Research in Experimental Medicine

, Volume 186, Issue 6, pp 397–405 | Cite as

Structural and functional integrity of rat liver perfused in backward and forward directions

  • J. Schölmerich
  • S. Kitamura
  • K. Miyai
Original Papers


The purpose of this study was to assess if reversal of the direction of isolated rat liver perfusion would cause significant alterations in hepatic functions and structure.

Five isolated rat livers were perfused forward and another five backward with oxygenated Ringer's solution for up to 90 min (hydrostatic pressure: ≤ 13 cm H2O; flow rate: forward 3.88 ± 0.34 ml/min per gram and backward 3.76 ± 0.34 ml/min per gram). At the end of the experiment, livers were perfusion-fixed for morphological examination. The following results were obtained: No significant differences were noted between the forward and backward perfusions with respect to oxygen uptake, mean bile flow (forward 0.57 ± 0.12; backward 0.60 ± 0.14 ml/min per gram), average bile acid excretion (forward 2.39 ± 1.11; backward 2.83 ± 0.94 nmol/min per gram), hydroxylation pattern of bile acids, urea synthesis, release of lactic dehydrogenase, glucose secretion, and redox ratios. Light and electron microscopy, including morphometry of parenchymal and sinusoidal areas, revealed that the backward perfusion caused a greater degree of sinusoidal distension, but no other noteworthy differences. Hepatic ultrastructure was well preserved. We conclude that reversing the direction of perfusion does not alter structure and major hepatic functions significantly.

Key words

Isolated perfused rat liver Backward perfusion Hepatic functions Hepatic morphology 


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  1. 1.
    Andersen B, Nath A, Jungermann K (1982) Heterogeneous distribution of phosphoenolpyruvate carboxykinase in rat liver parenchyma, isolated, and cultured hepatocytes. Eur J Cell Biol 28:47–53PubMedGoogle Scholar
  2. 2.
    Arnold M, Rutter WJ (1963) Liver amylase. III. Synthesis by the perfused liver and secretion into the perfusion medium. J Biol Chem 238:2760–2765PubMedGoogle Scholar
  3. 3.
    Bengtsson BG, Kiessling K-H, Smith-Kielland A, Mørland J (1981) Partial separation and biochemical characteristics of periportal and perivenous hepatocytes from rat liver. Eur J Biochem 118:591–597PubMedGoogle Scholar
  4. 4.
    Bristow DA, Kerly M (1964) Transamination in perfused rat liver. J Physiol (Lond) 170:318–327Google Scholar
  5. 5.
    Brunengraber H, Boutry M, Daikuhara Y, Kopelovich L, Lowenstein JM (1975) Use of the perfused liver for the study of lipogenesis. Methods Enzymol 35:597–607PubMedGoogle Scholar
  6. 6.
    Chen EH, Gumucio JJ, Ho NH, Gumucio DL (1984) Hepatocytes of Zones 1 and 3 conjugate sulfobromophthalein with glutathione. Hepatology 4:467–476PubMedGoogle Scholar
  7. 7.
    Forker El, Luxon BA (1982) Hepatic transport kinetics: Effect of anatomic and metabolic heterogeneity on estimates of the average transfer coefficients. Am J Physiol 243:G532-G540PubMedGoogle Scholar
  8. 8.
    Fröhlich J, Schölmerich J, Hoppe-Seyler G, Maier KP, Talke H, Schollmeyer P, Gerok W (1974) The effect of acute uraemia on gluconeogenesis in isolated perfused rat livers. Eur J Clin Invest 4:453–458PubMedGoogle Scholar
  9. 9.
    Groothuis GMM, Hardonk MJ, Keulemans KPT, Nieuwenhuis P, Meijer DKF (1982) Autoradiographic and kinetic demonstration of acinar heterogeneity for taurocholate transport. Am J Physiol 243:G455-G462PubMedGoogle Scholar
  10. 10.
    Gumucio JJ, Miller DL (1982) Zonal hepatic function: Solute-hepatocyte interactions within the liver acinus. In: Popper H, Schaffner F (eds) Progress in liver diseases, vol 7. Grune & Stratton, New York, pp 17–30Google Scholar
  11. 11.
    Gumucio JJ, Miller DL (1981) Functional implications of liver cell heterogeneity. Gastroenterology 80:393–403PubMedGoogle Scholar
  12. 12.
    Gumucio JJ, Balabaud C, Miller DL, DeMason LJ, Appelman HD, Stoeker TJ, Franzblau DR (1978) Bile secretion and liver cell heterogeneity in the rat. J Lab Clin Med 91:350–362PubMedGoogle Scholar
  13. 13.
    Häussinger D, Gerok W (1985) Functional hepatocyte heterogeneity: The intercellular glutamate cycle, its regulation and physiologic significance. J Hepatol 1:1–12Google Scholar
  14. 14.
    Häussinger D, Gerok W, Sies H (1982) Inhibition of pyruvate dehydrogenase during the metabolism of glutamine and proline in hemoglobin-free perfused rat liver. Eur J Biochem 126:69–76PubMedGoogle Scholar
  15. 15.
    Hardison WGM, Wood CA (1978) Importance of bicarbonate in bile salt independent fraction of bile flow. Am J Physiol 235:E158-E164PubMedGoogle Scholar
  16. 16.
    Hechter O, Solomon MM, Caspi E (1953) Corticosteroid metabolism in liver: Studies on perfused rat livers. Endocrinology 53:202–215PubMedGoogle Scholar
  17. 17.
    Hems R, Ross BD, Berry MN, Krebs HA (1966) Gluconeogenesis in the perfused rat liver. Biochem J 101:284–292PubMedGoogle Scholar
  18. 18.
    Herz R, Paumgartner G, Preisig R (1975) Inhibition of bile formation by high doses of taurocholate in the perfused rat liver. Scand J Gastroenterol 11:741–746Google Scholar
  19. 19.
    Jungermann K, Katz N (1982) Functional hepatocellular heterogeneity. Hepatology 2:385–395PubMedGoogle Scholar
  20. 20.
    Mayes PA, Felts JM (1967) Lack of uptake and metabolism of the triglyceride of serum lipoproteins of density less than 1.006 by the perfused rat liver. Biochem J 105:18C-20CPubMedGoogle Scholar
  21. 21.
    Miller DL, Zanolli CS, Grumucio JJ (1979) Quantitative morphology of the sinusoids of the hepatic acinus. Gastroenterology 76:965–969PubMedGoogle Scholar
  22. 22.
    Maughan RJ (1982) A simple, rapid method for the determination of glucose, lactate, pyruvate, alanine, β-hydroxybutyrate and acetoacetate on a single 20-µl blood sample. Clin Chim Acta 122:231–240PubMedGoogle Scholar
  23. 23.
    Roda A, Kricka LJ, DeLuca M, Hofmann AF (1982) Bioluminescence measurement of primary bile acids using immobilized 7α-hydroxysteroid dehydrogenase: Application to serum bile acids. J Lipid Res 23:1354–1361PubMedGoogle Scholar
  24. 24.
    Ross BD (1972) Perfusion techniques in biochemistry: A laboratory manual. Clarendon Press, Oxford, pp 133–220Google Scholar
  25. 25.
    Schmucker DL, Curtis JC (1971) A correlated study of the fine structure and physiology of the perfused rat liver. Lab Invest 30:210–212Google Scholar
  26. 26.
    Schölmerich J, Hinkley JE, Macdonald IA, Hofmann AF, DeLuca M (1983) A bioluminescent assay for 12-α-hydroxy bile acids using immobilized enzymes. Anal Biochem 133:244–250PubMedGoogle Scholar
  27. 27.
    Schölmerich J, Henegouwen GP, Hofmann AF, DeLuca M (1984) A bioluminescence assay for total bile acids in serum using immobilized enzymes. Clin Chim Acta 137:21–32PubMedGoogle Scholar
  28. 28.
    Schölmerich J, Kitamura S, Miyai D (1983) Changes of the pattern of biliary bile acids during isolated rat liver perfusion. Biochim Biophys Res Commun 115:518–524Google Scholar
  29. 29.
    Schriefers H, Korus W (1960) Über die Kinetik des Stoffwechsels von Cortison, Prednison und 9-Fluor-Hydrocortison bei der Rattenleberperfusion. Hoppe-Seyler's Z Physiol Chem 318:238–249Google Scholar
  30. 30.
    Sies H (1978) The use of perfusion of liver and other organs for the study of microsomal electron-transport and cytochrome P-450 systems. Methods Enzymol 52:48–59PubMedGoogle Scholar
  31. 31.
    Stacey NH, Klaassen CD (1981) Uptake of galactose, ouabain, and taurocholate into centrilobular and periportal enriched hepatocyte subpopulations. J Pharmacol Exp Ther 216:634–639PubMedGoogle Scholar
  32. 32.
    Sugano T, Suda K, Shimada M, Oshino N (1978) Biochemical and ultrastructural evaluation of isolated rat liver systems perfused with a hemoglobin-free medium. J Biochem 83:995–1007PubMedGoogle Scholar
  33. 33.
    Thomas VH, Ganz F-J, Büschemann E (1968) Zur Biogenese von Homovanilloyl-glycin bei der Rattenleberperfusion. Hoppe-Seyler's Z Physiol Chem 349:1686–1690PubMedGoogle Scholar
  34. 34.
    Trowell OA (1942) Urea formation in the isolated perfused liver of the rat. J Physiol (Lond) 100:432–458Google Scholar
  35. 35.
    Van Dyke RW, Stephens JE, Scharschmidt BF (1982) Effects of ion substitution on bile acid-dependent and -independent bile formation by rat liver. J Clin Invest 505–517Google Scholar

Copyright information

© Springer-Verlag 1986

Authors and Affiliations

  • J. Schölmerich
    • 1
    • 2
  • S. Kitamura
    • 1
    • 2
  • K. Miyai
    • 1
    • 2
  1. 1.University of CaliforniaSan DiegoUSA
  2. 2.School of MedicineLa JollaUSA

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