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.

Our results indicate that the oxygen concentration of the persufflation gas rather than the persufflation pressure is a determinant of successful tissue oxygenation during cold storage.

This study was undertaken in order to assess the role of purely circulation-related effects upon free-radical-mediated reperfusion injury in the liver by comparing the respective effects of the oxygen free-radical scavenger superoxide dismutase (SOD) and the vasodilative action of papaverine in an ischemia/reperfusion model of the liver. Livers from male Wistar rats were rinsed blood free via the portal vein and stored ischemically (60 min at 37 °C in Krebs-Henseleit solution and 60 min at 4 °C in Euro-Collins solution). Reperfusion was carried out at a constant flow of 30 ml/min for 45 min at 37 °C in a nonrecirculating manner. Warm ischemic damage was evident in untreated livers compared to control livers, submitted solely to cold ischemia for 2 h at 4°C, by increased vascular resistance upon reperfusion, enhanced enzyme leakage from the parenchyme (glutamate pyruvate transaminase, glutamate dehydrogenase) and from the endothelium (purine-nucleoside phosphorylase), reduced tissue content of ATP and enhanced lipid peroxidation. Preischemic treatment with SOD or papaverine (the latter also given during reperfusion) significantly reduced hepatic vascular resistance and parenchymal enzyme loss in a comparable manner. Both drugs resulted in a significant increase of hepatic tissue content of ATP at the end of reperfusion. SOD, but not papaverine, prevented the leakage of purine-nucleoside phosphorylase and significantly reduced the tissue levels of lipid peroxides. Since induced vasodilatation by papaverine mimicked the beneficial effects of SOD on hepatocellular viability after reperfusion, we conclude that toxic oxygen species exert a major impact on the vascular system and that the hepatocyte is significantly altered by circulatory disturbances during reperfusion, which can be reduced by SOD as well as papaverine.

No abstract

The use of a pneumoperitoneum with carbon dioxide significantly affects peritoneal tPA activity and thus may represent a stimulus for adhesion formation.

Reintroduction of oxygen to previously anoxic tissue may result in severe cell injury (oxygen paradox) and contribute to the socalled reperfusion damage of ischemic organs. Our study investigated the influence of simple gaseous oxygen supply during ischemia on nonparenchymal cell alterations upon reperfusion of the liver. Livers from male Wistar rats were isolated, rinsed blood-free and stored for 48 h at 4 "C in UW-preservation solution (group 1; n = 6). Gaseous oxygen was insufflated into a second group of livers (group 2; n = 6) during the storage period via the inferior caval vein at a pressure limited to 18 mmHg. To simulate the period of slow rewarming of the organ during surgical implantation in vivo, all livers were incubated at 25 "C in saline solution for 30 min prior to reperfusion. Reperfusion was carried out in vitro in a recirculating system with Krebs-Henseleit buffer. A control group was perfused immediately after harvest. The technique of aerobic storage (group 2) resulted in

No abstract

In the present study, levels of free oxygen radicals, generated in the very early period of reperfusion during human kidney transplantation, were assessed by determination of malondialdehyde (MDA) levels using a high-pressure liquid chromatography (HPLC) method. Renal blood samples were obtained during reperfusion by intraoperative cannulation of the renal vein. Simultaneously, systemic MDA levels were determined. Furthermore, local and systemic levels of interleukin 6 (IL-6), tumor necrosis factor (TNF) receptors, p55 and p75, and vitamin E were measured. In a second group of patients, 500 mg of ascorbic acid were given prior to reperfusion. Renal MDA levels in the control group were al-ways higher compared to systemic levels. IL-6 showed a marked increase shortly after reperfusion in the renal blood. In the scavenger group there was a diminution of these effects. TNF receptor levels and vitamin E remained largely unchanged. The results of this pilot study demonstrated clinically the moderate production of reactive oxygen species and the liberation of IL-6 shortly after reperfusion of human transplanted kidneys. Furthermore, the modulating effect of a radical scavenger on these effects was shown.