The Effect of Preservation Temperature on Liver, Kidney, and Pancreas Tissue ATP in Animal and Preclinical Human Models

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.

Organ Restoration With Normothermic Machine Perfusion and Immune Reaction

“…Branchereau et al demonstrated that whilst using a hypothermic oxygenated continuous circuit at 25 mmHg for 24 h, none of the pancreas grafts used in the study showed signs of, or produced markers of, cellular injury, oedema, or necrosis. The tissue level of adenosine triphosphate (ATP) is a long-established marker of graft viability and functionality and is universal for all solid organ transplants (22). ATP is also a marker of the viability of machine-perfusion treated grafts (23).…”

Experimental isolation and preservation of solid organs before transplantation: effects of pretreatment using four different molecules

“…The findings show that the re-introduction of tissue adenosine triphosphate (ATP) levels in the current method may be valuable for improving the viability assessment of organs that are harvested for transplantation. 36 These findings may help with future investigations. Our purpose was to investigate each of these molecules (erythropoetin, sildenafil, lazaroid, and octreotide), and based on the results, to design further studies.…”

Restoring Mitochondrial Function While Avoiding Redox Stress: The Key to Preventing Ischemia/Reperfusion Injury in Machine Perfused Liver Grafts?

“…The ischemic phase already primes the tissue for the subsequent damage [7]. Reducing equivalents are generated to provide electrons for RET, which are in turn required for mROS production upon subsequent reperfusion [9,12,13]. The predominant mitochondrial metabolite accumulating during ischemia is driven by the reverse operation of succinate dehydrogenase (SDH).…”

“…The temperature is low enough to achieve sufficient oxygenation without the implicit addition of an oxygen carrier, which enables the restoration of ATP levels. At the same time, the temperature is high enough to allow for the partial viability assessment of the organ [13,43,44].…”

“…Since ATP is depleted during ischemia, measurement of ATP tissue levels during MP is suggested to serve as a reliable mitochondrial function marker. During the preservation phase, the respective MP strategies contribute to the resynthesis of ATP, whereby the recovery of the energy status correlates with the functionality of the organ [13].…”