Abstract
The recent advances in machine perfusion (MP) technology involve settings ranging between hypothermic, subnormothermic, and normothermic temperatures. Tissue level adenosine triphosphate (ATP) is a long-established marker of viability and functionality and is universal for all organs. In the midst of a growing number of complex clinical parameters for the quality assessment of graft prior to transplantation, a revisit of ATP may shed light on the underlying reconditioning mechanisms of different perfusion temperatures in the form of restoration of metabolic and energy status. This article aims to review and critically analyse animal and preclinical human studies (discarded grafts) during MP of three abdominal organs (liver, kidney, and pancreas) in which ATP was a primary endpoint. A selective review of recent novel reconditioning approaches relevant to mitigation of graft ischaemia-reperfusion injury via MP and for different perfusion temperatures was also conducted. With a current reiterated interest for oxygenation during MP, a re-introduction of tissue ATP levels may be valuable for graft viability assessment prior to transplantation. Further studies may help delineate the benefits of selective perfusion temperatures on organs viability.
Highlights
If the organ is instead preserved with a dynamic preservation, there is the potential to resuscitate it and restore function, such as the recovery of metabolic energetic status in cell mitochondria, e.g., resynthesis of tissue adenosine triphosphate (ATP), reduction in reactive oxygen species (ROS), and inflammatory cytokines resulted from ischaemia-reperfusion injury (IRI)
This study presented a subnormothermic machine perfusion (SNMP) orthotopic liver transplantation model with oxygenated and supplemented cell culture medium as perfusate
While HOPE demonstrated potential in the restoration of metabolic energetic status and bile production of human discarded liver grafts, Westerkamp et al [21] argued that HOPE may not be as effective in the repair of existing hepatobiliary injuries, since there were no differences in the levels of injury markers such as aspartate aminotransferase (AST), ALT, and lactate dehydrogenase (LDH) when compared to the control group (NMP only)
Summary
Organ transplantation remains the most effective treatment of end-stage organ failure. A higher proportion of patients may suffer from early graft dysfunction or delayed graft function (DGF), prolonged hospital stay, and increased morbidity in general: Biliary complications in the case of liver [4], acute renal failure after kidney transplant [5], and the need for insulin therapy in the context of pancreas transplantation [6]. Even though SCS is logistically simpler, there is evidence of parenchymal damage by extended periods of ischaemia and lack of oxygen with the use of this modality. If the organ is instead preserved with a dynamic preservation, there is the potential to resuscitate it and restore function, such as the recovery of metabolic energetic status in cell mitochondria, e.g., resynthesis of tissue adenosine triphosphate (ATP), reduction in reactive oxygen species (ROS), and inflammatory cytokines resulted from ischaemia-reperfusion injury (IRI). Viability assessment is a possibility during ex vivo normothermic machine perfusion (NMP) at 37 ◦C, which facilitates the surveillance of perfusion parameters, histological and metabolic analysis of biopsy samples [7] for evaluation of the extent of graft tissue injury, prediction of post-transplantation graft function, and rate of survival
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