Content area
Full text
1. Introduction
The prevention of preservation injury is crucial to accomplish the early recovery of cellular metabolism after transplantation and to avoid graft dysfunction. To bridge the timespan from the harvesting to the implantation in the recipient, the livers are stored in preservation solutions on melting ice at 0–4°C, allowing a safe preservation up to 12 h [1]. A cold ischemia longer than 12 h still implies a greater risk of graft dysfunction. Furthermore, the rising demand for transplantation triggers the use of the so-called extended criteria donors, which tolerate a period of cold ischemia even shorter than 12 hours [2].
Alteration of the energy metabolism is an important feature of preservation injury [3]. Hypothermia at 0–4°C is a key factor for organ preservation by reducing the cellular metabolic activity about 90–95% [4]. However, even at this low temperature, metabolism still requires 0.27 mol oxygen/min/g of liver [4], which is not provided by the current static storage. Oxygen is mainly taken up by mitochondria to allow the synthesis of adenosine triphosphate (ATP); therefore, the lack of oxygen results in failure of the respiratory chain and ATP can solely be generated through the anaerobic glycolysis. Once the cellular glycogen stores are consumed, ATP depletion rapidly ensues leading to a series of events which eventually cause irreversible cell injury and death [5].
In the last decade, experimental studies have shown that continuous perfusion of the liver during preservation can improve graft viability and challenge the limits of the current static storage [6–9]. However, several issues need to be clarified before the hypothermic machine perfusion (HMP) will reach the clinical application, including the type of preservation solution, the characteristics of perfusion dynamics, and the modalities of oxygen supply [4, 9]. Regarding the latter issue, oxygenation of the solution appears to be a typical double-edge condition: the oxygen supplied during cold ischemia should guarantee the ATP synthesis for the residual metabolic activity, but, at the same time, it might favor the generation of reactive oxygen species (ROS) leading to the exacerbation of cellular injury.
Treatment with hyperbaric oxygen is a method that employs exposure to 100% oxygen at a pressure above 1 atmosphere absolute (1 ATA) to promote tissue hyperoxygenation. In the setting of liver diseases, hyperbaric oxygen has been used to...