“…Small blebs with high electron density and IMP redistribution are observed at 8 h and these ceils are apparently more vulnerable to cold storage than hepatocytes. There are contradictory reports of the fate of the KulCffer cell, some report that it is activated [4,34], while others consider it to be injured [2,20]. Activation and injury may both occur.…”
To identify subtle changes which might lead to liver failure after liver transplantation, rat livers stored at 4 degrees C in University of Wisconsin solution for 8, 16, 24, and 32 h were examined by transmission electron microscopy, scanning electron microscopy, cellular matrix maceration and freeze fracture for ultrastructural analysis. Endothelial cells exhibited aggregation of intramembrane particles (IMPs) at 8 h and produced tiny blebs accompanied by marked development of pits. As deterioration advanced, endothelial cells exposed the perisinusoidal faces of hepatocytes directly to the lumen with destruction of sieve plates. They then degraded with loss of IMPs. Macrophages followed a similar deterioration process to endothelial cells. Membranes of hepatocytes did not demonstrate aggregations of IMPs for 32 h. Rough endoplasmic reticulum (rER) lost ribosomes and smooth ER (sER) increased in amount and dilated in an irregular form. Autophagosomes appeared in the cytoplasm, engulfed cytoplasmic matrix containing intracellular organelles and became autophagic vacuoles. At 32 h bile canaliculi were filled with detached vesicles. This may be one of the causes of preservation related bile duct complications after liver transplantation.
“…Small blebs with high electron density and IMP redistribution are observed at 8 h and these ceils are apparently more vulnerable to cold storage than hepatocytes. There are contradictory reports of the fate of the KulCffer cell, some report that it is activated [4,34], while others consider it to be injured [2,20]. Activation and injury may both occur.…”
To identify subtle changes which might lead to liver failure after liver transplantation, rat livers stored at 4 degrees C in University of Wisconsin solution for 8, 16, 24, and 32 h were examined by transmission electron microscopy, scanning electron microscopy, cellular matrix maceration and freeze fracture for ultrastructural analysis. Endothelial cells exhibited aggregation of intramembrane particles (IMPs) at 8 h and produced tiny blebs accompanied by marked development of pits. As deterioration advanced, endothelial cells exposed the perisinusoidal faces of hepatocytes directly to the lumen with destruction of sieve plates. They then degraded with loss of IMPs. Macrophages followed a similar deterioration process to endothelial cells. Membranes of hepatocytes did not demonstrate aggregations of IMPs for 32 h. Rough endoplasmic reticulum (rER) lost ribosomes and smooth ER (sER) increased in amount and dilated in an irregular form. Autophagosomes appeared in the cytoplasm, engulfed cytoplasmic matrix containing intracellular organelles and became autophagic vacuoles. At 32 h bile canaliculi were filled with detached vesicles. This may be one of the causes of preservation related bile duct complications after liver transplantation.
“…In a similar fashion as for the kidney, the metabolic benefits of HMP for the liver have been expounded since early studies in canine [82] and porcine [83] livers showed good graft preservation. Resuscitation of energy metabolism during oxygenated HMP has been shown in large animal studies [84].…”
Organ transplantation has developed over the past 50 years to reach the sophisticated and integrated clinical service of today through several advances in science. One of the most important of these has been the ability to apply organ preservation protocols to deliver donor organs of high quality, via a network of organ exchange to match the most suitable recipient patient to the best available organ, capable of rapid resumption of life-sustaining function in the recipient patient. This has only been possible by amassing a good understanding of the potential effects of hypoxic injury on donated organs, and how to prevent these by applying organ preservation. This review sets out the history of organ preservation, how applications of hypothermia have become central to the process, and what the current status is for the range of solid organs commonly transplanted. The science of organ preservation is constantly being updated with new knowledge and ideas, and the review also discusses what innovations are coming close to clinical reality to meet the growing demands for high quality organs in transplantation over the next few years.
“…With the first generation perfusion machines it became possible to preserve kidneys for more than 72 h 22 and subsequently liver machine preservation became feasible as well. 2 Following the discovery of Collins solution, especially the development of the University of Wisconsin preservation solution (UW) 3,14 made it possible to better preserve organs statically without machine perfusion and maintain organ viability for transplantation. The CS preservation technique made organ preservation and transplantation a standard clinical procedure due to its simplicity and low cost.…”
To improve preservation of donor livers, we have developed a portable hypothermic machine perfusion (HMP) system as an alternative for static cold storage. A prototype of the system was built and evaluated on functionality. Evaluation criteria included 24 h of adequate pressure controlled perfusion, sufficient oxygenation, a maintained 0-4 degrees C temperature and sterile conditions. Porcine livers were perfused with pump pressures that were set at 4 mmHg (continuous, portal vein) and 30/20 mmHg, at 60 BPM (pulsatile, hepatic artery). Control livers were preserved using the clinical golden standard: static cold storage. In the HMP group, pressure, flow and temperature were continuously monitored for 24 h. At time-points t = 0, 2, 4, 8, 12, and 24 h samples of University of Wisconsin machine preservation solution were taken for measurement of partial oxygen pressure (pO(2)) and lacto-dehydrogenase. Biopsies in every lobe were taken for histology and electron microscopy; samples of ice, preservation solution, liver surface, and bile were taken and cultured to determine sterility. Results showed that temperature was maintained at 0-4 degrees C; perfusion pressure was maintained at 4 mmHg and 30/20 mmHg for portal vein and hepatic artery, respectively. Flow was approximately 350 and 80 ml/min, respectively, but decreased in the portal vein, probably due to edema formation. Arterial pO(2) was kept at 100 kPa. Histology showed complete perfusion of the liver with no major damage to hepatocytes, bile ducts, and non-parenchymal cells compared to control livers. The machine perfusion system complied to the design criteria and will have to demonstrate the superiority of machine perfusion over cold storage in transplant experiments.
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