Normothermic reperfusion
Organ perfusion at normal temperature can mimic normal function, but normothermic perfusion as a means of storage has not been possible for prolonged periods without seriously damaging the organ. Kootstra and his colleagues demonstrated that intermittent brief normothermic blood perfusion during cold storage improved preservation of both ice-stored and machine-perfused kidneys. The mechanisms of action are uncertain, but may relate to replenishing cellular energy stores and protecting the vasculature. The technique has not yet found clinical application.
Freezing and vitrification
Freezing is normally lethal to cells. Red cells, lymphocytes, spermatozoa, fertilized ova, embryos, and pancreatic islet cells can all be frozen and thawed satisfactorily in the presence of cryoprotectants. Simple tissues such as skin and cornea can also be preserved by freezing. Unfortunately freezing of organs, so attractive in concept in approaching true suspended animation and indefinite storage, has not proved feasible to date. The low surface area to volume ratio of organs compared to cells makes effective heat exchange a major problem. Cryoprotectants such as glycerol and dimethyl sulphoxide need to be present in high concentrations for adequate cryoprotection and this causes severe organ toxicity and vascular damage. Extracellular ice formation is innocuous when freezing cell suspensions, but can disrupt and severely damage the morphology of whole organs. The vascular system is especially vulnerable, and the attachment of vascular endothelial basement membrane is disrupted by freezing. Total vitrification of tissues is an alternative approach, but is also unsuccessful for whole organs. The tissue is first perfused with high concentrations of several cryoprotectants, so that on cooling neither intracellular nor extracellular freezing occurs. The solution vitrifies (i.e. solidifies into a glass state) at temperatures of approximately.
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