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.
Similar content being viewed by others
References
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
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
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
Jaeschke H. Molecular mechanisms of hepatic ischemia-reperfusion injury and preconditioning. Am J Physiol Gastrointest Liver Physiol 2003;284:G15–G26
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
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
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
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
Hawaleshka A, Jacobsohn E. Ischaemic preconditioning: mechanisms and potential clinical applications. Can J Anaesth 1998;45:670–682
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
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
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
Liu DL, Jeppsson B, Hakansson CH, Odselius R. Multiple-system organ damage resulting from prolonged hepatic inflow interruption. Arch Surg 1996;131:442–447
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
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
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
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
Muller M. Science, medicine, and the future: microdialysis. BMJ 2002;324:588–591. doi:10.1136/bmj.324.7337.588
Hillered L, Persson L. Theory and practice of microdialysis—prospect for future clinical use. Acta Neurochir Suppl (Wien) 1999;75:3–6
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
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
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
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
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
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
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
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12072-008-9104-z