Surgery Today

, Volume 27, Issue 6, pp 518–526

Acute portal hypertension reflecting shear stress as a trigger of liver regeneration following partial hepatectomy

  • Yoshinobu Sato
  • Shuntaro Koyama
  • Kazuhiro Tsukada
  • Katsuyoshi Hatakeyama
Original Articles

Abstract

The concept of injury in liver regeneration after partial hepatectomy (PHx), and the reason hepatocytes that have not been directly injured regenerate, remain unclear. It is known that shear stress resulting from blood flow plays an important role in the mechanism of remodeling blood vessels, and portal pressure reflects shear stress. This study was conducted to determine whether acute portal hypertension (APH) can become a trigger of liver regeneration as shear stress following PHx in a rat model. Portal pressures became elevated immediately after 70% and 90% PHx, peaking on postoperative day (POD) 3, and thereafter decreasing in proportion to the diminution of liver regeneration. The portal pressures after 90% PHx were significantly higher than those after 70% PHx even on POD 7, while those of the portocaval (PC) shunt groups decreased following PC shunting both with and without 70% PHx. The liver/body weight (LW/BW) ratio also decreased in the PC shunt both with and even without 70% PHx. The gradient expressions of class I antigen on sinusoidal endothelial cells (SEC) were found only in the periportal area, which has the highest portal pressure in the healthy rat liver. However, after hepatectomy these expressions were detected from the periportal area to the central venous area. These results suggest that APH as shear stress following PHx may not only become a trigger of hepatocyte regeneration, but also of SEC regeneration, and that surplus APH induces liver dysfunction.

Key Words

liver regeneration partial hepatectomy portal pressure shear stress rats 

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References

  1. 1.
    Leffert HL, Koch KS (1980) Ionic events at the membrane initiate rat liver regeneration. Ann NY Acad Sci 888:201–215Google Scholar
  2. 2.
    Thoma R (1911) Über die Histomechanik des gefa Systems und die Pathogenese der Angiosklerose. Path Anat Physiol 204:1–74Google Scholar
  3. 3.
    Ando J, Tsuboi H, Korenaga R, Takada Y, Toyama SN, Miyasaka M, Kamiya A (1994) Shear stress inhibits adhesion of cultured mouse endothelial cells to lymphocytes by downregulating VCAM-1 expression. Am J Physiol 267:C679-C687PubMedGoogle Scholar
  4. 4.
    Hsieh HJ, Li NQ (1993) Pulsatile and steady flow induces c-fos expression in human endothelial cells. J Cell Physiol 154:143–151CrossRefPubMedGoogle Scholar
  5. 5.
    Ohno M, Lopez F, Gibbons GH, Cooke JP, Dzau VJ (1992) Shear stress-induced TGF-β 1 is mediated via a K+ channel (abstract). Circulation 86:I-87Google Scholar
  6. 6.
    Marsden PA, Heng HH, Scherer SW, Stewart RJ, Hall AV, Shi XM, Tsui LC, Schappert KT (1993) Structure and chromosomal localization of the human constitutive endothelial nitric oxide synthase gene. J Biol Chem 268:17478–17488PubMedGoogle Scholar
  7. 7.
    Higgins GM, Anderson RM (1931) Experimental pathology of the liver of the white rat following partial surgical removal. Arch Pathol 12:186–202Google Scholar
  8. 8.
    Weinbren K, Woodward E (1964) Delayed incorporation of P32 from orthophosphate into deoxyribonucleic acid of rat liver after subtotal hepatectomy. Brit J Exp Path 45:442–449PubMedGoogle Scholar
  9. 9.
    Bucher NLR, McGowan JA, patel U (1987) Hormonal regulation of liver growth. In: Dirksen ER, Prescott DM, Fox CF (eds) Cell reproduction. ICN/UCLA Symposium on Molecular Biology. Academic, New York, pp 661–670Google Scholar
  10. 10.
    Sato Y, Tsukada K, Matsumoto Y, Abo T (1993) Interferon-γ inhibits liver regeneration by stimulating major histocompatibility complex class II antigen expression by regenerating liver. Hepatology 18:340–346CrossRefPubMedGoogle Scholar
  11. 11.
    Gruppuso P, Mead J, Fausto N (1990) Transforming growth factor receptors in liver regeneration following partial hepatectomy in the rat. Cancer Res 50:1464–1469PubMedGoogle Scholar
  12. 12.
    Ohtake M, Sakaguchi T, Yoshida K, Muto T (1993) Hepatic branch vagotomy can suppress liver regeneration in partially hepatectomized rats. HPB Surg 6:277–286PubMedGoogle Scholar
  13. 13.
    Kamiya A, Togawa T (1980) Adaptive regulation of wall shear stress to flow change in the canine carotid artery. Am J Physiol 239:H14-H21PubMedGoogle Scholar
  14. 14.
    Langille LG, O'Donnell F (1986) Reductions in arterial diameter produced by chronic decrease in blood flow are endothelium-dependent. Science 231:405–407PubMedGoogle Scholar
  15. 15.
    Sato Y, Tsukada K, Yoshida K, Muto T (1992) FK506 suppresses class II antigen expression in regenerating liver following partial hepatectomy in the rat. Transplant Proc 24:1628–1630PubMedGoogle Scholar
  16. 16.
    Fraser R, Bowler LM, Day WA, Dobbs B, Johnson HD, Lee D (1980) High perfusion pressure damages the sieving ability of sinusoidal endothelium in rat livers. Br J Exp Pathol 61:222–228PubMedGoogle Scholar
  17. 17.
    Oda M, Nakamura M, Watanabe N, Ohya Y, Sekuzuka E, Tsukada N, Yonei Y (1983) Some dynamic aspects of the hepatic microcirculation-demonstration of sinusoidal endothelial fenestrae as a possible regulatory factor. In: Tsuchiya M, Wayland H, Oda M, Okazaki I (eds) Intravital observation of organ microcirculation. Excerpta Medica, Amsterdam, pp 105–138Google Scholar
  18. 18.
    Nakata K (1961) Direct measurement of blood pressures in minute vessels of the liver. Am J Physiol 199:1181–1188Google Scholar
  19. 19.
    Morello D, FitzGerald MJ, Babinet C, Fausto N (1990) c-myc, c-fos, and c-jun regulation in the regenerating livers of normal and H2K/c-myc transgenic mice. Mol Cell Biol 10:3185–3193PubMedGoogle Scholar
  20. 20.
    Fausto N, Mead JE, Gruppuso PA, Braun L (1990) TGF-β in liver development, regeneration, and carcinogenesis. Ann NY Acad Sci 593:231–242PubMedGoogle Scholar
  21. 21.
    Sonsoles H, Beatrice D, Ana MG, Maria JM D-G, Lisardo B (1995) Nitric oxide is released in regenerating liver after partial hepatectomy. Hepatology 21:776–786Google Scholar
  22. 22.
    Braquet P, Paubert BM, Bourgain RM, Bussolino F, Hosford D (1989) PAF/cytokine auto-generated feedback networks in microvascular immune injury: consequences in shock, ischemia and graft rejection. J Lipid Mediat 1:75–112PubMedGoogle Scholar
  23. 23.
    Mizoguchi Y, Ichikawa Y, Kioka K, Kobayashi K, Yamamoto S, Morisawa S (1990) Possible involvement of platelet-activating factor in the induction of liver cell injury. Osaka City Med J 36:121–128PubMedGoogle Scholar
  24. 24.
    Sato Y, Tsukada K, Iiai T, Ohmori K, Yoshida K, Muto T, Watanabe H, Abo T (1993) Activation of extrathymic T cells in the liver during liver regeneration following partial hepatectomy. Immunology 78:86–91PubMedGoogle Scholar
  25. 25.
    Sato Y, Inoue S, Nagao T, Yoshida K, Akiyama N, Muto T (1991) Cyclosporine suppresses class II antigen expression in regenerating liver of rats after partial hepatectomy. Nippon Shokaki Geka Gakkai Zasshi (Jpn J Gastroenterol Surg) 24:172Google Scholar
  26. 26.
    Sato Y, Tsukada K, Koyama S, Hatakeyama K. Acute portal hypertension and activation of sinusoidal endothelial cells: Hypothesis of mechanism of hepatic necrosis following hepatectomy. Res Surg (in press)Google Scholar
  27. 27.
    Grisham JW (1994) Migration of hepatocytes along hepatic plates and stem cell-fed hepatocyte lineages. Am J Path 144:849–854PubMedGoogle Scholar
  28. 28.
    Zajicek G, Oren R, Weinreb (1985) The streaming liver. Liver 5:293–300PubMedGoogle Scholar
  29. 29.
    Arber N, Zajicek G, Ariel I (1988) The streaming liver II. Hepatocyte life history. Liver 8:80–87PubMedGoogle Scholar
  30. 30.
    Kennedy S, Rettinger S, Flye MW, Ponder KP (1995) Experiments in transgenic mice show that hepatocytes are the source for postnatal liver growth and do not stream. Hepatology 22:160–168CrossRefPubMedGoogle Scholar
  31. 31.
    Sandgren E, Palmiter R, Heckel J, Daugherty C, Brinster R, Degen J (1991) Complete hepatic regeneration after somatic deletion of an albumin-plasminogen activator transgene. Cell 66:245–256CrossRefPubMedGoogle Scholar
  32. 32.
    Schmiedeberg P, Biempica L, Czaja MJ (1993) Timing of protooncogene expression varies in toxin-induced liver regeneration. J Cell Physiol 154:294–300CrossRefPubMedGoogle Scholar
  33. 33.
    Fausto N (1990) Hepatic regeneration. In: Zakim D, Boyer TD (eds) Hepatology: a textbook of liver disease. Saunders, Philadelphia, pp 49–61Google Scholar

Copyright information

© Springer-Verlag 1997

Authors and Affiliations

  • Yoshinobu Sato
    • 1
  • Shuntaro Koyama
    • 1
  • Kazuhiro Tsukada
    • 1
  • Katsuyoshi Hatakeyama
    • 1
  1. 1.First Department of SurgeryNiigata University School of MedicineNiigataJapan

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