SummaryFor many years, the isolated perfused rat liver (IPRL) model has been used to investigate the physiology and pathophysiology of the rat liver. This in vitro model provides the opportunity to assess cellular injury and liver function in an isolated setting. This review offers an update of recent developments regarding the IPRL set-up as well as the viability parameters that are used, with regards to liver preservation and ischaemia and reperfusion mechanisms.A review of the literature was performed into studies regarding liver preservation or liver ischaemia and reperfusion. An overview of the literature is given with particular emphasis on perfusate type and volume, reperfusion pressure, flow, temperature, duration of perfusion, oxygenation and on applicable viability parameters (liver damage and function).The choice of IPRL set-up depends on the question examined and on the parameters of interest. A standard technique is cannulation of the portal vein, bile duct and caval vein with pressure-controlled perfusion at 20 cm H 2 O (15 mmHg) to reach a perfusion flow of approximately 3 mL/min/g liver weight. The preferred perfusion solution is Krebs-Henseleit buffer, without albumin. The usual volume is 150-300 cm 3 , oxygenated to a pO 2 of more than 500 mmHg. The temperature of the perfusate is maintained at 371C. Standardized markers should be used to allow comparison with other experiments.Keywords Isolated perfused rat liver (IPRL); liver preservation; parameters; liver function; liver damage For many years, the isolated perfused rat liver (IPRL) model has been used to investigate the physiology and pathophysiology of the rat liver. This in vitro model provides the opportunity to assess cellular injury and liver function in an isolated setting.The IPRL model was first reported by Claude Bernard in 1855 (Gores et al. 1986).In the review about the IPRL written by Gores et al. in 1986, the authors stated that the model remained a valuable reperfusion model, although other methods such as the assessment of liver slices, cell cultures, cell suspensions and isolated organelles had emerged. To date, the IPRL provides valuable data in studies regarding liver physiology using new techniques in the field of molecular biology and genetics.In the field of liver preservation, the IPRL model has been used for, among others, assessment of ischaemia-reperfusion injury, metabolism of perfusate compounds, metabolism of ammonium and amino acids (Haussinger 1987), endothelial function using hyaluronic acid uptake (Reinders et al. 1996), oxygen consumption (Dahn et al.

Liver grafts are frequently discarded due to steatosis. Steatotic livers can be classified as suboptimal and deteriorate rapidly during hypothermic static preservation, often resulting in graft nonfunction. Hypothermic machine perfusion (MP) has been introduced for preservation of donor livers instead of cold storage (CS), resulting in superior preservation outcomes. The aim of this study was to compare CS and MP for preservation of the steatotic donor rat liver. Liver steatosis was induced in male Wistar rats by a choline-methionine-deficient diet. After 24 hours hypothermic CS using the University of Wisconsin solution (UW) or MP using UW-Gluconate (UW-G), liver damage (liver enzymes, perfusate flow, and hyaluronic acid clearance) and liver function (bile production, ammonia clearance, urea production, oxygen consumption, adenosine triphosphate [ATP] levels) were assessed in an isolated perfused rat liver model. Furthermore, liver biopsies were visualized by hematoxylin and eosin staining. Animals developed 30 to 60% steatosis. Livers preserved by CS sustained significantly more damage as compared to MP. Bile production, ammonia clearance, urea production, oxygen consumption, and ATP levels were significantly higher after MP as compared to CS. These results were confirmed by histology. In conclusion, MP improves preservation results of the steatotic rat liver, as compared to CS. Liver Transpl 13: 497-504, 2007.

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This study in a clinically relevant large animal model showed that a new preservation solution, POLYSOL, resulted in improved preservation quality of kidney grafts compared to the UW solution.

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Chronic shortage of donor organs has led to acceptance of steatotic livers as grafts, although there is a higher risk of primary graft dysfunction. We herein report the beneficial impact of Polysol, a newly developed preservation solution, on cold storage of steatotic rat livers. Dietary hepatic steatosis was induced in Wistar rats by 2-day fasting and subsequent 3-day re-feeding with a fat-free, carbohydrate-rich diet. Fatty livers were retrieved, flushed and then stored at 4°C for 24 hours with either HTK or Polysol. Functional integrity of the grafts was evaluated by isolated reperfusion with oxygenated Krebs-Henseleit buffer at 37°C for 45 minutes in both groups. Polysol preservation resulted in significant reductions of not only parenchymal (AST (IU/L); 6728Ϯ824 in HTK vs. 3107Ϯ718 in Polysol; P Ͻ 0.001) but also mitochondrial (GLDH (IU/L); 3189Ϯ773 vs. 1282Ϯ365; P Ͻ 0.01) enzyme release throughout reperfusion. Moreover, PVP (16.9Ϯ2.7 vs. 7.8Ϯ1.5 mmHg; P Ͻ 0.05), hepatic O 2 consumption (0.291Ϯ0.047 vs. 1.056Ϯ0.053 mol/g liver/min; P Ͻ 0.001), tissue ATP content (0.695Ϯ0.086 vs. 1.340Ϯ0.157 mol/g dry-liver; P Ͻ 0.005), bile production (0.79Ϯ0.11 vs. 4.08Ϯ0.66 L/g liver/45-min; P Ͻ 0.001), malondialdehyde into the perfusate (1.922Ϯ0.198 vs. 0.573Ϯ0.094 nmol/L; P Ͻ 0.0001) and wet/dry-weight ratio of the liver tissues (5.20Ϯ0.31 vs. 3.85Ϯ0.15; P Ͻ 0.005) were all better preserved by Polysol. In line with these benefits, electron microscopy revealed that Polysol preservation substantially suppressed deleterious mitochondrial alterations in steatotic livers. In conclusion, cold storage using Polysol resulted in significantly better integrity and function of steatotic livers. Polysol, therefore, may be a new alternative especially for "marginal" organs. Liver Transpl 13:114-121, 2007.

AIM:To evaluate the potential of Polysol, a newly developed preservation solution, in cold storage of small bowel grafts, compared with the current standards, University of Wisconsin solution (UW), Celsior and histidine-tryptophan-ketoglutarate solution (HTK). METHODS:Male Wistar rats were used as donors. Small bowels were retrieved, flushed and then stored in the respective 4 solutions for 18 h at 4℃. Functional integrity of the grafts was evaluated by isolated reperfusion with oxygenated Krebs-Henseleit buffer at 37℃ for 30 min in all 4 groups. RESULTS:Polysol preservation exhibited the highest tissue ATP concentration and the lowest release of LDH. Malondialdehyde, an index for tissue lipid peroxidation, w a s a l s o t h e l o w e s t i n Po l y s o l . T i s s u e o x y g e n consumption was significantly higher in Polysol than in the others. Of interest, UW-storage promoted 10-fold higher apoptosis than in the others. Moreover, electron microscopy revealed that the mucosal villi/micro-villi formation and the cell organelles, including mitochondria, were both significantly better preserved in Polysol, while deleterious alterations were apparent in the others, most notably in UW. Although Celsior and HTK exhibited the better trend of results than UW in some parameters, but could not reach the over-all superiority to UW. CONCLUSION:Cold storage using Polysol resulted in significantly better integrity and function of small bowel grafts than UW. Hence, Polysol may be a novel alternative for the small bowel preservation.