| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
American Journal of Pathology, Vol 145, 1421-1431, Copyright © 1994 by American Society for Investigative Pathology
REGULAR ARTICLES |
B Vollmar, J Glasz, R Leiderer, S Post and MD Menger
Institute for Surgical Research, University of Munich, Germany.
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.
This article has been cited by other articles:
 |
|
 |
|
  J. D.W. van der Bilt, M. E. Soeters, A. M.M.J. Duyverman, M. W. Nijkamp, P. O. Witteveen, P. J. van Diest, O. Kranenburg, and I. H.M. Borel Rinkes Perinecrotic Hypoxia Contributes to Ischemia/Reperfusion-Accelerated Outgrowth of Colorectal Micrometastases Am. J. Pathol., April 1, 2007; 170(4): 1379 - 1388. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Raddatz, D. Kubulus, J. Winning, I. Bauer, S. Pradarutti, B. Wolf, S. Kreuer, and H. Rensing Dobutamine Improves Liver Function after Hemorrhagic Shock through Induction of Heme Oxygenase-1 Am. J. Respir. Crit. Care Med., July 15, 2006; 174(2): 198 - 207. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H.-J. Yu, B.-R. Lin, H.-S. Lee, C.-T. Shun, C.-C. Yang, T.-Y. Lai, C.-T. Chien, and S.-M. Hsu Sympathetic vesicovascular reflex induced by acute urinary retention evokes proinflammatory and proapoptotic injury in rat liver Am J Physiol Renal Physiol, May 1, 2005; 288(5): F1005 - F1014. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Chouker, A. Martignoni, R. Schauer, M. Dugas, H.-G. Rau, K.-W. Jauch, K. Peter, and M. Thiel Beneficial Effects of Ischemic Preconditioning in Patients Undergoing Hepatectomy: The Role of Neutrophils Arch Surg, February 1, 2005; 140(2): 129 - 136. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. A. Sutton, K. J. Kelly, H. E. Mang, Z. Plotkin, R. M. Sandoval, and P. C. Dagher Minocycline reduces renal microvascular leakage in a rat model of ischemic renal injury Am J Physiol Renal Physiol, January 1, 2005; 288(1): F91 - F97. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Chouker, T. Schachtner, R. Schauer, M. Dugas, F. Lohe, A. Martignoni, B. Pollwein, M. Niklas, H. G. Rau, K. W. Jauch, et al. Effects of Pringle manoeuvre and ischaemic preconditioning on haemodynamic stability in patients undergoing elective hepatectomy: a randomized trial Br. J. Anaesth., August 1, 2004; 93(2): 204 - 211. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Eipel, R. Bordel, R. M. Nickels, M. D. Menger, and B. Vollmar Impact of leukocytes and platelets in mediating hepatocyte apoptosis in a rat model of systemic endotoxemia Am J Physiol Gastrointest Liver Physiol, May 1, 2004; 286(5): G769 - G776. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Khandoga, A. Stampfl, S. Takenaka, H. Schulz, R. Radykewicz, W. Kreyling, and F. Krombach Ultrafine Particles Exert Prothrombotic but Not Inflammatory Effects on the Hepatic Microcirculation in Healthy Mice In Vivo Circulation, March 16, 2004; 109(10): 1320 - 1325. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. A. Sutton, H. E. Mang, S. B. Campos, R. M. Sandoval, M. C. Yoder, and B. A. Molitoris Injury of the renal microvascular endothelium alters barrier function after ischemia Am J Physiol Renal Physiol, August 1, 2003; 285(2): F191 - F198. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. SCHAFER, C. SCHEUER, K. ROEMER, M. D. MENGER, and B. VOLLMAR Inhibition of p53 protects liver tissue against endotoxin-induced apoptotic and necrotic cell death FASEB J, April 1, 2003; 17(6): 660 - 667. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Jaeschke Molecular mechanisms of hepatic ischemia-reperfusion injury and preconditioning Am J Physiol Gastrointest Liver Physiol, January 1, 2003; 284(1): G15 - G26. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Khandoga, G. Enders, P. Biberthaler, and F. Krombach Poly(ADP-ribose) polymerase triggers the microvascular mechanisms of hepatic ischemia-reperfusion injury Am J Physiol Gastrointest Liver Physiol, September 1, 2002; 283(3): G553 - G560. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Serafin, J. Rosello-Catafau, N. Prats, C. Xaus, E. Gelpi, and C. Peralta Ischemic Preconditioning Increases the Tolerance of Fatty Liver to Hepatic Ischemia-Reperfusion Injury in the Rat Am. J. Pathol., August 1, 2002; 161(2): 587 - 601. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Peralta, J. C. Perales, R. Bartrons, C. Mitchell, H. Gilgenkrantz, C. Xaus, N. Prats, L. Fernandez, E. Gelpi, J. Panes, et al. The Combination of Ischemic Preconditioning and Liver Bcl-2 Overexpression Is a Suitable Strategy to Prevent Liver and Lung Damage after Hepatic Ischemia-Reperfusion Am. J. Pathol., June 1, 2002; 160(6): 2111 - 2122. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Kobayashi, H. Imamura, M. Isobe, Y. Matsuyama, J. Soeda, K. Matsunaga, and S. Kawasaki Mac-1 (CD11b/CD18) and intercellular adhesion molecule-1 in ischemia-reperfusion injury of rat liver Am J Physiol Gastrointest Liver Physiol, August 1, 2001; 281(2): G577 - G585. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Man, C.-M. Lo, I. O.-L. Ng, Y.-C. Wong, L.-F. Qin, S.-T. Fan, and J. Wong Liver Transplantation in Rats Using Small-for-Size Grafts: A Study of Hemodynamic and Morphological Changes Arch Surg, March 1, 2001; 136(3): 280 - 285. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Nishida, S. Ueshima, H. Kazuo, T. Ito, A. Seiyama, and H. Matsuda Vagus nerve is involved in lack of blood reflow into sinusoids after rat hepatic ischemia Am J Physiol Heart Circ Physiol, May 1, 2000; 278(5): H1565 - H1570. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Kazuo, T. Nishida, A. Seiyama, S. Ueshima, E. Hamada, T. Ito, and H. Matsuda Recovery of blood flow and oxygen transport after temporary ischemia of rat liver Am J Physiol Heart Circ Physiol, July 1, 1998; 275(1): H243 - H249. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
