HISTORICAL REVIEW

Attempts to preserve human tissues and organs from putrefaction and decay after death began in antiquity with the embalming and mummifying techniques which were developed to a fine art by the Egyptian dynasties. In the 1930s the classical experiments of Carrel and Lindbergh applied perfusion techniques to preservation of organs for transplantation. They established ground rules for organ preservation by continuous ex-vivo perfusion—expert technology, perfect asepsis, and controlled biological conditions.

The Spanish Civil War marked the advent of blood banks and clinical application of tissue storage techniques. Cold storage was used to diminish metabolic demand. Fortunately blood, the first widely preserved and transplanted biological substance, lent itself well to extended storage. Refrigerated storage was possible for 3 weeks.

The discovery of cryoprotectants by Polge and coworkers in 1949 ushered in a major extension of preservation times for a variety of simple cells and tissues. Blood cells and gametes (even embryos) could be stored after freezing. Weeks or months later, they could be thawed and successfully reimplanted as autografts or allografts. Such freezing was only successful for isolated cells or undifferentiated multicellular embryos: complex and heterogeneous organs were highly sensitive to freezing damage. The biophysical problems of freezing large organs were subsequently defined by Pegg and other workers. To date no consistent success has been obtained with the use of freezing to preserve organs such as kidneys, liver, or hearts. Concepts of frozen humans waiting revival at an appropriate future time on another planet or in an after-life remain in the realms of science fiction.

Hypothermic organ preservation, stopping short of freezing, has given more promising results for whole organs. Most early work centred on the kidney. Simple cooling and ice storage gave reliable protection for several hours only. In the 1960s Pegg and Calne showed that preservation could be improved by a cold intravascular flush. Initially the blood within the organ was replaced with fresh blood, plasma, or extracellular-like flushing solutions containing colloid. In 1969 Collins demonstrated the clear superiority of an ‘intracellular’ electrolyte flushing solution, high in potassium, magnesium, and phosphate, low in sodium and chloride, and without colloid. Kidney storage for 24 h became clinically practical, provided that the organ did not suffer too much damage due to periods of warm ischaemia prior to cooling. In the early 1970s Belzer et al. extended Carrel's work on recirculating machine perfusion. Machine storage extended the time during which kidneys could be reliably preserved from one day to 3 days. However, simple hypothermic storage (after flushing) and continuous machine perfusion gave equivalent results for 24-h preservation—particularly if warm ischaemia was avoided. It also became clear that flushing solutions did not need to mimic intracellular composition to be effective: other solutions, even simpler in composition, based on citrate and on sucrose were shown to be as effective as Collins' solution. Clinical kidney preservation and transport could rely mainly on simple hypothermic storage after preliminary flushing with these solutions compact cold perfusion machines using modifications of plasma were also available for more extended storage times. Belzer et al. gave a further major stimulus to preservation research in 1987, demonstrating that a complex multicomponent solution (University of Wisconsin (UW) solution) gave significantly enhanced preservation of several organs (particularly pancreas and liver). With a new colloid—hydroxyethyl starch, the UW solution was suitable for both simple flushing and recirculatory machine perfusion. Current research in many centres is evaluating the efficacy of the numerous components of UW solution, and attempting to improve it further. Modifications of UW solution have been successful in extending the time of preservation of pancreas, liver, kidney, and heart.

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Objectives
The problems
Partial solution
Cold perfusion
Phases preservation
Individual organs
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