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

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Abstract

Purpose

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).

Methods

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.

Results

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.

Conclusions

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.

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References

  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;236:397–406

    Article  PubMed  Google Scholar 

  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;183:58–61

    Article  PubMed  Google Scholar 

  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;48:188–192

    PubMed  CAS  Google Scholar 

  4. Jaeschke H. Molecular mechanisms of hepatic ischemia-reperfusion injury and preconditioning. Am J Physiol Gastrointest Liver Physiol 2003;284:G15–G26

    PubMed  CAS  Google Scholar 

  5. Lee WY, Lee SM. Ischemic preconditioning protects post-ischemic oxidative damage to mitochondria in rat liver. Shock 2005;24:370–375. doi:10.1097/01.shk.0000175895.33415.cd

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  9. Hawaleshka A, Jacobsohn E. Ischaemic preconditioning: mechanisms and potential clinical applications. Can J Anaesth 1998;45:670–682

    PubMed  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  Google Scholar 

  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

    Article  PubMed  Google Scholar 

  13. Liu DL, Jeppsson B, Hakansson CH, Odselius R. Multiple-system organ damage resulting from prolonged hepatic inflow interruption. Arch Surg 1996;131:442–447

    PubMed  CAS  Google Scholar 

  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

    Article  PubMed  Google Scholar 

  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;160:277–282

    PubMed  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  18. Muller M. Science, medicine, and the future: microdialysis. BMJ 2002;324:588–591. doi:10.1136/bmj.324.7337.588

    Article  PubMed  Google Scholar 

  19. Hillered L, Persson L. Theory and practice of microdialysis—prospect for future clinical use. Acta Neurochir Suppl (Wien) 1999;75:3–6

    CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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;12:903–906

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Anne-Sofie Kannerup.

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Kannerup, AS., Grønbæk, H., Funch-Jensen, P. et al. The influence of preconditioning on metabolic changes in the pig liver before, during, and after warm liver ischemia measured by microdialysis. Hepatol Int 3, 310–315 (2009). https://doi.org/10.1007/s12072-008-9104-z

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  • DOI: https://doi.org/10.1007/s12072-008-9104-z

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