Logo of amjpatholAmerican Journal of Pathology For AuthorsAmerican Journal of Pathology SubscribeAmerican Journal of Pathology SearchAmerican Journal of Pathology Current IssueAmerican Journal of Pathology About the JournalAmerican Journal of Pathology
Am J Pathol. 1994 Dec; 145(6): 1421–1431.
PMCID: PMC1887483

Hepatic microcirculatory perfusion failure is a determinant of liver dysfunction in warm ischemia-reperfusion.


Hepatic ischemia-reperfusion (I/R) is characterized by circulatory and metabolic derangements, liver dysfunction, and tissue damage. However, little is known about the causative role of I/R-induced microcirculatory disturbance on the manifestation of postischemic reperfusion injury. Therefore, the intention of the study was to assess changes of hepatic microvascular perfusion (intravital fluorescence microscopy) as related to hepatic morphology (light/electron microscopy), hepatocellular integrity (serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities), and excretory function (bile flow). Sprague-Dawley rats were subjected to 20 minutes (group B, n = 9) and 60 minutes (group C, n = 9) of left hepatic lobar ischemia followed by 60 minutes of reperfusion. Sham-operated animals without ischemia served as controls (group A, n = 10). Lobar ischemia for 20 minutes followed by reperfusion resulted in a significant reduction of sinusoidal perfusion rate (93.9 +/- 1.4%; P < 0.05) and a decrease in erythrocyte flux (90.0 +/- 5.6%) when compared with controls (99.4 +/- 0.2 and 97.9 +/- 2.7%). This was accompanied by a significant increase of serum AST and ALT activities (P < 0.05) and a reduction of bile flow (P < 0.05). Prolongation of lobar ischemia (group C, 60 minutes) aggravated postischemic reperfusion injury (sinusoidal perfusion rate: 87.4 +/- 2.9%; erythrocyte flux: 62.1 +/- 8.4%) and was paralleled by severed hepatocellular damage. Electron microscopy of postischemic tissue demonstrated alteration of nonparenchymal cells (swelling of sinusoidal lining cells and widening of Disse's space) and substantial parenchymal cell damage (swelling of mitochondria, disarrangement of rough endoplasmatic reticulum, vacuolization, complete cytoplasmic degeneration). Initial postischemic increase in serum AST and ALT activities and reduction of bile flow directly correlated with the extent of microcirculatory failure (P < 0.01), ie, impairment of sinusoidal perfusion and decrease of erythrocyte flux, indicating the decisive role of microvascular perfusion failure for the manifestation of hepatic tissue damage and liver dysfunction.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (3.4M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Pachter HL, Spencer FC, Hofstetter SR, Coppa GF. Experience with the finger fracture technique to achieve intra-hepatic hemostasis in 75 patients with severe injuries of the liver. Ann Surg. 1983 Jun;197(6):771–778. [PMC free article] [PubMed]
  • Delva E, Camus Y, Nordlinger B, Hannoun L, Parc R, Deriaz H, Lienhart A, Huguet C. Vascular occlusions for liver resections. Operative management and tolerance to hepatic ischemia: 142 cases. Ann Surg. 1989 Feb;209(2):211–218. [PMC free article] [PubMed]
  • Huguet C, Gavelli A, Chieco PA, Bona S, Harb J, Joseph JM, Jobard J, Gramaglia M, Lasserre M. Liver ischemia for hepatic resection: where is the limit? Surgery. 1992 Mar;111(3):251–259. [PubMed]
  • Hasselgren PO. Prevention and treatment of ischemia of the liver. Surg Gynecol Obstet. 1987 Feb;164(2):187–196. [PubMed]
  • Chaudry IH. Cellular mechanisms in shock and ischemia and their correction. Am J Physiol. 1983 Aug;245(2):R117–R134. [PubMed]
  • Goto M, Kawano S, Yoshihara H, Takei Y, Hijioka T, Fukui H, Matsunaga T, Oshita M, Kashiwagi T, Fusamoto H, et al. Hepatic tissue oxygenation as a predictive indicator of ischemia-reperfusion liver injury. Hepatology. 1992 Mar;15(3):432–437. [PubMed]
  • Marubayashi S, Takenaka M, Dohi K, Ezaki H, Kawasaki T. Adenine nucleotide metabolism during hepatic ischemia and subsequent blood reflow periods and its relation to organ viability. Transplantation. 1980 Oct;30(4):294–296. [PubMed]
  • Wang WY, Taki Y, Morimoto T, Nishihira T, Yokoo N, Jikko A, Nishikawa K, Tanaka J, Kamiyama Y, Ozawa K. Effects of partial ischemia and reflow on mitochondrial metabolism in rat liver. Eur Surg Res. 1988;20(3):181–189. [PubMed]
  • Kamiike W, Nakahara M, Nakao K, Koseki M, Nishida T, Kawashima Y, Watanabe F, Tagawa K. Correlation between cellular ATP level and bile excretion in the rat liver. Transplantation. 1985 Jan;39(1):50–55. [PubMed]
  • Karwinski W, Husøy AM, Farstad M, Søreide O. Sixty minutes of normothermic ischemia in the rat liver: correlation between adenine nucleotides and bile excretion. J Surg Res. 1989 Feb;46(2):99–103. [PubMed]
  • Clemens MG, McDonagh PF, Chaudry IH, Baue AE. Hepatic microcirculatory failure after ischemia and reperfusion: improvement with ATP-MgCl2 treatment. Am J Physiol. 1985 Jun;248(6 Pt 2):H804–H811. [PubMed]
  • Post S, Palma P, Rentsch M, Gonzalez AP, Menger MD. Differential impact of Carolina rinse and University of Wisconsin solutions on microcirculation, leukocyte adhesion, Kupffer cell activity and biliary excretion after liver transplantation. Hepatology. 1993 Dec;18(6):1490–1497. [PubMed]
  • Vollmar B, Lang G, Menger MD, Messmer K. Hypertonic hydroxyethyl starch restores hepatic microvascular perfusion in hemorrhagic shock. Am J Physiol. 1994 May;266(5 Pt 2):H1927–H1934. [PubMed]
  • Arvidsson D, Svensson H, Haglund U. Laser-Doppler flowmetry for estimating liver blood flow. Am J Physiol. 1988 Apr;254(4 Pt 1):G471–G476. [PubMed]
  • Almond NE, Wheatley AM. Measurement of hepatic perfusion in rats by laser Doppler flowmetry. Am J Physiol. 1992 Feb;262(2 Pt 1):G203–G209. [PubMed]
  • Bowers BA, Branum GD, Rotolo FS, Watters CR, Meyers WC. Bile flow--an index of ischemic injury. J Surg Res. 1987 May;42(5):565–569. [PubMed]
  • Nishimura T, Yoshida Y, Watanabe F, Koseki M, Nishida T, Tagawa K, Kawashima Y. Blood level of mitochondrial aspartate aminotransferase as an indicator of the extent of ischemic necrosis of the rat liver. Hepatology. 1986 Jul-Aug;6(4):701–707. [PubMed]
  • Menger MD, Barker JH, Messmer K. Capillary blood perfusion during postischemic reperfusion in striated muscle. Plast Reconstr Surg. 1992 Jun;89(6):1104–1114. [PubMed]
  • Menger MD, Steiner D, Messmer K. Microvascular ischemia-reperfusion injury in striated muscle: significance of "no reflow". Am J Physiol. 1992 Dec;263(6 Pt 2):H1892–H1900. [PubMed]
  • Koo A, Komatsu H, Tao G, Inoue M, Guth PH, Kaplowitz N. Contribution of no-reflow phenomenon to hepatic injury after ischemia-reperfusion: evidence for a role for superoxide anion. Hepatology. 1992 Mar;15(3):507–514. [PubMed]
  • Marzi I, Knee J, Bühren V, Menger M, Trentz O. Reduction by superoxide dismutase of leukocyte-endothelial adherence after liver transplantation. Surgery. 1992 Jan;111(1):90–97. [PubMed]
  • Chien S. The Microcirculatory Society Eugene M. Landis Award lecture. Role of blood cells in microcirculatory regulation. Microvasc Res. 1985 Mar;29(2):129–151. [PubMed]
  • Braide M, Amundson B, Chien S, Bagge U. Quantitative studies on the influence of leukocytes on the vascular resistance in a skeletal muscle preparation. Microvasc Res. 1984 May;27(3):331–352. [PubMed]
  • Ferguson D, McDonagh PF, Biewer J, Paidas CN, Clemens MG. Spatial relationship between leukocyte accumulation and microvascular injury during reperfusion following hepatic ischemia. Int J Microcirc Clin Exp. 1993 Feb;12(1):45–60. [PubMed]
  • Leaf A. Cell swelling. A factor in ischemic tissue injury. Circulation. 1973 Sep;48(3):455–458. [PubMed]
  • Komatsu H, Koo A, Guth PH. Leukocyte flow dynamics in the rat liver microcirculation. Microvasc Res. 1990 Jul;40(1):1–13. [PubMed]
  • Rao PN, Walsh TR, Makowka L, Rubin RS, Weber T, Snyder JT, Starzl TE. Purine nucleoside phosphorylase: a new marker for free oxygen radical injury to the endothelial cell. Hepatology. 1990 Feb;11(2):193–198. [PMC free article] [PubMed]
  • Walsh TR, Rao PN, Makowka L, Starzl TE. Lipid peroxidation is a nonparenchymal cell event with reperfusion after prolonged liver ischemia. J Surg Res. 1990 Jul;49(1):18–22. [PMC free article] [PubMed]
  • McKeown CM, Edwards V, Phillips MJ, Harvey PR, Petrunka CN, Strasberg SM. Sinusoidal lining cell damage: the critical injury in cold preservation of liver allografts in the rat. Transplantation. 1988 Aug;46(2):178–191. [PubMed]

Articles from The American Journal of Pathology are provided here courtesy of American Society for Investigative Pathology


Save items

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...