Machine perfusion
Machine perfusion
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Machine perfusion

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Machine perfusion

Machine perfusion (MP) is an artificial perfusion technique often used for organ preservation to help facilitate organ transplantation. MP works by continuously pumping a specialized solution through donor organs, mimicking the body's natural blood flow while actively controlling temperature, oxygen levels, chemical composition, and mechanical stress within the organ. By maintaining organ viability outside the body for extended periods, machine perfusion addresses critical challenges in organ transplantation, such as limited preservation times.

Machine perfusion has various forms and can be categorised according to the temperature of the perfusate: cold (4 °C) and warm (37 °C). Machine perfusion has been applied to renal transplantation, liver transplantation and lung transplantation. It is an alternative to static cold storage (SCS).

A record-long of human transplant organ preservation with machine perfusion of a liver for 3 days rather than usually <12 hours was reported in 2022. It could possibly be extended to 10 days and prevent substantial cell damage by low temperature preservation methods. Alternative approaches include novel cryoprotectant solvents.

There is a novel organ perfusion system under development that can restore, i.e. on the cellular level, multiple vital (pig) organs one hour after death (during which the body had a prolonged warm ischaemia), and a similar method/system for reviving (pig) brains hours after death. The system for cellular recovery could be used to preserve donor organs or for revival-treatments in medical emergencies.

An essential preliminary to the development of kidney storage and transplantation was the work of Alexis Carrel in developing methods for Vascular anastomosis. Carrel went on to describe the first kidney transplants, which were performed in dogs in 1902; Ullman independently described similar experiments in the same year. In these experiments kidneys were transplanted without there being any attempt at storage.

The crucial step in making in vitro storage of kidneys possible, was the demonstration by Fuhrman in 1943, of a reversible effect of hypothermia on the metabolic processes of isolated tissues. Prior to this, kidneys had been stored at normal body temperatures using blood or diluted blood perfusates, but no successful reimplantations had been made. Fuhrman showed that slices of rat kidney cortex and brain withstood cooling to 0.2 °C for one hour at which temperature their oxygen consumption was minimal. When the slices were rewarmed to 37 °C their oxygen consumption recovered to normal.

The beneficial effect of hypothermia on ischaemic intact kidneys was demonstrated by Owens in 1955 when he showed that, if dogs were cooled to 23-26 °C, and their thoracic aortas were occluded for 2 hours, their kidneys showed no apparent damage when the dogs were rewarmed. This protective effect of hypothermia on renal ischaemic damage was confirmed by Bogardus who showed a protective effect from surface cooling of dog kidneys whose renal pedicles were clamped in situ for 2 hours. Moyer demonstrated the applicability of these dog experiments to the human, by showing the same effect on dog and human kidney function from the same periods of hypothermic ischaemia.

It was not until 1958 that it was shown that intact dog kidneys would survive ischaemia even better if they were cooled to lower temperatures. Stueber showed that kidneys would survive in situ clamping of the renal pedicle for 6 hours if the kidneys were cooled to 0-5 °C by being placed in a cooling jacket, and Schloerb showed that a similar technique with cooling of heparinised dog kidneys to 2-4 °C gave protection for 8 hours but not 12 hours. Schloerb also attempted in vitro storage and auto-transplantation of cooled kidneys, and had one long term survivor after 4 hours kidney storage followed by reimplantation and immediate contralateral nephrectomy. He also had a near survivor, after 24-hour kidney storage and delayed contralateral nephrectomy, in a dog that developed a late arterial thrombosis in the kidney.

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