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The American Journal of Pathology logoLink to The American Journal of Pathology
. 1997 Jul;151(1):169–175.

Lymph vessel expansion and function in the development of hepatic fibrosis and cirrhosis.

B Vollmar 1, B Wolf 1, S Siegmund 1, A D Katsen 1, M D Menger 1
PMCID: PMC1857941  PMID: 9212743

Abstract

The process of lymph vessel expansion and function in the development of CCl4-induced hepatic fibrosis and cirrhosis was studied using intravital fluorescence microscopy of the rat liver. The unique aspect of our approach was the use of high molecular fluorescein-isothiocyanate-labeled dextran (MW, 150,000) as fluorescent marker, which allowed for simultaneous assessment of both 1) the macromolecular blood hepatocytic exchange from the sinusoidal microvasculature (extra-/intrasinusoidal gray level intensity at 1, 3, 5, and 10 minutes after intravenous injection) and 2) the hepatic lymph system. In animals exposed with CCl4 up to 4 weeks, macromolecular trans-sinusoidal exchange was found progressively delayed. This was strongly associated with lymph vessel expansion and function, as indicated by a continuous increase of lymph vessel density and area. Delay of macromolecular exchange and lymph vessel expansion was found not further enhanced at fibrotic and cirrhotic stages of 8- and 12-week CCl4-exposed livers. Linear regression analysis revealed a strong negative correlation between lymphatic network density development and macromolecular trans-sinusoidal exchange (r2 = 0.99; P < 0.01). Thus, our study provides for the first time direct evidence for the pivotal role of lymphatic function for macromolecular transport in case of deteriorated sinusoidal hepatocellular exchange capacity.

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Selected References

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  1. Aspestrand F., Schrumpf E., Jacobsen M., Hanssen L., Endresen K. Increased lymphatic flow from the liver in different intra- and extrahepatic diseases demonstrated by CT. J Comput Assist Tomogr. 1991 Jul-Aug;15(4):550–554. doi: 10.1097/00004728-199107000-00004. [DOI] [PubMed] [Google Scholar]
  2. DUMONT A. E., MULHOLLAND J. H. Flow rate and composition of thoracic-duct lymph in patients with cirrhosis. N Engl J Med. 1960 Sep 8;263:471–474. doi: 10.1056/NEJM196009082631001. [DOI] [PubMed] [Google Scholar]
  3. Hultström D., Svensjö E. Simultaneous fluorescence and electron microscopical detection of bradykinin induced macromolecular leakage. Bibl Anat. 1977;(15 Pt 1):466–468. [PubMed] [Google Scholar]
  4. Laine G. A., Hall J. T., Laine S. H., Granger J. Transsinusoidal fluid dynamics in canine liver during venous hypertension. Circ Res. 1979 Sep;45(3):317–323. doi: 10.1161/01.res.45.3.317. [DOI] [PubMed] [Google Scholar]
  5. Lautt W. W., Greenway C. V. Conceptual review of the hepatic vascular bed. Hepatology. 1987 Sep-Oct;7(5):952–963. doi: 10.1002/hep.1840070527. [DOI] [PubMed] [Google Scholar]
  6. Ludwig J., Linhart P., Baggenstoss A. H. Hepatic lymph drainage in cirrhosis and congestive heart failure. A postmortem lymphangiographic study. Arch Pathol. 1968 Nov;86(5):551–562. [PubMed] [Google Scholar]
  7. Martinez-Hernandez A., Martinez J. The role of capillarization in hepatic failure: studies in carbon tetrachloride-induced cirrhosis. Hepatology. 1991 Nov;14(5):864–874. doi: 10.1002/hep.1840140519. [DOI] [PubMed] [Google Scholar]
  8. Martinez-Hernandez A. The hepatic extracellular matrix. II. Electron immunohistochemical studies in rats with CCl4-induced cirrhosis. Lab Invest. 1985 Aug;53(2):166–186. [PubMed] [Google Scholar]
  9. Pries A. R. A versatile video image analysis system for microcirculatory research. Int J Microcirc Clin Exp. 1988 Nov;7(4):327–345. [PubMed] [Google Scholar]
  10. Proctor E., Chatamra K. High yield micronodular cirrhosis in the rat. Gastroenterology. 1982 Dec;83(6):1183–1190. [PubMed] [Google Scholar]
  11. Sadek A. M., Ismail A. M., Aboul Enein A., Hassanein E., Massoud O. G., El-Assi M. H. Percutaneous trans hepatic lymphography: evaluation in schistosomal hepatic fibrosis. Lymphology. 1976 Jun;9(2):47–52. [PubMed] [Google Scholar]
  12. Shimada Y. Observations on hepatic superficial lymph flow. Lymphology. 1979 Mar;12(1):11–13. [PubMed] [Google Scholar]
  13. Tsukamoto H., Matsuoka M., French S. W. Experimental models of hepatic fibrosis: a review. Semin Liver Dis. 1990 Feb;10(1):56–65. doi: 10.1055/s-2008-1040457. [DOI] [PubMed] [Google Scholar]
  14. Vollmar B., Glasz J., Leiderer R., Post S., Menger M. D. Hepatic microcirculatory perfusion failure is a determinant of liver dysfunction in warm ischemia-reperfusion. Am J Pathol. 1994 Dec;145(6):1421–1431. [PMC free article] [PubMed] [Google Scholar]
  15. Witte C. L., Witte M. H., Dumont A. E. Lymph imbalance in the genesis and perpetuation of the ascites syndrome in hepatic cirrhosis. Gastroenterology. 1980 May;78(5 Pt 1):1059–1068. [PubMed] [Google Scholar]
  16. Witte M. H., Dumont A. E., Cole W. R., Witte C. L., Kintner K. Lymph circulation in hepatic cirrhosis: effect of portacaval shunt. Ann Intern Med. 1969 Feb;70(2):303–310. doi: 10.7326/0003-4819-70-2-303. [DOI] [PubMed] [Google Scholar]

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