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Normothermic Ex-vivo Liver Perfusion and the Clinical Implications for Liver Transplantation

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Journal of Clinical and Translational Hepatology 2018年第3期6卷 276-282页

作者： Clifford Akateh Eliza W.Beal bryan a.whitson Sylvester M.Black General and Gastrointestinal Surgery Department of SurgeryThe Ohio State University Wexner Medical CenterColumbusOhioUSA Division of Cardiac Surgery Department of SurgeryThe Ohio State University Wexner Medical CenterColumbusOhioUSA Division of Transplant Surgery Department of SurgeryThe Ohio State University Wexner Medical CenterColumbusOhioUSA

Despite significant improvements in outcomes after liver trans-plantation,many patients continue to die on the waiting list,while awaiting an available organ for *** shortage is not only due to an inadequate number of available organs,but also the inability to adequately assess and evaluate these organs prior to *** the last few decades,ex-vivo perfusion of the liver has emerged as a useful technique for both improved organ preservation and assessment of organs prior to *** animal studies have shown the superiority of ex-vivo perfusion over cold static ***,these studies have not,necessa-rily,been translatable to human *** animal studies have been essential in understanding and improving this ***,these results have yet to be translated into clinical use.A few Phase 1 clinical trials have shown promise and confirmed the viability of this ***,more robust studies are needed before ex-vivo liver perfusion can be widely accepted as the new clinical standard of organ ***,we aimed to review al relevant large and smal animal research,as well as human liver studies on normother-mic ex-vivo perfusion,and to identify areas of deficiency and opportunities for future research endeavors.

关键词： Liver Transplantation Ex-vivo perfusion

Animal models of ex vivo lung perfusion as a platform for transplantation research

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World Journal of Experimental Medicine 2014年第2期4卷 7-15页

作者： Kevin Nelson Christopher Bobba Samir Ghadiali Don Hayes Jr Sylvester M Black bryan a.whitson Department Biomedical Engineering The Ohio State UniversityColumbusOH 43210United States Department of Internal Medicine Division of PulmonaryAllergyand Critical Care and Sleep MedicineThe Ohio State University Wexner Medical Center The Ohio State University Department of Pediatrics Nationwide Children’s HospitalColumbusOH 43210United States Department of Surgery Division of TransplantationColumbusOH 43210United States Department of Surgery Division of Cardiac SurgeryThe Collaboration for Organ PerfusionProtectionEngineering and Regeneration LaboratoryThe Ohio State University Wexner Medical CenterColumbusOH 43210United States

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.

关键词： Ex vivo lung perfusion Transplantation Rat Porcine Small animal Large animal Model Ex vivo lung perfusion

Organ assessment and repair centers: The future of transplantation is near

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World Journal of Transplantation 2014年第2期4卷 40-42页

作者： bryan a.whitson Sylvester M Black Division of Cardiac Surgery The Collaboration for Organ PerfusionProtectionEngineering and Regeneration (COPPER) LaboratoryThe Ohio State University Wexner Medical CenterColumbusOH 43210United States Division of Transplantation The Collaboration for Organ PerfusionProtectionEngineering and Regeneration (COPPER) LaboratoryThe Ohio State University Wexner Medical CenterColumbusOH 43210United States

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.

关键词： Organ transplantation Ex vivo organ perfusion Lung Liver Kidney Heart

Outcomes of continuous flow ventricular assist devices

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World Journal of Surgical Procedures 2014年第1期4卷 1-8页

作者： Shelly Bansal Chittoor B Sai-Sudhakar bryan a.whitson Division of Thoracic Transplantation Department of Cardiothoracic Surgery University of Pittsburgh Pittsburgh PA 15260 United States Division of Cardiac Surgery Department of Surgery The Ohio State University Columbus OH 43210 United States Division of Cardiac Surgery The Collaboration for Organ Perfusion Protection Engineering and Regeneration (COPPER) Laboratory The Ohio State University Wexner Medical Center Columbus OH 43210 United States

Heart transplantation is commonplace, the supply is limited. Many exciting changes in the field of mechanical circulatory support have occurred in the past few years, including the axial flow pump. Left ventricular assist device(LVAD) therapy is ever evolving. As the use of LVAD therapy increases it is important to understand the indications, surgical considerations and outcomes.

关键词： Left ventricular assist device Axial flow Mechanical circulatory support Heart failure Continuous flow

Preservation solutions used during abdominal transplantation:Current status and outcomes

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World Journal of Transplantation 2015年第4期5卷 154-164页

作者： Nicholas Latchana Joshua R Peck bryan a.whitson Mitchell L Henry Elmahdi A Elkhammas Sylvester M Black Department of Surgery the Ohio State University Wexner Medical Department of Internal Medicine Division of Gastroenterologythe Ohio State University Wexner Medical Center Department of Surgery Division of Cardiac Surgerythe Ohio State University Wexner Medical Center Department of Surgery Division of Transplantationthe Ohio State University Wexner Medical Center

Organ preservation remains an important contributing factor to graft and patient outcomes. During donor organ procurement and transportation, cellular injury is mitigated through the use of preservation solutions in conjunction with hypothermia. Various preservation solutions and protocols exist with widespread variability among transplant centers. In this review of abdominal organ preservation solutions, evolution of transplantation and graft preservation are discussed followed by classification of preservation solutions according to the composition of electrolytes, impermeants, buffers, antioxidants, and energy precursors. Lastly, pertinent clinical studies in the setting of hepatic, renal, pancreas, and intestinal transplantation are reviewed for patient and graft survival as well as financial considerations. In liver transplants there may be some benefit with the use of histidine-tryptophan-ketoglutarate(HTK) over University of Wisconsin solution in terms of biliary complications and potential cost savings. Renal grafts may experience increased initial graft dysfunction with the use of Euro-Collins thereby dissuading its use in support of HTK which can lead to substantial cost savings. University of Wisconsin solution and Celsior are favored in pancreas transplants given the concern for pancreatitis and graft thrombosis associated with HTK. No difference was observed with preservation solutions with respect to graft and patient survival in liver, renal, and pancreas transplants. Studies involving intestinal transplants are sparse but University of Wisconsin solution infused intraluminally in combination with an intra-vascular washout is a reasonable option until further evidence can be generated. Available literature can be used to ameliorate extensive variation across centers while potentially minimizing graft dysfunction and improving associated costs.

关键词： Graft preservation Kidney Liver Pancreas Intestine

Caval reconstruction techniques in orthotopic liver transplantation

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World Journal of Surgical Procedures 2015年第1期5卷 41-57页

作者： Eliza W Beal Shaylyn C Bennett bryan a.whitson Elmahdi A Elkhammas Mitchell L Henry Sylvester M Black Department of Surgery the Ohio State University Wexner Medical Center Division of Cardiothoracic Surgery Department of Surgerythe Ohio State University Wexner Medical Center Division of Transplantation Surgery Department of Surgerythe Ohio State University Wexner Medical Center

There are several caval reconstruction techniques currently in use for orthotopic liver transplantation. These include caval replacement or the conventional technique, performed with or without venovenous bypass, piggyback technique with anastomosis with two or three hepatic veins with or without cavotomy and modifications of the piggyback technique including end-to-side and side-to-side cavocaval anastomosis. There are few randomized controlled trials comparing the use of these techniques and our knowledge of their comparability is based on a few multi- and many single-center retrospective and prospective reviews. Although there are advantages and disadvantages for each technique, it is advisable that the surgeon perform the technique with which they have the most the experience and at which they are the most skilled as excellent outcomes can be obtained with any of the caval reconstruction options discussed.

关键词： Caval replacement Piggyback technique Conventional liver transplant Standard liver transplant Venovenous bypass Portocaval shunt

Mechanical circulatory support in lung transplantation: Cardiopulmonary bypass, extracorporeal life support, and ex-vivo lung perfusion

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World Journal of Respirology 2015年第2期5卷 78-92页

作者： Shaylyn C Bennett Eliza W Beal Curtis A Dumond Thomas Preston Jim Ralston Amy Pope-Harman Sylvester Black Don Hayes Jr bryan a.whitson Department of Surgery the Ohio State University Wexner Medical Center Division of Cardiothoracic Surgery Department of Surgerythe Ohio State University Wexner Medical Center Department of Cardiovascular Perfusion and ECMO Nationwide Children’s Hospital Department of Perfusion the Ohio State University Wexner Medical Center Division of Pulmonary AllergyCritical Care and Sleep Medicinethe Ohio State University Wexner Medical Center Division of Transplantation Surgery Department of Surgerythe Ohio State University Wexner Medical Center Department of Pediatric Pulmonology Nationwide Children’s Hospital

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.

关键词： Lung transplant Cardiopulmonary bypass Extracorporeal membrane oxygenation Extracorporeal life support Extracorporeal lung assist Interventional lung assist Ex-vivo lung perfusion