Liver Graft Machine Perfusion: From History Perspective to Modern Approaches in Transplant Surgery.

The shortage of donor organs remains an unresolved issue in livertransplantation worldwide. Consequently, strategies for expanding the donor pool are currently being developed. Donors meeting extended criteria undergo thorough evaluation, as livers obtained from marginal donors yield poorer outcomes in recipients, including exacerbated reperfusion injury, acute kidney injury, early graft dysfunction, and primary nonfunctioning graft. However, the implementation of machine perfusion has shown excellent potential in preserving donor livers and improving their characteristics to achieve better outcomes for recipients. In this review, we analyzed the global experience of using machine perfusion in livertransplantation through the history ofthe development ofthis method to the latest trends and possibilities for increasing the number of liver transplants.

An Unexpected Partnership: Alexis Carrel, Charles Lindbergh, and Normothermic Machine Perfusion.

Organ transplantation is a triumph of modern medicine which represents a culmination of science and imagination, saving thousands of lives a year. However, transplantation is severely limited by suitable donor allografts. To expand the donor pool and make transplantation achievable for all, normothermic machine perfusion (NMP) is being employed more frequently. Normothermic machine perfusion involves the utilization of a device to approximate the physiology of the human body, preserve organs outside of the donor, and provide a dynamic assessment platform to determine organ suitability for transplantation. As NMP technology advances, it will soon be possible to genetically modify and actively repair these organs. Although its application to the field of transplantation is relatively new, the concept, foundation, and development of NMP can be traced back to the pioneering work of the surgeon-scientist, Alexis Carrel and the famous aviator, Charles Lindbergh in the 1930s. Their collaboration resulted in the Carrel-Lindbergh Perfusion device, an early perfusion device that was able to keep organs alive ex vivo for weeks and is most appropriately viewed as a precursor to modern machine perfusion technologies. As NMP technology becomes more advanced and refined, it is important to acknowledge the historical context in which these technologies emerged.

Pumping new life into old ideas: Preservation and rehabilitation of the liver using ex situ machine perfusion.

Recent advances in machine perfusion technology have reinvigorated the field of liver transplantation with the possibilities of vastly improving the efficiency and safety of the life-saving procedure. With this improved preservation technology, transplant surgeons are now able to use previously untransplantable donor livers without significantly compromising patient outcomes. Early clinical studies demonstrate the ability to extend preservation times and assess a graft's potential viability using normothermic machine perfusion, in addition to restoring the energy supply in donor livers by supporting metabolism through circulation of vital nutrients and blood-based oxygen carriers. Future endeavors for surgeons and scientists should focus on improving criteria to assess viability, optimizing protocols for perfusion research, investigating mechanisms of poor graft viability, and targeting these mechanisms with novel therapies to improve graft function prior to transplantation. Long-term goals include extending preservation times on the scale of days to weeks, enabling long-distance organ sharing, and establishing regional organ perfusion centers to streamline the procurement, perfusion, and transplantation process.

Preserving and perfusing the allograft pancreas: Past, present, and future.

The concept of organ preservation by perfusion dates back to the mid-19th century. Innovations since then have included temperature regulation, perfusion fluid composition and various pumping systems. Advances made in liver, heart and kidney machine preservation are now contributing to increased graft utilisation, assessment of graft viability and potentially improved graft survival. Pancreas transplantation has not benefitted to the same extent from the application of perfusion technology, although the need is just as great. This overview reviews current pancreas specific preservation techniques. We explore concepts, which include static cold storage, use of preservation solutions, the 'two-layer method', and machine perfusion. We also discuss ideas for future development. Narrative review of literature from inception to December 2017 using OVID interfaces searching EMBASE, Google Scholar, and MEDLINE databases. All studies relevant to pancreas perfusion and preservation were examined for clinical relevance with no exclusion criteria. Conference papers and presentations were also reviewed and included where appropriate. The application of recent advances in understanding in ischaemia-reperfusion as well as technical developments in machine preservation Ischaemia-reperfusion have the potential to improve organ utilisation, viability and outcome.

Organ preservation: from the past to the future.

Organ transplantation is the most effective therapy for patients with end-stage disease. Preservation solutions and techniques are crucial for donor organ quality, which is directly related to morbidity and survival after transplantation. Currently, static cold storage (SCS) is the standard method for organ preservation. However, preservation time with SCS is limited as prolonged cold storage increases the risk of early graft dysfunction that contributes to chronic complications. Furthermore, the growing demand for the use of marginal donor organs requires methods for organ assessment and repair. Machine perfusion has resurfaced and dominates current research on organ preservation. It is credited to its dynamic nature and physiological-like environment. The development of more sophisticated machine perfusion techniques and better perfusates may lead to organ repair/reconditioning. This review describes the history of organ preservation, summarizes the progresses that has been made to date, and discusses future directions for organ preservation.

Honoring 50 Years of Clinical Heart Transplantation in Circulation: In-Depth State-of-the-Art Review.

Heart transplantation has become a standard therapy option for advanced heart failure. The translation of heart transplantation from innovative experiments to long-term clinical success has married prescient insights with discipline and organization in the domains of surgical techniques, organ preservation, immunosuppression, organ donation and transplantation logistics, infection control, and long-term graft surveillance. This review explores the key milestones of the past 50 years of heart transplantation and discusses current challenges and promising innovations on the clinical horizon.

Historical perspectives in kidney transplantation: an updated review.

The present state of success in kidney transplantation, including its benefits to patients with end-stage renal failure, was achieved through relentless research, both in experimental animal models and human volunteers. Kidney transplantation has evolved during the past century thanks to various milestones in surgical techniques, immunology, immunosuppressive drugs, expansion of donor sources, organ preservation, transplant against immunological barriers (ABO blood group-incompatible and positive crossmatch transplants), and research on induction of tolerance, xenotransplants, and stem cell technology. Despite significant improvements in graft and patient survival, several issues still must be addressed to reduce the growing number of patients with kidney failure waiting to receive organs. This article provides an up-to-date review of the milestones in the history of kidney transplantation and highlights strategies to resolve current problems faced by patients and the transplant community.

Persufflation (gaseous oxygen perfusion) as a method of heart preservation.

Persufflation (PSF; gaseous oxygen perfusion) is an organ preservation technique with a potential for use in donor heart preservation. Improved heart preservation with PSF may improve outcomes by maintaining cardiac tissue quality in the setting of longer cold ischemia times and possibly increasing the number of donor hearts available for allotransplant. Published data suggests that PSF is able to extend the cold storage times for porcine hearts up to 14 hours without compromising viability and function, and has been shown to resuscitate porcine hearts following donation after cardiac death. This review summarizes key published work on heart PSF, including prospective implications and future directions for PSF in heart transplantation. We emphasize the potential impact of extending preservation times and expanding donor selection criteria in heart allotransplant. Additionally, the key issues that need to be addressed before PSF were to become a widely utilized preservation strategy prior to clinical heart transplantation are summarized and discussed.

[The 50th anniversary of the first liver transplantation: from myth to reality. Tributes to Thomas Starzl, 2012 Lasker Prize]. / Le cinquantenaire de la première transplantation hépatique: du mythe à la réalité. Hommages à Thomas Starzl, Prix Lasker 2012.

Chemical immunosuppression and the reversal of rejection permit to develop kidney transplantation and were incitative to start liver transplantation in 1963. However, the difficulties were many: wrong operative indications, inadequate immunosuppression, difficulty of etiologic diagnosis of jaundice, poor preservation of the graft. Cyclosporine was the key-step of the success.

[Serendipity, beneficial error, and chance in the development of kidney transplantation]. / Le hasard, l'erreur profitable, la chance dans le développement de la transplantation renale.

Serendipity played an essential role in two major developments of organ transplantation: the method of continuous hypothermic perfusion of the kidney and the introduction of ciclosporin in the clinical setting. An erroneous reasoning lead to the creation of an efficient preservation fluid: Collins's solution. However, these investigations would have failed without the open-mindedness and the tenacity of the clinicians.

Armand M. Karow, Jr.: Looking back.

Armand Karow, Jr. was a devoted scholar of cryobiology who was responsible for the creation of landmark books and many unique observations. Driven into cryobiology by a fascination with organ cryopreservation that dated from his high school days, Karow carried out or contributed to research on the cryopreservation of hearts, kidneys, pancreatic islets, and reproductive cells and tissues. His interests included not only conventional issues in cryobiology such as cryoprotectant permeation kinetics, theories of freezing injury in cells and tissues, and electromagnetic warming of large organs, but also more esoteric questions such as the limits of tolerance of mammalian organs to high pressures, the role of molecular hydration in cell viability, the pharmacological effects of cryoprotectants (which he frequently referred to as drugs), the limits of cryoprotectant tolerance at higher temperatures, and low temperature pharmacology. A look back at some of the discoveries made by Karow and his colleagues reveals many interesting leads whose further investigation could continue to provide valuable new insights in the future.

[Anatomical specimens and surgical instruments in old Dresden]. / Praeparata anatomica und Instrumenta medici im alten Dresden.

Passionate collectors of anatomical specimens, curiosities and surgical instruments the electors of Saxony between 1560 and 1748 founded great collections of this matter. They struggled for knowledge of nature, of the human body and of diseases. The exhibits were used by members of the court, by citizens and by the students of the first surgical school of Dresden, the Collegium medico-chirurgicum, and its successor. A selection of human and animal bones, fetuses, specimens in alcohol, abnormalities and medical instruments are described by original papers. The whole collection of preparations and old instruments was lost by being given away, fire and wars.