The influence of preconditioning on metabolic changes in the pig liver before, during, and after warm liver ischemia measured by microdialysis

  • Anne-Sofie Kannerup
  • Henning Grønbæk
  • Peter Funch-Jensen
  • Rasmus Langelund Jørgensen
  • Frank Viborg Mortensen
Original Article



Ischemia-reperfusion injury induced by the Pringle maneuver is a well-known problem after liver surgery. The aim of this study was to monitor metabolic changes in the pig liver during warm ischemia and the following reperfusion preceded by ischemic preconditioning (IPC).


Eight Landrace pigs underwent laparotomy. Two microdialysis catheters were inserted in the liver, one in the left lobe and another in the right lobe. A reference catheter was inserted in the right biceps femoris muscle. Microdialysis samples were collected every 30 min during the study. After 2 h of baseline measurement, IPC was performed by subjecting pigs to 10 min of ischemia, followed by 10 min of reperfusion. Total ischemia for 60 min was followed by 3 h of reperfusion. The samples were analyzed for glucose, lactate, pyruvate, and glycerol. Blood samples were drawn three times to determine standard liver parameters.


All parameters remained stable during baseline. Glycerol and glucose levels increased significantly during ischemia, followed by a decrease from the start of reperfusion. During the ischemic period, lactate levels increased significantly and decreased during reperfusion. The lactate–pyruvate ratio increased significantly during ischemia and decreased rapidly during reperfusion. Only minor changes were observed in standard liver parameters.


The present study demonstrated profound metabolic changes before, during, and after warm liver ischemia under the influence of IPC. Compared with a similar study without IPC, the metabolic changes seem to be unaffected by preconditioning.


Warm liver ischemia Portal triad clamping Preconditioning Metabolic changes Microdialysis 


  1. 1.
    Jarnagin WR, Gonen M, Fong Y, Dematteo RP, Ben-Porat L, Little S, Corvera C, Weber S, Blumgart LH. Improvement in perioperative outcome after hepatic resection: analysis of 1,803 consecutive cases over the past decade. Ann Surg 2002;236:397–406PubMedCrossRefGoogle Scholar
  2. 2.
    Smyrniotis V, Arkadopoulos N, Kehagias D, Kostopanagiotou G, Scondras C, Kotsis T, Tsantoulas D. Liver resection with repair of major hepatic veins. Am J Surg 2002;183:58–61PubMedCrossRefGoogle Scholar
  3. 3.
    Hanazaki K, Monma T, Hiraguri M, Ohmoto Y, Kajikawa S, Matsushita A, Nimura Y, Koide N, Adachi W, Amano J. Cytokine response to human liver ischemia-reperfusion injury during hepatectomy: marker of injury or surgical stress? Hepatogastroenterology 2001;48:188–192PubMedGoogle Scholar
  4. 4.
    Jaeschke H. Molecular mechanisms of hepatic ischemia-reperfusion injury and preconditioning. Am J Physiol Gastrointest Liver Physiol 2003;284:G15–G26PubMedGoogle Scholar
  5. 5.
    Lee WY, Lee SM. Ischemic preconditioning protects post-ischemic oxidative damage to mitochondria in rat liver. Shock 2005;24:370–375. doi: 10.1097/ PubMedCrossRefGoogle Scholar
  6. 6.
    Peralta C, Hotter G, Closa D, Gelpi E, Bulbena O, Rosello-Catafau J. Protective effect of preconditioning on the injury associated to hepatic ischemia-reperfusion in the rat: role of nitric oxide and adenosine. Hepatology 1997;25:934–937. doi: 10.1002/hep.510250424 PubMedCrossRefGoogle Scholar
  7. 7.
    Kerem M, Bedirli A, Ofluoglu E, Deniz K, Turkozkan N, Pasaoglu H, et al. Ischemic preconditioning improves liver regeneration by sustaining energy metabolism after partial hepatectomy under ischemia in rats. Liver Int 2006;26:994–999. doi: 10.1111/j.1478-3231.2006.01330.x PubMedCrossRefGoogle Scholar
  8. 8.
    Ishii S, Abe T, Saito T, Tsuchiya T, Kanno H, Miyazawa M, et al. Effects of preconditioning on ischemia/reperfusion injury of hepatocytes determined by immediate early gene transcription. J Hepatobiliary Pancreat Surg 2001;8:461–468. doi: 10.1007/s005340100010 PubMedCrossRefGoogle Scholar
  9. 9.
    Hawaleshka A, Jacobsohn E. Ischaemic preconditioning: mechanisms and potential clinical applications. Can J Anaesth 1998;45:670–682PubMedGoogle Scholar
  10. 10.
    Rojdmark J, Blomqvist L, Malm M, Ms-Ray B, Ungerstedt U. Metabolism in myocutaneous flaps studied by in situ microdialysis. Scand J Plast Reconstr Surg Hand Surg 1998;32:27–34. doi: 10.1080/02844319850158921 PubMedCrossRefGoogle Scholar
  11. 11.
    Nowak G, Ungerstedt J, Wernerman J, Ungerstedt U, Ericzon BG. Metabolic changes in the liver graft monitored continuously with microdialysis during liver transplantation in a pig model. Liver Transpl 2002;8:424–432. doi: 10.1053/jlts.2002.32943 PubMedCrossRefGoogle Scholar
  12. 12.
    Nowak G, Ungerstedt J, Wernerson A, Ungerstedt U, Ericzon BG. Hepatic cell membrane damage during cold preservation sensitizes liver grafts to rewarming injury. J Hepatobiliary Pancreat Surg 2003;10:200–205. doi: 10.1007/s00534-002-0760-4 PubMedCrossRefGoogle Scholar
  13. 13.
    Liu DL, Jeppsson B, Hakansson CH, Odselius R. Multiple-system organ damage resulting from prolonged hepatic inflow interruption. Arch Surg 1996;131:442–447PubMedGoogle Scholar
  14. 14.
    Kannerup AS, Funch-Jensen P, Gronbaek H, Jorgensen RL, Mortensen FV. Metabolic changes in the pig liver during warm ischemia and reperfusion measured by microdialysis. J Gastrointest Surg 2008;12:319–326. doi: 10.1007/s11605-007-0359-9 PubMedCrossRefGoogle Scholar
  15. 15.
    Belghiti J, Di CI, Sauvanet A, Uribe M, Fekete F. A ten-year experience with hepatic resection in 338 patients: evolutions in indications and of operative mortality. Eur J Surg 1994;160:277–282PubMedGoogle Scholar
  16. 16.
    Elias D, Desruennes E, Lasser P. Prolonged intermittent clamping of the portal triad during hepatectomy. Br J Surg 1991;78:42–44. doi: 10.1002/bjs.1800780115 PubMedCrossRefGoogle Scholar
  17. 17.
    Man K, Fan ST, Ng IO, Lo CM, Liu CL, Wong J. Prospective evaluation of Pringle maneuver in hepatectomy for liver tumors by a randomized study. Ann Surg 1997;226:704–711. doi: 10.1097/00000658-199712000-00007 PubMedCrossRefGoogle Scholar
  18. 18.
    Muller M. Science, medicine, and the future: microdialysis. BMJ 2002;324:588–591. doi: 10.1136/bmj.324.7337.588 PubMedCrossRefGoogle Scholar
  19. 19.
    Hillered L, Persson L. Theory and practice of microdialysis—prospect for future clinical use. Acta Neurochir Suppl (Wien) 1999;75:3–6Google Scholar
  20. 20.
    Krejci V, Hiltebrand L, Buchi C, Ali SZ, Contaldo C, Takala J, et al. Decreasing gut wall glucose as an early marker of impaired intestinal perfusion. Crit Care Med 2006;34:2406–2414. doi: 10.1097/01.CCM.0000233855.34344.29 PubMedCrossRefGoogle Scholar
  21. 21.
    Hovda DA, Lee SM, Smith ML, Von SS, Bergsneider M, Kelly D, et al. The neurochemical and metabolic cascade following brain injury: moving from animal models to man. J Neurotrauma 1995;12:903–906PubMedCrossRefGoogle Scholar
  22. 22.
    Guinzberg R, Cortes D, Az-Cruz A, Riveros-Rosas H, Villalobos-Molina R, Pina E. Inosine released after hypoxia activates hepatic glucose liberation through A3 adenosine receptors. Am J Physiol Endocrinol Metab 2006;290:E940–E951. doi: 10.1152/ajpendo.00173.2005 PubMedCrossRefGoogle Scholar
  23. 23.
    Iu S, Harvey PR, Makowka L, Petrunka CN, Ilson RG, Strasberg SM. Markers of allograft viability in the rat. Relationship between transplantation viability and liver function in the isolated perfused liver. Transplantation 1987;44:562–569. doi: 10.1097/00007890-198710000-00021 PubMedCrossRefGoogle Scholar
  24. 24.
    Clavien PA, Yadav S, Sindram D, Bentley RC. Protective effects of ischemic preconditioning for liver resection performed under inflow occlusion in humans. Ann Surg 2000;232:155–162. doi: 10.1097/00000658-200008000-00001 PubMedCrossRefGoogle Scholar

Copyright information

© Asian Pacific Association for the Study of the Liver 2008

Authors and Affiliations

  • Anne-Sofie Kannerup
    • 1
  • Henning Grønbæk
    • 2
  • Peter Funch-Jensen
    • 1
  • Rasmus Langelund Jørgensen
    • 1
  • Frank Viborg Mortensen
    • 1
  1. 1.Department of Surgical Gastroenterology LAarhus University HospitalAarhus CDenmark
  2. 2.Department of Medical Gastroenterology VAarhus University HospitalAarhus CDenmark

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