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

Clinical applications of hypothermia range from ex vivo storage of cells, tissues and organs for transplantation or cell-based therapies to in vivo protection of a patient during complex surgeries that might entail circulatory and/or cardiac arrest. The intent of this brief review is to outline the essential principles of hypothermia applied in the preservation of cells for a multitude of clinical purposes. The focus will be confined to our ability as interventionalists to control the environment of cells to optimize hypothermic preservation. More specifically, this review will summarize the design principles of hypothermic blood substitutes (HBS) defined as preservation solutions for protection of cells, tissues and organs during a hypothermic preservation interval. In contrast to the types of solutions that have been used historically as hemodiluents for clinical hypothermia, i.e. normal physiologically balanced salt solutions, our approach has been to design aqueous blood substitutes that embody many of the principles now identified as contributory and important for optimal ex vivo organ preservation. The working hypothesis that we have addressed using a variety of pre-clinical large animal models is 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, two new types of solutions, designated 'Purge' and 'Maintenance' HBS, have been formulated and evaluated to fulfill separate requirements during the asanguineous procedure. The evidence supporting this concept is reviewed in the context of imminent clinical trials to apply this novel technique for the preservation and resuscitation of trauma victims suffering hemorrhagic shock.