Isolated perfused liver model: the rat and guinea pig compared.
OBJECTIVE
Although the rat is the most commonly used species for the study of hepatic metabolism, the physiology of the guinea pig is closer to human physiology. We compared the model of isolated perfused guinea pig liver with the classic model of isolated perfused rat liver, especially with respect to amino acid metabolism.


METHODS
After validation of an anesthetic mixture of ketamine, diazepam, and xylazine for the guinea pig, isolated perfused livers were harvested for both species. Three groups of animals were compared for the study of liver metabolic fluxes: 6-wk-old male Sprague-Dawley rats (R; 230 +/- 10 g, n = 5), young male Hartley guinea pigs (YG; 223 +/- 8 g, n = 6) matched to rats by liver weight, and adult male Hartley guinea pigs (AG; 389 +/- 5 g, n = 6) matched to rats by age. Results (mean +/- standard error of the mean) were compared by analysis of variance and Newman-Keuls tests.


RESULTS
Both models displayed a satisfactory hepatic viability, but differences were noted, with higher portal flows (R: 3.1 +/- 0.3 versus YG: 4.5 +/- 0.3 and AG: 4.2 +/- 0.3 mL. min(-1). g(-1); P < 0.05, YG and AG versus R) and bile flows (R: 0.34 +/- 0.01 versus YG: 2.38 +/- 0.22 versus AG: 3.17 +/- 0.28 microL. min(-1). g(-1); P < 0.05, YG and AG versus R, and YG versus AG) and higher amino acid fluxes (P < 0.05) leading to greater nitrogen uptake (P < 0.05) in guinea pigs. We performed a second set of experiments to evaluate the influence of anesthesia and portal flow on this last parameter. In these experiments, rats were anesthetized with ketamine, diazepam, and xylazine and guinea pig livers were perfused at rat blood flow. Apart from a 50% anesthesia-related mortality for rats, bile flow and metabolic parameters were only slightly modified. However, some amino acid fluxes were statistically different (aspartate, serine, and histidine; P < 0.05), as confirmed by a higher transfer constant.


CONCLUSIONS
Our results indicate that the isolated perfused guinea pig liver is a suitable model for the study of hepatic metabolism.
Chaïb
Samira
S
Laboratoire de Biologie de la Nutrition EA 2498, Faculté de Pharmacie, Laboratoire de Biochimie A, Hôpital Hôtel-Dieu AP-HP, Paris, France.
Charrueau
Christine
C
Neveux
Nathalie
N
Coudray-Lucas
Colette
C
Cynober
Luc
L
De Bandt
Jean-Pascal
JP
D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D006168:Guinea Pigs; D008099:Liver / Q000378:metabolism*; D008102:Liver Circulation; D008297:Male; D023421:Models, Animal; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D013045:Species Specificity
D000596:Amino Acids