Ex vivo lung perfusion(EVLP) is a powerful experimental model for isolated lung research. EVLP allows for the lungs to be manipulated and characterized in an external environment so that the effect of specific ventila...Ex vivo lung perfusion(EVLP) is a powerful experimental model for isolated lung research. EVLP allows for the lungs to be manipulated and characterized in an external environment so that the effect of specific ventilation/perfusion variables can be studied independent of other confounding physiologic contributions. At the same time,EVLP allows for normal organ level function and real-time monitoring of pulmonary physiology and mechanics. As a result,this technique provides uniqueadvantages over in vivo and in vitro models. Small and large animal models of EVLP have been developed and each of these models has their strengths and weaknesses. In this manuscript,we provide insight into the relative strengths of each model and describe how the development of advanced EVLP protocols is leading to a novel experimental platform that can be used to answer critical questions in pulmonary physiology and transplant medicine.展开更多
Normothermic ex vivo lung perfusion(NEVLP)has emerged as a modernized organ preservation technique that allows for detailed assessment of donor lung function prior to transplantation.The main goal of this study was to...Normothermic ex vivo lung perfusion(NEVLP)has emerged as a modernized organ preservation technique that allows for detailed assessment of donor lung function prior to transplantation.The main goal of this study was to identify potential biomarkers of lung function and/or injury during a prolonged(19 h)NEVLP procedure using in vivo solid-phase microextraction(SPME)technology followed by liquid chromatography-high resolution mass spectrometry(LC-HRMS).The use of minimally invasive in vivo SPME fibers for repeated sampling of biological tissue permits the monitoring and evaluation of biochemical changes and alterations in the metabolomic profile of the lung.These in vivo SPME fibers were directly introduced into the lung and were also used to extract metabolites(on-site SPME)from fresh perfusate samples collected alongside lung samplings.A subsequent goal of the study was to assess the feasibility of SPME as an in vivo method in metabolomics studies,in comparison to the traditional inlab metabolomics workflow.Several upregulated biochemical pathways involved in pro-and antiinflammatory responses,as well as lipid metabolism,were observed during extended lung perfusion,especially between the 11th and 12th hours of the procedure,in both lung and perfusate samples.However,several unstable and/or short-lived metabolites,such as neuroprostanes,have been extracted from lung tissue in vivo using SPME fibers.On-site monitoring of the metabolomic profiles of both lung tissues through in vivo SPME and perfusate samples on site throughout the prolonged NEVLP procedure can be effectively performed using in vivo SPME technology.展开更多
Lung transplant is the standard of care for patients with end-stage lung disease refractory to medical management. There is currently a critical organ shortage for lung transplantation with only 17% of offered organs ...Lung transplant is the standard of care for patients with end-stage lung disease refractory to medical management. There is currently a critical organ shortage for lung transplantation with only 17% of offered organs being transplanted. Of those patients receiving a lung transplant, up to 25% will develop primary graft dysfunction, which is associated with an 8-fold increase in 30-d mortality. There are numerous mechanical lung assistance modalities that may be employed to help combat these challenges. We will discuss the use of mechanical lung assistance during lung transplantation, as a bridge to transplant, as a treatment for primary graft dysfunction, and finally as a means to remodel and evaluate organs deemed unsuitable for transplant, thus increasing the donor pool, improving survival to transplant, and improving overall patient survival.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
Solid organ transplantation is limited by suitable donor organ availability and the geographic limitations that lead to prolonged ischemic times. Ex vivo organ perfusion is an evolving technology that enables assessme...Solid organ transplantation is limited by suitable donor organ availability and the geographic limitations that lead to prolonged ischemic times. Ex vivo organ perfusion is an evolving technology that enables assessment of organ function prior to transplantation. As a byproduct, overall out of body organ times are able to be extended. The future implications organ assessment and repair centers utilizing this technology are discussed.展开更多
文摘Ex vivo lung perfusion(EVLP) is a powerful experimental model for isolated lung research. EVLP allows for the lungs to be manipulated and characterized in an external environment so that the effect of specific ventilation/perfusion variables can be studied independent of other confounding physiologic contributions. At the same time,EVLP allows for normal organ level function and real-time monitoring of pulmonary physiology and mechanics. As a result,this technique provides uniqueadvantages over in vivo and in vitro models. Small and large animal models of EVLP have been developed and each of these models has their strengths and weaknesses. In this manuscript,we provide insight into the relative strengths of each model and describe how the development of advanced EVLP protocols is leading to a novel experimental platform that can be used to answer critical questions in pulmonary physiology and transplant medicine.
基金the Canadian Institute of Health Research(CIHR)-Natural Sciences and Engineering Research Council(NSERC)of the Canada Collaborative Health Research Projects program for their financial support(Grant No.:355935)the Natural Sciences and Engineering Research Council of Canada Industrial Research Chair(IRC)program.
文摘Normothermic ex vivo lung perfusion(NEVLP)has emerged as a modernized organ preservation technique that allows for detailed assessment of donor lung function prior to transplantation.The main goal of this study was to identify potential biomarkers of lung function and/or injury during a prolonged(19 h)NEVLP procedure using in vivo solid-phase microextraction(SPME)technology followed by liquid chromatography-high resolution mass spectrometry(LC-HRMS).The use of minimally invasive in vivo SPME fibers for repeated sampling of biological tissue permits the monitoring and evaluation of biochemical changes and alterations in the metabolomic profile of the lung.These in vivo SPME fibers were directly introduced into the lung and were also used to extract metabolites(on-site SPME)from fresh perfusate samples collected alongside lung samplings.A subsequent goal of the study was to assess the feasibility of SPME as an in vivo method in metabolomics studies,in comparison to the traditional inlab metabolomics workflow.Several upregulated biochemical pathways involved in pro-and antiinflammatory responses,as well as lipid metabolism,were observed during extended lung perfusion,especially between the 11th and 12th hours of the procedure,in both lung and perfusate samples.However,several unstable and/or short-lived metabolites,such as neuroprostanes,have been extracted from lung tissue in vivo using SPME fibers.On-site monitoring of the metabolomic profiles of both lung tissues through in vivo SPME and perfusate samples on site throughout the prolonged NEVLP procedure can be effectively performed using in vivo SPME technology.
文摘Lung transplant is the standard of care for patients with end-stage lung disease refractory to medical management. There is currently a critical organ shortage for lung transplantation with only 17% of offered organs being transplanted. Of those patients receiving a lung transplant, up to 25% will develop primary graft dysfunction, which is associated with an 8-fold increase in 30-d mortality. There are numerous mechanical lung assistance modalities that may be employed to help combat these challenges. We will discuss the use of mechanical lung assistance during lung transplantation, as a bridge to transplant, as a treatment for primary graft dysfunction, and finally as a means to remodel and evaluate organs deemed unsuitable for transplant, thus increasing the donor pool, improving survival to transplant, and improving overall patient survival.
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.
文摘Solid organ transplantation is limited by suitable donor organ availability and the geographic limitations that lead to prolonged ischemic times. Ex vivo organ perfusion is an evolving technology that enables assessment of organ function prior to transplantation. As a byproduct, overall out of body organ times are able to be extended. The future implications organ assessment and repair centers utilizing this technology are discussed.
