A New Solution for Life Without Blood

Abstract

The faster neurological recovery of dogs treated with the "intracellular-type" maintenance solution supports the biochemical data showing the benefits of this type of blood substitute for extending the safe limits of hypothermic cardiac arrest procedures to > 3 hours.

Survey of Apoptosis After Hypothermic Storage of a Pancreatic β-Cell Line

“…[17][18][19][20][25][26][27][28] This base formulation of Unisol, which accounts for both biophysical and minimal biochemical requirements during low temperature storage, could then be used as a vehicle for the addition of other compounds that would facilitate survival, such as the addition of a caspase inhibitor like Q-VD-OPH. Unisol has also been evaluated for the preservation of a variety of cells, tissues, organs, and large mammals, 19,22,[29][30][31][32][33][34][35] but an analysis of apoptosis using Unisol has not previously been performed.…”

Hypothermic Blood Substitution: Special Considerations for Protection of Cells during ex vivo and in vivo Preservation

“…Recent research into the causative apoptotic and necrotic pathways responsible for low temperature induced DOCD has identified the contribution of multiple apoptotic pathways, including receptor and mitochondria induced apoptosis [28,30]. Investigations into these pathways, their progression, and their induction stressors has begun to facilitate new methods for improving preservation efficacy through the modulation of the cellular and molecular responses of a cell undergoing preservation (both hypothermic and cryopreservation) [1,23,28,[31][32][33][34]. The culmination of the cascade of interactive ischemic events is a tissue that is unable to resume its normal function upon restoration of its blood supply.…”

“…However, as mentioned above, it is well established that cooling induces detrimental changes to various properties of the blood that are not effectively ameliorated by simple hemodilution; these include dramatic increases in blood viscosity, coagulopathies and the deformability and clumping of erythrocytes which contribute significantly to the problem of multifocal blockage of the microvasculature and formation of tissue infarcts [54]. The concept of totally removing the blood and replacing it with a suitable acellular substitute solution is a novel approach, the feasibility of which we demonstrated in the 1990s [34,37,55]. In principle, this technique could provide a number of potential benefits over and above the obvious avoidance of the blood related complications.…”

“…Our working hypothesis was that acellular solutions can be designed to act as universal tissue preservation solutions during several hours of hypothermic whole-body washout involving cardiac arrest, with or without circulatory arrest. On this basis, we formulated and evaluated two new types of solutions designated 'Purge' and 'Maintenance' hypothermic blood substitutes (HBS) that fulfill separate requirements during the asanguineous procedure [1,34,55,62,63]. The principal solution (e.g.…”

“…Conceptually, this strategy would maximize the intrinsic qualities of the solutions that, by design as universal tissue preservation solutions, would inevitably be a hybrid of other hypothermic perfusates and storage media. The composition of the new hypothermic blood substitutes is listed in table 2, and the rationale for their formulation is described elsewhere [1,34,[64][65][66]. These solutions have been shown to protect the brain, heart and visceral organs during Taylor 3.5 h of cardiac arrest and global ischemia in an asanguineous canine model during controlled profound hypothermia at <10 °C [1,34,55] .…”