Machine perfusion

Machine perfusion (MP) is a technique used in organ transplantation as a means of preserving the organs which are to be transplanted. Machine perfusion (MP) is a technique used in organ transplantation as a means of preserving the organs which are to be transplanted. 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). An essential preliminary to the development of kidney storage and transplantation was the work of 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. These methods of surface cooling were improved by the introduction of techniques in which the kidney's vascular system was flushed out with cold fluid prior to storage. This had the effect of increasing the speed of cooling of the kidney and removed red cells from the vascular system. Kiser used this technique to achieve successful 7 hours in vitro storage of a dog kidney, when the kidney had been flushed at 5 °C with a mixture of dextran and diluted blood prior to storage. In 1960 Lapchinsky confirmed that similar storage periods were possible, when he reported 8 dogs surviving after their kidneys had been stored at 2-4 °C for 28 hours, followed by auto-transplantation and delayed contralateral nephrectomy. Although Lapchinsky gave no details in his paper, Humphries reported that these experiments had involved cooling the kidneys for 1 hour with cold blood, and then storage at 2-4 °C, followed by rewarming of the kidneys over 1 hour with warm blood at the time of reimplantation. The contralateral nephrectomies were delayed for 2 months. Humphries developed this storage technique by continuously perfusing the kidney throughout the period of storage. He used diluted plasma or serum as the perfusate and pointed out the necessity for low perfusate pressures to prevent kidney swelling, but admitted that the optimum values for such variables as perfusate temperature, Po2, and flow, remained unknown. His best results, at this time, were 2 dogs that survived after having their kidneys stored for 24 hours at 4-10 °C followed by auto-transplantation and delayed contralateral nephrectomy a few weeks later. Calne challenged the necessity of using continuous perfusion methods by demonstrating that successful 12-hour preservation could be achieved using much simpler techniques. Calne had one kidney supporting life even when the contralateral nephrectomy was performed at the same time as the reimplantation operation. Calne merely heparinised dog kidneys and then stored them in iced solution at 4 °C. Although 17-hour preservation was shown to be possible in one experiment when nephrectomy was delayed, no success was achieved with 24-hour storage.