Abdominal Organ Preservation Solutions in the Age of Machine Perfusion

Abstract

The past decade has been the foreground for a radical revolution in the field of preservation in abdominal organ transplantation. Perfusion has increasingly replaced static cold storage as the preferred and even gold standard preservation method for marginal-quality organs. Perfusion is dynamic and offers several advantages in comparison with static cold storage. These include the ability to provide a continuous supply of new metabolic substrates, clear metabolic waste products, and perform some degree of organ viability assessment before actual transplantation in the recipient. At the same time, the ongoing importance of static cold storage cannot be overlooked, in particular when it comes to logistical and technical convenience and cost, not to mention the fact that it continues to work well for the majority of transplant allografts. The present review article provides an overview of the fundamental concepts of organ preservation, providing a brief history of static cold preservation and description of the principles behind and basic components of cold preservation solutions. An evaluation of current evidence supporting the use of different preservation solutions in abdominal organ transplantation is provided. As well, the range of solutions used for machine perfusion of abdominal organs is described, as are variations in their compositions related to changing metabolic needs paralleling the raising of the temperature of the perfusate from hypothermic to normothermic range. Finally, appraisal of new preservation solutions that are on the horizon is provided.

A Single Preservation Solution for Static Cold Storage and Hypothermic Oxygenated Perfusion of Marginal Liver Grafts: A Preclinical Study

“…4,5,25 To date, most published studies on HOPE in LT use Belzer MPS and an additional preservation solution for SCS. 3 Belzer MPS has 2 major drawbacks in the context of cold perfusion of marginal liver grafts. First, this solution has been designed for kidney perfusion and contains HES as the main oncotic agent resulting in a high viscosity (Table 1).…”

“…Perfusion with a high-viscosity solution may increase shear stress under hypothermic conditions, especially in marginal liver grafts with endothelial damage and sinusoidal microthrombi. 3,26 Second, because Belzer MPS is not suited for SCS, there is a need to use a different preservation solution for SCS, leading to a mix of different preservation solutions. Indeed, the sequential use of UW and Belzer MPS exposes the graft to a solution with an intracellular-like electrolyte composition followed by a solution with an extracellular-like electrolyte composition.…”

“…1 Although preservation with static cold storage (SCS) has shown excellent results in benchmark transplant scenarios, the currently used preservation solutions have been developed more than a decade ago and have thus not been tailored to the requirements of preserving marginal grafts. 2,3 More importantly, although the use of hypothermic oxygenated perfusion (HOPE) has been shown to improve outcomes in both extended criteria DCD and donation after brain death LT, there is no preservation solution available to date specifically designed for the use during HOPE. [3][4][5][6] With this in mind, a novel preservation solution was designed for SCS and cold perfusion of marginal liver grafts.…”

“…2,3 More importantly, although the use of hypothermic oxygenated perfusion (HOPE) has been shown to improve outcomes in both extended criteria DCD and donation after brain death LT, there is no preservation solution available to date specifically designed for the use during HOPE. [3][4][5][6] With this in mind, a novel preservation solution was designed for SCS and cold perfusion of marginal liver grafts. This study aims to test this novel single preservation solution (IGL2) in a preclinical model of hepatic IRI and compare it with the current gold standard of 2 different preservation solutions for static and dynamic preservation.…”

Metabolomic Analysis, Perfusate Composition, and Pseudo-physiology of the Isolated Liver During Ex Situ Normothermic Machine Perfusion

“…Aside from issues related to hepatic artery perfusion (continuous as opposed to pulsatile) and inclusion of short-duration membrane oxygenators, another common shortcoming of liver NMP for extended perfusion preservation is that it supplies little more than heparinized red blood cells diluted in colloid and supplemented continuously with a limited array of nutrients and electrolytes, insulin, antimicrobials, and a single bile acid to increase bile flow. 1 Although normothermic liver perfusion performed in this manner may keep a graft viable over a relatively brief period, it creates a pseudo-physiological situation, in which some liver functions may be maintained but others are notably altered.…”