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Organs


Advancements in human organ transplant surgery have been curtailed by the problem of donor organ acquisition and the noticeable unsuccessful quest for an ideal universal preservation solution for the storage and transportation of individual and multiple human donor organs over international distances. Currently, donor organ preservation solutions are designed to preserve organs suspended in an inanimate, non-functional state under 'cold' conditions for limited time periods of 4 – 24 hours which have proved restrictive for their delivery to recipient patients world-wide. In addition, the surgeon's inability to assess the functionality of donor organs has resulted in them being termed 'marginal' and unsuitable for transplantation.

Historically, the design of organ preservation solutions dates back to the hypothesis proposed by the French physician, Claude Bernard (1872), who purported that to maintain the integrity of the organs comprising the whole (person) one should ensure that the extracellular fluid environment surrounding all the cells and tissues of every organ should be balanced in all respects. Sadly, current human organ preservation solutions are derived from the basic salt solution formulations of Locke (1901), Tyrodes (1910) and Hanks (1948) and adopt, erroneously, intracellular sodium and potassium ion concentrations as proposed by Krebs (1950). A correct interpretation of Bernard's hypothesis necessitates that the every cell, tissue and organ be subtended by an extracellular (serum) fluid composition to preserve metabolic homeostasis and a natural biophysical environment.

The design of a universal preservation fluid is complicated by the fact that subtle biochemical differences exist between different types of organs which could influence preservation quality. Indeed, factors such as oedema formation, loss of membrane selective permeability, substrate depletion, are often the result of a failure to recognise the importance of an optimal physiological environment so precipitating the irreversible loss of physiological function upon subsequent reperfusion and/or re-implantation.

It has proved beneficial, in comparison to other preservation formulations, that the natural, auto-regulatory processes observed in all cell types, tissues and organs be addressed in the composition of AQIX® RS-I in order to achieve the status of a universal body perfusion fluid, while also serving as a preservation solution for use with different human cells, tissues and organs that could be maintained both inside (in vivo) and outside (ex vivo) the human body.

To this end, AQIX® RS-I was designed to be isosmotic and isoioinic to human serum and interstitial fluid and has not necessitated the inclusion of colloids, as have other preservation solutions, for the formulation has acknowledged that the cell membrane lies in continuity with a 99% gelatinous interstitial phase so providing natural colloidal buffering to excess ion and water exchange across the cell membrane so precluding the incidence of tissue swelling (oedema). An additional beneficial action of AQIX® RS-I, in comparison to commercial, preservation solutions, has been the innovation of a superior pH buffering system based on the natural, α-stat pH buffering afforded by the imidazole groups within haemoglobin molecules.

Upon consideration of the data published to date (see, www.aqix.com), AQIX® RS-I has been shown to be superior to conventional solutions in being able to preserve under normothermic conditions, (i) the bodily functions of intravenously perfused rat and pig models, (ii) functionality of ex vivo perfused rat, rabbit, guinea pig, pig and human tissues and organs, (iii) reanimate cadaver, donor 'marginal' organs for use in bioassay investigations to evaluate new drug design, and lastly (iv) as a donor organ 'flush' fluid that facilitates better function following transplantation. The Consortium for Organ Preservation in Europe (COPE) has adopted AQIX® RS-I as the basic fluid composition in their quest to improve donor organ transplant technology in 2013-16.