Skip to main content
SpringerLink
Log in

Interaction between anesthetic conditioning and ischemic preconditioning on metabolic function after hepatic ischemia–reperfusion in rabbits

  • Original Article
  • Published:
Journal of Anesthesia Aims and scope Submit manuscript

Abstract

Background

Both anesthetic-induced and ischemic preconditioning are protective against hepatic ischemia–reperfusion injury. However, the effects of these preventive methods on the metabolic function remain to be elucidated. We investigated the anesthetic conditioning and ischemic preconditioning on the metabolic function of the rabbit model of hepatic ischemia–reperfusion.

Methods

After approval by the institutional animal care and use committee, 36 Japanese White rabbits underwent partial hepatic ischemia for 90 min either under sevoflurane or propofol anesthesia. All the rabbits underwent 90 min of hepatic ischemia, and half of the rabbits in each group underwent additional 10-min ischemia and 10-min reperfusion before index ischemia. Hepatic microvascular blood flow was intermittently measured during reperfusion period, and galactose clearance, serum aminotransferase activities, and lactate concentrations were determined 180 min after reperfusion.

Results

Neither anesthetic conditioning with sevoflurane nor ischemic preconditioning altered hepatic microvascular blood flow during reperfusion and serum transaminase activities after reperfusion. However, galactose clearance of reperfused liver was significantly higher under sevoflurane anesthesia than propofol (0.016 ± 0.005/min vs. 0.011 ± 0.004/min). Statistically significant interaction between anesthetic choice and application of ischemic preconditioning suggests that the ischemic preconditioning is selectively protective under propofol anesthesia. Increase of blood lactate concentration was significantly suppressed under sevoflurane anesthesia compared to propofol (1.5 ± 0.8 vs. 3.9 ± 1.4 mmol/l) without any statistically significant interaction with the application of ischemic preconditioning.

Conclusion

Sevoflurane attenuated the decrease of galactose clearance and increase of the blood lactate after reperfusion compared to propofol. Application of ischemic preconditioning was significantly protective under propofol anesthesia.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Clavien PA, Petrowsky H, DeOliveira ML, Graf R. Strategies for safer liver surgery and partial liver transplantation. N Engl J Med. 2007;356:1545–59.

    Article  PubMed  Google Scholar 

  2. Vollmar B, Menger MD. The hepatic microcirculation: mechanistic contributions and therapeutic targets in liver injury and repair. Physiol Rev. 2009;89:1269–339.

    Article  PubMed  CAS  Google Scholar 

  3. Suyavaran A, Thirunavukkarasu C. Preconditioning methods in the management of hepatic ischemia reperfusion- induced injury: update on molecular and future perspectives. Hepatol Res. 2017;47:31–48.

    Article  PubMed  CAS  Google Scholar 

  4. 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;232:155–62.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  5. Clavien PA, Selzner M, Rudiger HA, Graf R, Kadry Z, Rousson V, Jochum W. A prospective randomized study in 100 consecutive patients undergoing major liver resection with versus without ischemic preconditioning. Ann Surg. 2003;238:843–52.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Chouker A, Martignoni A, Schauer R, Dugas M, Rau HG, Jauch KW, Peter K, Thiel M. Beneficial effects of ischemic preconditioning in patients undergoing hepatectomy: the role of neutrophils. Arch Surg. 2005;140:129–36.

    Article  PubMed  Google Scholar 

  7. Azoulay D, Lucidi V, Andreani P, Maggi U, Sebagh M, Ichai P, Lemoine A, Adam R, Castaing D. Ischemic preconditioning for major liver resection under vascular exclusion of the liver preserving the caval flow: a randomized prospective study. J Am Coll Surg. 2006;202:203–11.

    Article  PubMed  Google Scholar 

  8. Scatton O, Zalinski S, Jegou D, Compagnon P, Lesurtel M, Belghiti J, Boudjema K, Lentschener C, Soubrane O. Randomized clinical trial of ischaemic preconditioning in major liver resection with intermittent Pringle manoeuvre. Br J Surg. 2011;98:1236–43.

    Article  PubMed  CAS  Google Scholar 

  9. O’Neill S, Leuschner S, McNally SJ, Garden OJ, Wigmore SJ, Harrison EM. Meta-analysis of ischaemic preconditioning for liver resections. Br J Surg. 2013;100:1689–700.

    Article  PubMed  Google Scholar 

  10. Simillis C, Robertson FP, Afxentiou T, Davidson BR, Gurusamy KS. A network meta-analysis comparing perioperative outcomes of interventions aiming to decrease ischemia reperfusion injury during elective liver resection. Surgery. 2016;159:1157–69.

    Article  PubMed  Google Scholar 

  11. Chouker A, Schachtner T, Schauer R, Dugas M, Lohe F, Martignoni A, Pollwein B, Niklas M, Rau HG, Jauch KW, Peter K, Thiel M. Effects of Pringle manoeuvre and ischaemic preconditioning on haemodynamic stability in patients undergoing elective hepatectomy: a randomized trial. Br J Anaesth. 2004;93:204–11.

    Article  PubMed  CAS  Google Scholar 

  12. Beck-Schimmer B, Breitenstein S, Urech S, De Conno E, Wittlinger M, Puhan M, Jochum W, Spahn DR, Graf R, Clavien PA. A randomized controlled trial on pharmacological preconditioning in liver surgery using a volatile anesthetic. Ann Surg. 2008;248:909–18.

    Article  PubMed  Google Scholar 

  13. Beck-Schimmer B, Breitenstein S, Bonvini JM, Lesurtel M, Ganter M, Weber A, Puhan MA, Clavien PA. Protection of pharmacological postconditioning in liver surgery: results of a prospective randomized controlled trial. Ann Surg. 2012;256:837–45.

    Article  PubMed  Google Scholar 

  14. Song JC, Sun YM, Yang LQ, Zhang MZ, Lu ZJ, Yu WF. A comparison of liver function after hepatectomy with inflow occlusion between sevoflurane and propofol anesthesia. Anesth Analg. 2010;111:1036–41.

    PubMed  CAS  Google Scholar 

  15. Beck-Schimmer B, Bonvini JM, Schadde E, Dutkowski P, Oberkofler CE, Lesurtel M, DeOliveira ML, Figueira ER, Rocha Filho JA, Auler JO, D’Albuquerque LA, Reyntjens K, Wouters P, Rogiers X, Debaerdemaeker L, Ganter MT, Weber A, Puhan MA, Clavien PA, Breitenstein S. Conditioning with sevoflurane in liver transplantation: results of a multicenter randomized controlled trial. Transplantation. 2015;99:1606–12.

    Article  PubMed  CAS  Google Scholar 

  16. Montalvo-Jave EE, Escalante-Tattersfield T, Ortega-Salgado JA, Pina E, Geller DA. Factors in the pathophysiology of the liver ischemia-reperfusion injury. J Surg Res. 2008;147:153–9.

    Article  PubMed  CAS  Google Scholar 

  17. Klune JR, Tsung A. Molecular biology of liver ischemia/reperfusion injury: established mechanisms and recent advancements. Surg Clin North Am. 2010;90:665–77.

    Article  PubMed  Google Scholar 

  18. Yamada T, Kotake Y, Nagata H, Takeda J. Atrial natriuretic peptide reduces hepatic ischemia-reperfusion injury in rabbits. J Anesth. 2013;27:901–8.

    Article  PubMed  Google Scholar 

  19. Vollmar B, Glasz J, Leiderer R, Post S, Menger MD. Hepatic microcirculatory perfusion failure is a determinant of liver dysfunction in warm ischemia-reperfusion. Am J Pathol. 1994;145:1421–31.

    PubMed  PubMed Central  CAS  Google Scholar 

  20. Pannen BH. New insights into the regulation of hepatic blood flow after ischemia and reperfusion. Anesth Analg. 2002;94:1448–57.

    PubMed  CAS  Google Scholar 

  21. Glanemann M, Vollmar B, Nussler AK, Schaefer T, Neuhaus P, Menger MD. Ischemic preconditioning protects from hepatic ischemia/reperfusion-injury by preservation of microcirculation and mitochondrial redox-state. J Hepatol. 2003;38:59–66.

    Article  PubMed  CAS  Google Scholar 

  22. Bedirli N, Ofluoglu E, Kerem M, Utebey G, Alper M, Yilmazer D, Bedirli A, Ozlu O, Pasaoglu H. Hepatic energy metabolism and the differential protective effects of sevoflurane and isoflurane anesthesia in a rat hepatic ischemia-reperfusion injury model. Anesth Analg. 2008;106:830–7.

    Article  PubMed  CAS  Google Scholar 

  23. Machens HG, Pallua N, Mailaender P, Pasel J, Frank KH, Reimer R, Berger A. Measurements of tissue blood flow by the hydrogen clearance technique (HCT): a comparative study including laser Doppler flowmetry (LDF) and the Erlangen micro-lightguide spectrophotometer (EMPHO). Microsurgery. 1995;16:808–17.

    Article  PubMed  CAS  Google Scholar 

  24. Flynn WJ, Hoover EL. Allopurinol plus standard resuscitation preserves hepatic blood flow and function following hemorrhagic shock. J Trauma. 1994;37:956–61.

    Article  PubMed  CAS  Google Scholar 

  25. Annecke T, Kubitz JC, Kahr S, Hilberath JM, Langer K, Kemming GI, Rehm M, Bittmann I, Conzen PF. Effects of sevoflurane and propofol on ischaemia-reperfusion injury after thoracic-aortic occlusion in pigs. Br J Anaesth. 2007;98:581–90.

    Article  PubMed  CAS  Google Scholar 

  26. Kanda Y. Investigation of the freely available easy-to-use software ‘EZR’ for medical statistics. Bone Marrow Transplant. 2013;48:452–8.

    Article  PubMed  CAS  Google Scholar 

  27. Granja TF, Kohler D, Schad J, de Oliveira CB, Konrad F, Hoch-Gutbrod M, Streienberger A, Rosenberger P, Straub A. Adenosine receptor Adora2b plays a mechanistic role in the protective effect of the volatile anesthetic sevoflurane during liver ischemia/reperfusion. Anesthesiology. 2016;125:547–60.

    Article  PubMed  CAS  Google Scholar 

  28. Kadono J, Hamada N, Fukueda M, Ishizaki N, Kaieda M, Gejima K, Nishida S, Nakamura K, Yoshida H, Sakata R. Advantage of ischemic preconditioning for hepatic resection in pigs. J Surg Res. 2006;134:173–81.

    Article  PubMed  CAS  Google Scholar 

  29. Eichler K, Urner M, Twerenbold C, Kern S, Brugger U, Spahn DR, Beck-Schimmer B, Ganter MT. Economic evaluation of pharmacologic pre- and postconditioning with sevoflurane compared with total intravenous anesthesia in liver surgery: a cost analysis. Anesth Analg. 2017;124:925–33.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  30. Balzan SM, Gava VG, Rieger A, Pra D, Trombini L, Zenkner FF, Horta JA, Azambuja G, Schopf L, de Souza PL. Ischemic versus pharmacologic hepatic preconditioning. J Surg Res. 2014;191:134–9.

    Article  PubMed  CAS  Google Scholar 

  31. Rodriguez A, Taura P, Garcia Domingo MI, Herrero E, Camps J, Forcada P, Sabate S, Cugat E. Hepatic cytoprotective effect of ischemic and anesthetic preconditioning before liver resection when using intermittent vascular inflow occlusion: a randomized clinical trial. Surgery. 2015;157:249–59.

    Article  PubMed  Google Scholar 

  32. Orii R, Sugawara Y, Hayashida M, Uchida K, Yamada Y, Takayama T, Makuuchi M, Hanaoka K. Lactate is correlated with the indocyanine green elimination rate in liver resection for cirrhotic patients. Anesth Analg. 2001;92:1064–70.

    Article  PubMed  CAS  Google Scholar 

  33. Theodoraki K, Arkadopoulos N, Fragulidis G, Vassiliou I, Markatou M, Pafiti A, Kostopanagiotou G, Smyrniotis V. Ischemic preconditioning attenuates lactate release by the liver during hepatectomies under vascular control: a case-control study. J Gastrointest Surg. 2011;15:589–97.

    Article  PubMed  Google Scholar 

  34. Magorian T, Wood P, Caldwell J, Fisher D, Segredo V, Szenohradszky J, Sharma M, Gruenke L, Miller R. The pharmacokinetics and neuromuscular effects of rocuronium bromide in patients with liver disease. Anesth Analg. 1995;80:754–9.

    PubMed  CAS  Google Scholar 

  35. Jokinen MJ, Neuvonen PJ, Lindgren L, Hockerstedt K, Sjovall J, Breuer O, Askemark Y, Ahonen J, Olkkola KT. Pharmacokinetics of ropivacaine in patients with chronic end-stage liver disease. Anesthesiology. 2007;106:43–55.

    Article  PubMed  CAS  Google Scholar 

  36. Vibert E, Boleslawski E, Cosse C, Adam R, Castaing D, Cherqui D, Naili S, Regimbeau JM, Cunha AS, Truant S, Fleyfel M, Pruvot FR, Paugam-Burtz C, Farges O. Arterial lactate concentration at the end of an elective hepatectomy is an early predictor of the postoperative course and a potential surrogate of intraoperative events. Ann Surg. 2015;262:787–93.

    Article  PubMed  Google Scholar 

  37. Yang LQ, Tao KM, Liu YT, Cheung CW, Irwin MG, Wong GT, Lv H, Song JG, Wu FX, Yu WF. Remifentanil preconditioning reduces hepatic ischemia-reperfusion injury in rats via inducible nitric oxide synthase expression. Anesthesiology. 2011;114:1036–47.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

This study is supported by a JSPS KAKENHI Grant number JP13671614.

Author information

Authors and Affiliations

  1. Department of Anesthesiology, School of Medicine, Keio University, Tokyo, Japan

    Takashige Yamada, Hiromasa Nagata, Shizuko Kosugi, Takeshi Suzuki, Hiroshi Morisaki & Yoshifumi Kotake

  2. Department of Anesthesiology, Toho University Ohashi Medical Center, 2-17-6, Ohashi, Meguro, Tokyo, 153-8515, Japan

    Yoshifumi Kotake

Authors
  1. Takashige Yamada
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hiromasa Nagata
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shizuko Kosugi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Takeshi Suzuki
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hiroshi Morisaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yoshifumi Kotake
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yoshifumi Kotake.

Ethics declarations

Conflict of interest

The authors have no conflict of interest.

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yamada, T., Nagata, H., Kosugi, S. et al. Interaction between anesthetic conditioning and ischemic preconditioning on metabolic function after hepatic ischemia–reperfusion in rabbits. J Anesth 32, 599–607 (2018). https://doi.org/10.1007/s00540-018-2523-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00540-018-2523-7

Keywords

Search

Navigation