CHANGE OF ZONAL BILE-ACID PROCESSING AFTER PARTIAL-HEPATECTOMY IN THERAT

The aim of this study was to analyze whether partial hepatectomy alter s functional liver heterogeneity with respect to bile acid processing. One, 5 and 21 days after liver resection (approximate to 80% of liver mass) in male Sprague-Dawley rats (300-400 g), isolated livers mere p erfused in either the antegrade or the retrograde direction, respectiv ely, with 32 nmol cholate/min per g liver. Uptake, metabolism and bili ary secretion kinetics were determined by bolus injection of C-14-chol ate. Uptake and biliary recovery (within 30 min) of cholate were >90% in all groups, One day postresection, liver mass had already doubled a nd it regenerated to over 80% 5 days after resection, Serum bile acid concentration increased rapidly, peaking 6 h after resection (176.7+/- 28.5 mu mol/l) (mean+/-SEM. Twenty-one days after resection it fell to control values (23.2+/-3.8 mu mol/l). T-25 (T-50), the time (min) nec essary to excrete 25% (50) of the bile acid load into bile, was striki ngly different between periportal and pericentral cells of controls (1 .8 vs 5.7 and 3.4 vs 8.1). Five days after resection this difference b ecame smaller (1.4 vs 2.9 and 2.8 vs 5.5) due to accelerated biliary c holate secretion in pericentral cells. Pericentral cells of controls m etabolized cholate more extensively to taurocholate (approximate to 83 %) and glycocholate (approximate to 13%) than periportal cells of cont rols (65%, 10%), leading to a 5-fold higher proportion of unmetabolize d cholate in peri; portal than pericentral cells (25% vs 5%). Five day s after resection the percentage of taurocholate decreased significant ly at the expense of an increased formation of glycocholate. Twenty-on e days after resection, bile acid composition came to resemble that of controls, In conclusion, the results demonstrate a reduction of metab olic zonation with regard to bile acid processing after liver resectio n. Despite accelerated biliary bile acid secretion in pericentral cell s of the regenerating liver, overall metabolism was not impaired as co mpared to controls. This is comparable to weaning rats where functiona l liver heterogeneity has not yet developed,