The isolated perfused rat liver: standardization of a time-honoured model

Abstract

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.

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