science and Technology Program of Shaanxi Province,Grant/Award Number:2024SF2-GJHX-45National Natural Science Foundation of China,Grant/Award Number:82472191The Natural Science Foundation of Shaanxi Province,Grant/Award Number:2024JC-ZDXM-49。
文摘Background:Ex vivo lung perfusion(EVLP)has emerged as a critical technique for lung preservation and evaluation prior to transplantation.While conventional rat EVLP systems utilize closed-loop dual cannulation of pulmonary artery(PA)and vein,the effect of the simplified model using single PA cannulation with passive venous drainage is unknown.Methods:We developed two EVLP models in rats:a semi-closed circuit with PA-only cannulation and left atrial incision for passive venous drainage(SC-EVLP),and a closed circuit employing both arterial and venous cannulation(C-EVLP).Donor lungs were perfused for a defined duration and subsequently orthotopically transplanted.We evaluated pulmonary function parameters,histopathological injury scores,inflammatory cytokine levels,and apoptotic marker expression at the end of perfusion and posttransplantation.Results:Compared to the conventional EVLP,the SC-EVLP group exhibited significantly lower PA pressure and improved dynamic lung compliance throughout perfusion.Although the levels of tumor necrosis factor-αin the perfusate were higher in the SC-EVLP group,other cytokine levels in the perfusate and bronchoalveolar lavage fluid exhibited no significant differences.Pulmonary edema was reduced in the SC-EVLP group,as indicated by a lower lung wet-to-dry ratio.After transplantation,lungs from the SC-EVLP group exhibited lower histological injury scores,reduced apoptosis,and decreased serum cytokine levels,suggesting attenuated inflammation and tissue damage.Conclusions:In a rat model,single PA cannulation with passive venous drainage reduced pulmonary edema during EVLP and reduced lung injury and systemic inflammation after transplantation.
基金supported through the National Institute of Health (NIH)grant R01 HL143000 and serves on the Clinical Events Committee of Trans Medics OCSsupported by the NIH grants:HL153876,EY030621,EY032583 and the American Heart Association grant:23TPA1142638supported through the Jewel and Frank Benson Family Endowment and The Jewel and Frank Benson Research Professorship at The Ohio State University.
文摘Lung transplantation is the only definitive ther-apy for end-stage pulmonary disease.Less than 20%of offered lungs are successfully transplanted due to a limited ischemic time window and poor donor lung quality man-ifested by pulmonary edema,hypoxia,or trauma.Therefore,poor donor organ recovery and utilization are significant barriers to wider implementation of the life-saving therapy of transplantation.While ischemia reperfusion injury(IRI)is often identified as the underlying molecular insult leading to immediate poor lung function in the post-operative period,this injury encompasses several pathways of cellular injury in addition to the recruitment of the innate immune system to the site of injury to propagate this inflammatory cascade.Pyroptosis is a central molecular inflammatory pathway that is the most significant contributor to injury in this early post-operative phase.Pyroptosis is another form of pro-grammed cell death and is often associated with IRI.The mitigation of pyroptosis in the early post-operative period following lung transplantation is a potential novel way to prevent poor allograft function and improve outcomes for all recipients.Here we detail the pyroptotic pathway,its importance in lung transplantation,and several therapeutic modalities that can mitigate this harmful inflammatory pathway.
