GV - SOLAS | Liver

38th Scientific Meeting (GV - SOLAS) Society for Laboratory Animal Science
Seminar on Isolated Perfused Organs (Essen, 2000)

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Liver

The isolated haemoperfused porcine liver - Effects of Polidocanol and Diclofenac
J. Pfeffer, P. Wevers, K. Leiterer, S. Nagel, C. Große-Siestrup et al.
Institute of Transfusion Medicine and Immunhaematology and Animal Experimental Facilities of Charite´, Campus Virchow Klinikum, Humboldt University, Berlin, Germany

Introduction
In the last years perfusion of isolated organs of large animals have been significantly improved (M. Schön, Transplantation, Vol. 56, 1993). This enables us to use livers from slaughter-house animals for testing acute toxicity and metabolic effects of drugs. The unintended systemic effect of Polidocanol, a drug for sclerosing veins, was subject of this study utilizing a liver perfusion system. Furthermore the metabolic effects of Diclofenac, a nonsteroidal antiphlogistic drug were studied.

Material and methods
A new perfusion setup (oxygenation and decarboxylation via 3 parallel F7 modules by the Fa. Fresenius) was used on 18 livers (1,5 - 2,5 kg weight) modifying the technique of H.v.Baeyer (Biomed. Technik, Bd. 42, p. 61, 1997). Three groups were investigated: Control (n = 6), Polidocanol (n = 6), Diclofenac (n = 6). Organs were canulated (A. hepatica, V. cava, Duct. Choledochus) and flushed with cold conservation solution (Euro-Collins) for up to four hours before reperfusion. During the experiment haemodynamic (art., portal vein pressure and blood flow) and bloodchemical parameters (AST, ALT, lactate, bicarbonate and pH) were measured every 15 minutes to monitore liver function.

Results

Parameter		AST (U/I)			ALT (U/I)			Art. pressure (mmHg)
Time (min)	0	15	30	0	15	30	0	15	30
Control	580,8	973,1	1504,1	55,8	61,3	82,8	64,1	71,3	68,5
Polidocanol 0,008%	579	1228,5	1778	56	101,2	134	64	61,3	58,7

Parameter	Bicarbonate			pH			Lactat (mg/dl)
Time (min)	0	15	30	0	15	30	0	15	30
Control	19	20,25	19,18	7,42	7,38	7,38	65,15	61,7	45,4
Diclofenac 0,033%	18,95	18,53	17,9	7,4	7,26	7,04	67,3	85	89,2

Discussion
At given concentrations the acute toxicity of Polidocanol and the metabolic influence of Diclofenac could clearly be demonstrated. As Diclofenac uncouples the oxydative phosphorylation in the CYP450 - System, bicarbonate and pH declined with subsequent lactate acidosis.
In this study we could show that artificial liver perfusion can actually deal with most of the parameters of interest in toxicity assessment. Further standardization and improvement of this technique can once become a powerful tool in replacing living animal testing.

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August 6, 2000