Skip to main content

Advertisement

Log in

Signs of reperfusion injury following CO2 pneumoperitoneum: an in vivo microscopy study

Surgical Endoscopy Aims and scope Submit manuscript

Abstract

Background

During laparoscopic surgery, pneumoperitoneum is generally established by means of carbon dioxide (CO2) insufflation which may disturb hepatic microperfusion. It has been suggested that the desufflation at the end of the procedure creates a model of reperfusion in a previously ischemic liver, thus predisposing it to reperfusion injury.

Methods

To study the effects of pneumoperitoneum on hepatic microcirculation, Sprague-Dawley rats underwent pneumoperitoneum with an intraabdominal pressure of 8 or 12 mmHg for 90 min. Subsequently, in vivo microscopy was performed to assess intrahepatic microcirculation and transaminases were measured to index liver injury.

Results

A CO2 pneumoperitoneum of 8 mmHg did not change serum transaminases; however, further increase of intraperitoneal pressure to 12 mmHg significantly increased AST, ALT, and LDH measured after desufflation to almost 1.5 times as much as control values of 49 ± 5 U/L, 31 ± 3 U/L, and 114 ± 12 U/L. In parallel, in all subacinar zones the permanent adherence of both leukocytes and platelets to the endothelium increased by about sixfold and threefold, respectively. Furthermore, Kupffer cells labeled with latex beads as an index for their activation were significantly increased compared to controls.

Conclusion

This in vivo observation demonstrated traces of reperfusion injury in liver induced by the insufflation and desufflation of CO2 pneumoperitoneum. The clinical relevance of this finding and the issue of using hepatoprotective substances to prevent this injury should be further investigated.

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

Access this article

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.

References

  1. Schmandra TC, Kim ZG, Gutt CN (2001) Effect of insufflation gas and intraabdominal pressure on portal venous flow during pneumoperitoneum in the rat. Surg Endosc 15(4): 405–408

    Article  PubMed  CAS  Google Scholar 

  2. Jakimowicz J, Stultiens G, Smulders F (1998) Laparoscopic insufflation of the abdomen reduces portal venous flow. Surg Endosc 12: 129–132

    Article  PubMed  CAS  Google Scholar 

  3. Ivankovich AD, Miletich DJ, Albrecht MD, Heymann HJ, Bonnet RF (1975) Cardiovascular effects of intraperitoneal insufflation with carbon dioxide and nitrous oxide in the dog. Anesthesiology 42: 281–287

    Article  PubMed  CAS  Google Scholar 

  4. Richardson JD, Trinkle JK (1976) Hemodynamic and respiratory alterations with increased intraabdominal pressure. J Surg Res 20: 401–404

    Article  PubMed  CAS  Google Scholar 

  5. Wittgen CM, Andrus CH, Fitzgerald SD, Baudendistel LJ, Dahms TE, Kaminski DL (1991) Analysis of the hemodynamic and ventilatory effects of laparoscopic cholecystectomy. Arch Surg 126: 997–1000

    PubMed  CAS  Google Scholar 

  6. Cisek LJ, Gobet RM, Peters CA (1998) Pneumoperitoneum produces reversible renal dysfunction in animals with normal and chronically reduced renal function. J Endourol 12: 95–100

    PubMed  CAS  Google Scholar 

  7. Leighton T, Pianim N, Liu S, Kono M, Klein S, Bongard F (1992) Effectors of hypercarbia during experimental pneumoperitoneum. Am J Surg 58: 717–721

    CAS  Google Scholar 

  8. Ho HS, Saunders CJ, Gunther RA, Wolfe BM (1995) Effector of hemodynamics during laparoscopy: CO2 absorption or intraabdominal pressure? J Surg Res 59: 497–503

    Article  PubMed  CAS  Google Scholar 

  9. Caldwell CB, Ricotta JJ (1987) Changes in visceral blood flow with elevated intraabdominal pressure. J Surg Res 43: 14–20

    PubMed  CAS  Google Scholar 

  10. Diebel LN, Wilson RF, Dulchavsky SA, Saxe J (1992) Effect of increased intraabdominal pressure on hepatic arterial, portal venous and hepatic microcirculatory blood flow. J Trauma 33: 279–282

    Article  PubMed  CAS  Google Scholar 

  11. Shimizu M, Hiroshi Y, Hatori N, Hag Y, Okuda E, Uriuda Y, Tanaka S (1990) Acute effect of intraabdominal presure on liver and systemic circulation. Vasc Surg 24: 677–682

    Google Scholar 

  12. Ishizaki Y, Bandai Y, Shimomura K, Abe H, Ohtomo Y, Idezuki Y (1993) Changes in splanchnic blood flow and cardiovascular effects following peritoneal insufflation of carbon dioxide. Surg Endosc 7: 420–423

    Article  PubMed  CAS  Google Scholar 

  13. Kotzampassi K, Kapanidis N, Kazamias P, Elefteriadis E (1993) Hemodynamic events in the peritoneal environment during pneumoperitoneum in dogs. Surg Endosc 7: 494–499

    Article  PubMed  CAS  Google Scholar 

  14. Morino M, Giraudo G, Festa V (1998) Alterations in hepatic function during laparoscopic surgery: an experimental clinical study. Surg Endosc 6: 968–972

    Article  Google Scholar 

  15. Gutt CN, Kuntz C, Schmandra T, Wunsch A, Heinz P, Bouvy N, Bessler M, Sanger P, Bonjer J, Allendorf J, Jacobi CA, Whelan R (1998) Metabolism and immunology in laparoscopy. First workshop on experimental laparoscopic surgery, Frankfurt, 1997. Surg Endosc 12(8): 1096–1098

    Article  PubMed  CAS  Google Scholar 

  16. Kim ZG, Mehl C, Lorenz M, Gutt CN (2002) Impact of laparoscopic CO2 insufflation on tumor-associated molecules in cultured colorectal cancer cells. Surg Endosc 16(8): 1182–1186

    Article  PubMed  CAS  Google Scholar 

  17. Gutt CN, Riemer V, Kim ZG, Erceg J, Lorenz M (2001) Impact of laparoscopic surgery on experimental hepatic metastases. Br J Surg 88(3): 371–375

    Article  PubMed  CAS  Google Scholar 

  18. Ishida H, Murata N, Yamada H, Nomura T, Shimomura K, Fujioka M, Idezuki M (2000) Effect of CO2 pneumoperitoneum on growth of liver micrometastases in a rabbit model. World J Surg 24: 1004–1008

    Article  PubMed  CAS  Google Scholar 

  19. Zulfikaroglu B, Koc M, Soran A, Isman FK, Cinel I (2002) Evaluation of oxidative stress in laparoscopic cholecystectomy. Surg Today 32: 869–874

    Article  PubMed  CAS  Google Scholar 

  20. Sare M, Hamamci D, Yilmaz I, Birincioglu M, Mentes BB, Ozmen M, Yesilada O (2002) Effects of carbon dioxide pneumoperitoneum on free radical formation in lung and liver tissues. Surg Endosc 16(1): 188–192

    Article  PubMed  CAS  Google Scholar 

  21. Malter M, Friedrich E, Suss R (1986) Liver as a tumor cell killing organ: Kupffer cells and natural killers. Cancer Res 46(6): 3055–3060

    PubMed  CAS  Google Scholar 

  22. Curley SA, Roh MS, Feig B, Oyedeji C, Kleinerman ES, Klostergaard J (1993) Mechanisms of Kupffer cell cytotoxicity in vitro against the syngeneic murine colon adenocarcinoma line MCA26. J Leukoc Biol 53(6): 715–721

    PubMed  CAS  Google Scholar 

  23. Roh MS, Kahky MP, Oyedeji C, Klostergaard J, Wang L, Curley SA, Lotzova E (1992) Murine Kupffer cells and hepatic natural killer cells regulate tumor growth in a quantitative model of colorectal liver metastases. Clin Exp Metastasis 10(5): 317–327

    Article  PubMed  CAS  Google Scholar 

  24. Lemasters JJ, Thurman RG (1997) Reperfusion injury after liver preservation for transplantation. Annu Rev Pharmacol Toxicol 37: 327–338

    Article  PubMed  CAS  Google Scholar 

  25. Thurman RG, Marzi I, Seitz G, Thies J, Lemasters JJ, Zimmermann FA (1988) Hepatic reperfusion injury following orthotopic liver transplantation in the rat. Transplantation 46: 502–506

    Article  PubMed  CAS  Google Scholar 

  26. Schemmer P, Enomoto N, Bradford BU, Bunzendahl H, Raleigh JA, Lemasters JJ, Thurman RG (2001) Activated Kupffer cells cause a hypermetabolic state after gentle in situ manipulation of liver in rats. Am J Physiol 280: G1076–G1082

    CAS  Google Scholar 

  27. Schemmer P, Barro-Bejarano M, Mehrabi A, Gebhard MM, Kraus T, Büchler MW, Gutt CN (2005). Laparoscopic organ retrieval for living donor liver transplantation does not prevent graft injury. Transplant Proc 37(3): 1625–1627

    Article  PubMed  CAS  Google Scholar 

  28. Gutt CN, Held S, Heller K, Paolucci V (1996) A small animal model for laparoscopic microsurgery training. Min Invas Ther Allied Technol 5: 302–306

    Article  Google Scholar 

  29. Menger MD, Marzi I, Messmer K (1991) In vivo fluorescence microscopy for quantitative analysis of the hepatic microcirculation in hamsters and rats. Eur Surg Res 23: 158–169

    PubMed  CAS  Google Scholar 

  30. Post S, Palma P, Rentsch M, Gonzalez AP, Menger MD (1993) Differential impact of Carolina rinse and University of Wisconsin solutions on microcirculation, leukocyte adhesion, Kupffer cell activity and biliary excretion after liver transplantation. Hepatology 18: 1490

    PubMed  CAS  Google Scholar 

  31. Uhlmann S, Uhlmann D, Spiegel HU (1992) Evaluation of hepatic microcirculation by in vivo microscopy. J Invest Surg 12: 179–193

    Article  Google Scholar 

  32. Kuntz C, Wunsch A, Bodeker C, Bay F, Rosch R, Windeler J, Herfarth C (2000) Effect of pressure and gas type on intraabdominal, subcutaneous, and blood pH in laparoscopy. Surg Endosc 14(4): 367–371

    Article  PubMed  CAS  Google Scholar 

  33. Gutt CN, Kim ZG, Hollander D, Bruttel T, Lorenz M (2001) CO2 environment influences the growth of cultured human cancer cells dependent on insufflation pressure. Surg Endosc 15(3): 314–318

    Article  PubMed  CAS  Google Scholar 

  34. Eleftheriadis E, Kotzampassi K, Tzartinoglou E, Farmakis H, Dadoukis J (1996) Splanchnic ischemia during laparoscopic cholecystectomy. Surg Endosc 10: 324–326

    Article  PubMed  CAS  Google Scholar 

  35. Jakimowicz J, Stultiens G, Smulders F (1998) Laparoscopic insufflation of the abdomen reduces portal venous flow. Surg Endosc 12: 129–132

    Article  PubMed  CAS  Google Scholar 

  36. Diebel LN, Wilson RF, Dulchavsky SA, Saxe J (1992) Effect of increased intraabdominal pressure on hepatic arterial, portal venous, and hepatic microcirculatory blood flow. J Trauma 33: 279–283

    Article  PubMed  CAS  Google Scholar 

  37. Schilling MK, Redaelli C, Krahenbuhl L, Signer C, Buchler MW (1997) Splanchnic microcirculatory changes during CO2 laparoscopy. J Am Coll Surg 184: 378–382

    PubMed  CAS  Google Scholar 

  38. Eleftheriadis E, Kotzampassi K, Papanotas K, Heliadis N, Sarris K (1996) Gut ischemia, oxidative stress, and bacterial translocation in elevated abdominal pressure in rats. World J Surg 20(1): 11–16

    Article  PubMed  CAS  Google Scholar 

  39. Glantzounis GK, Tselepis AD, Tambaki AP, Trikalinos TA, Manataki AD, Galaris DA, Tsimoyiannis EC, Kappas AM (2001) Laparoscopic surgery-induced changes in oxidative stress markers in human plasma. Surg Endosc 15: 1315–1319

    Article  PubMed  CAS  Google Scholar 

  40. Vollmar B, Glasz J, Leiderer R, Post S, Menger MD (1994) Hepatic microcirculatory perfusion failure is a determinant for liver dysfunction in warm ischemia-reperfusion. Am J Pathol 145: 1–11

    Google Scholar 

  41. Bremer C, Bradford BU, Hunt KJ, Knecht KT, Connor HD, Mason RP, Thurman RG (1994) Role of Kupffer cells in the pathogenesis of hepatic reperfusion injury. Am J Physiol 267: G630–G636

    PubMed  CAS  Google Scholar 

  42. Marzi I, Knee J, Menger MD, Harbauer G, Buhren V (1991) Hepatic microcirculatory disturbances due to portal vein clamping in the orthotopic rat liver transplantation model. Transplantation 52: 432–436

    Article  PubMed  CAS  Google Scholar 

  43. Thurman RG, Marzi I, Seitz G, Thies J, Lemasters JJ, Zimmermann FA (1988) Hepatic reperfusion injury following orthotopic liver transplantation in the rat. Transplantation 46: 502–506

    Article  PubMed  CAS  Google Scholar 

  44. Gao W, Takei Y, Marzi I, Lindert KA, Caldwell-Kenkel JC, Currin RT, Tanaka Y, Lemasters JJ, Thurman RG (1991) Carolina rinse solution: A new strategy to increase survival time after orthotopic liver transplantation in the rat. Transplantation 52: 417–424

    Article  PubMed  CAS  Google Scholar 

  45. Takei Y, Marzi I, Gao W, Gores GJ, Lemasters JJ, Thurman RG (1991) Leukocyte adhesion and cell death following orthotopic liver transplantation in the rat. Transplantation 51: 959–965

    Article  PubMed  CAS  Google Scholar 

  46. Caldwell-Kenkel JC, Thurman RG, Lemasters JJ (1988) Selective loss of nonparenchymal cell viability after cold ischemic storage of rat livers. Transplantation 45: 834–837

    Article  PubMed  CAS  Google Scholar 

  47. Bouwens L (1988) Structural and functional aspects of Kupffer cells. Revis Biol Celular 16: 69–94

    PubMed  CAS  Google Scholar 

  48. Wardle EN (1987) Kupffer cells and their function. Liver 7: 63–75

    PubMed  CAS  Google Scholar 

  49. Bremer C, Bradford BU, Hunt KJ, Knecht KT, Connor HD, Mason RP, Thurman RG (1994) Role of Kupffer cells in the pathogenesis of hepatic reperfusion injury. Am J Physiol 267: G630–G636

    PubMed  CAS  Google Scholar 

  50. Ala A, Dhillon AP, Hodgson HJ (2003) Role of cell adhesion molecules in leukocyte recruitment in the liver and gut. Int J Exp Pathol 84: 1–16

    Article  PubMed  CAS  Google Scholar 

  51. Wunsch A (1997) Influence of different gases used for insufflation on the pH of subcutaneous tissue. First Workshop on experimental laparoscopic surgery, Frankfurt, 7–8 March, 1997, section: Metabolism and immunology in laparoscopy, Surg Endosc 12: 1096–1098

    Google Scholar 

  52. Gutt CN, Heinz P, Kaps W, Paolucci V (1997) The phagocytosis activity during conventional and laparoscopic operations in the rat: a preliminary study. Surg Endosc 11: 899–901

    Article  PubMed  CAS  Google Scholar 

  53. Widmann JJ, Cotran RS, Fahimi HD (1972) Mononuclear phagocytes (Kupffer cells) and endothelial cells. Identification of two functional cell types in rat liver sinusoids by endogenous peroxidase activity. J Cell Biol 52: 159–170

    Article  PubMed  CAS  Google Scholar 

  54. Yano H, Kinoshita S, Kira S (2004) Effects of acute moderate exercise on the phagocytosis of Kupffer cells in rats. Acta Physiol Scand 182(2): 151–160

    Article  PubMed  CAS  Google Scholar 

  55. Nolan JP (1981) Endotoxin, reticuloendothelial function, and liver injury. Hepatology 1: 458–465

    Article  PubMed  CAS  Google Scholar 

  56. Cowper KB, Currin RT, Dawson TL, Lindert KA, Lemasters JJ, Thurman RG (1990) A new method to monitor Kupffer-cell function continuously in the perfused rat liver: dissociation of glycogenolysis from particle phagocytosis. Biochem J 266: 141–147

    PubMed  CAS  Google Scholar 

  57. Monden K, Arii S, Itai S, Sasaoki T, Adachi Y, Funaki N, Tobe T (1991) Enhancement of hepatic macrophages in septic rats and their inhibitory effect on hepatocyte function. J Surg Res 50: 72–76

    Article  PubMed  CAS  Google Scholar 

  58. Schultze RL,Gangopadhyay A,Cay O,Lazure D, Thomas P (1999) Tyrosine kinase activation in LPS stimulates rat Kupffer cells. Cell Biochem Biophys 30: 287–301

    Article  PubMed  CAS  Google Scholar 

  59. Tokyay R, Zeigler ST, Traber DL, Stothert JC Jr, Loick HM, Heggers JP, Herndon DN (1993) Postburn gastrointestinal vasoconstriction increases bacterial and endotoxin translocation. J Appl Physiol 74: 1521–1527

    Article  PubMed  CAS  Google Scholar 

  60. Morris SE, Navaratnam N, Townsend CM, Herndon DN (1989) Decreased mesenteric blood flow independently promotes bacterial translocation in chronically instrumented sheep. Surg Forum 40: 88–90

    Google Scholar 

  61. Bzeizi KI, Jalan R, Plevris JN, Hayes PC (1997) Primary graft dysfunction after liver transplantation: from pathogenesis to prevention. Liver Transpl Surg 3: 137

    Article  PubMed  CAS  Google Scholar 

  62. Sakamoto M, Ueno T, Kin M, Ohira H, Torimura T, Inuzuka S, Sata M, Tanikawa K (1993) Ito cell contraction in response to endothelin-1 and substance P. Hepatology 18: 978

    Article  PubMed  CAS  Google Scholar 

  63. Halevy A, Gold-Deutch A, Negri M, Lin G, Shlamkovich N, Evans S, Cotariu D, Scapa E, Bahar M, Sackier JM (1994) Are elevated liver enzymes and bilirubin levels significant after laparoscopic cholecystectomy in the absence of bile duct injury? Ann Surg 219: 362–264

    Article  PubMed  CAS  Google Scholar 

  64. Sala-Blanch X, Fontanals J, Martinez-Palli G, Taura P, Delgado S, Bosch J, Lacy AM, Visa J (1998) Effects of carbon dioxide vs helium pneumoperitoneum on hepatic blood flow. Surg Endosc 12: 1121–1125

    Article  PubMed  CAS  Google Scholar 

  65. Kotake Y, Takeda J, Matsumoto M, Tagawa M, Kikuchi H (2001) Subclinical hepatic dysfunction in laparoscopic cholecystectomy and laparoscopic colectomy. Br J Anaesth 87: 774–777

    Article  PubMed  CAS  Google Scholar 

  66. Andrei VE, Schein M, Margolis M, Rucinski JC, Wise L (1998) Liver enzymes are commonly elevated following laparoscopic cholecystectomy: is elevated intraabdominal pressure the cause? Dig Surg 15: 256–259

    Article  PubMed  CAS  Google Scholar 

  67. Sato K, Kawamura T, Wakusawa R (2000) Hepatic blood flow and function in elderly patients undergoing laparoscopic cholecystectomy. Anesth Analg 90: 1198–1202

    Article  PubMed  CAS  Google Scholar 

  68. Min Tan, Feng-Feng Xu, Jun-Shen Peng, Dong-Ming Li, Liu-Hua Chen, Bao-Jun Lv, Zhen-Xian Zhao, Chen Huang, Chao-Xu Zheng (2003) Changes in the level of serum liver enzymes after laparoscopic surgery. World J Gastroenterol 9(2): 364–367

  69. Gutt CN, Gessmann T, Schemmer P, Mehrabi A, Schmandra T, Kim ZG (2003) The impact of carbon dioxide and helium insufflation on experimental liver metastases, macrophages, and cell adhesion molecules. Surg Endosc 17(10): 1628–1631

    Article  PubMed  CAS  Google Scholar 

  70. Jacobi CA, Wenger F, Sabat R, Volk T, Ordemann J, Müller JM (1998) The impact of laparoscopy with carbon dioxide versus helium on immunologic function and tumor growth in a rat model. Dig Surg 15(2): 110–116

    Article  PubMed  CAS  Google Scholar 

  71. Jacobi CA, Sabat R, Böhm B, Zieren HU, Volk HD, Müller JM (1997) Pneumoperitoneum with CO2 stimulates malignant colonic cells. Surgery 121: 72–78

    Article  PubMed  CAS  Google Scholar 

  72. Cherqui D, Soubrane O, Husson E, Barshasz E, Vignaux O, Ghimouz M, Branchereau S, Chardot C, Gauthier F, Fagniez PL, Houssin D (2002) Laparoscopic living donor hepatectomy for liver transplantation in children. Lancet 359 (9304): 392–396

    Article  PubMed  Google Scholar 

  73. Lin E, Gonzalez R, Venkatesh KR, Mattar SG, Bowers SP, Fugate KM, Heffron TG, Smith CD (2003) Can current technology be integrated to facilitate laparoscopic living donor hepatectomy? Surg Endosc 17(5): 750–753

    Article  PubMed  CAS  Google Scholar 

  74. Sare M, Hamamci D, Yilmaz I, Birincioglu M, Mentes BB, Ozmen M, Yesilada O (2002) Effects of carbon dioxide pneumoperitoneum on free radical formation in lung and liver tissues. Surg Endosc 16(1): 188–192

    Article  PubMed  CAS  Google Scholar 

  75. Puhl G, Schaser KD, Pust D, Kohler K, Vollmar B, Menger MD, Neuhaus P, Settmacher U (2005) Initial hepatic microcirculation correlates with early graft function in human orthotopic liver transplantation. Liver Transpl 11(5): 555–563

    Article  PubMed  Google Scholar 

  76. Rudiger HA, Kang KJ, Sindram D, Riehle HM, Clavien PA (2002) Comparison of ischemic preconditioning and intermittent and continuous inflow occlusion in the murine liver. Ann Surg 235(3): 400–407

    Article  PubMed  Google Scholar 

  77. Selzner N, Rudiger H, Graf R, Clavien PA (2003) Protective strategies against ischemic injury of the liver. Gastroenterology 125(3): 917–936

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgment

The authors thank Genevieve Dei-Anane for editing the manuscript.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Peter Schemmer.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Nickkholgh, A., Barro-Bejarano, M., Liang, R. et al. Signs of reperfusion injury following CO2 pneumoperitoneum: an in vivo microscopy study. Surg Endosc 22, 122–128 (2008). https://doi.org/10.1007/s00464-007-9386-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00464-007-9386-6

Keywords

Navigation