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.
References
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
Jakimowicz J, Stultiens G, Smulders F (1998) Laparoscopic insufflation of the abdomen reduces portal venous flow. Surg Endosc 12: 129–132
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
Richardson JD, Trinkle JK (1976) Hemodynamic and respiratory alterations with increased intraabdominal pressure. J Surg Res 20: 401–404
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
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
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
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
Caldwell CB, Ricotta JJ (1987) Changes in visceral blood flow with elevated intraabdominal pressure. J Surg Res 43: 14–20
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
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
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
Kotzampassi K, Kapanidis N, Kazamias P, Elefteriadis E (1993) Hemodynamic events in the peritoneal environment during pneumoperitoneum in dogs. Surg Endosc 7: 494–499
Morino M, Giraudo G, Festa V (1998) Alterations in hepatic function during laparoscopic surgery: an experimental clinical study. Surg Endosc 6: 968–972
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
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
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
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
Zulfikaroglu B, Koc M, Soran A, Isman FK, Cinel I (2002) Evaluation of oxidative stress in laparoscopic cholecystectomy. Surg Today 32: 869–874
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
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
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
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
Lemasters JJ, Thurman RG (1997) Reperfusion injury after liver preservation for transplantation. Annu Rev Pharmacol Toxicol 37: 327–338
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
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
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
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
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
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
Uhlmann S, Uhlmann D, Spiegel HU (1992) Evaluation of hepatic microcirculation by in vivo microscopy. J Invest Surg 12: 179–193
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
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
Eleftheriadis E, Kotzampassi K, Tzartinoglou E, Farmakis H, Dadoukis J (1996) Splanchnic ischemia during laparoscopic cholecystectomy. Surg Endosc 10: 324–326
Jakimowicz J, Stultiens G, Smulders F (1998) Laparoscopic insufflation of the abdomen reduces portal venous flow. Surg Endosc 12: 129–132
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
Schilling MK, Redaelli C, Krahenbuhl L, Signer C, Buchler MW (1997) Splanchnic microcirculatory changes during CO2 laparoscopy. J Am Coll Surg 184: 378–382
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
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
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
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
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
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
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
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
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
Bouwens L (1988) Structural and functional aspects of Kupffer cells. Revis Biol Celular 16: 69–94
Wardle EN (1987) Kupffer cells and their function. Liver 7: 63–75
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
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
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
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
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
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
Nolan JP (1981) Endotoxin, reticuloendothelial function, and liver injury. Hepatology 1: 458–465
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
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
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
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
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
Bzeizi KI, Jalan R, Plevris JN, Hayes PC (1997) Primary graft dysfunction after liver transplantation: from pathogenesis to prevention. Liver Transpl Surg 3: 137
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
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
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
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
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
Sato K, Kawamura T, Wakusawa R (2000) Hepatic blood flow and function in elderly patients undergoing laparoscopic cholecystectomy. Anesth Analg 90: 1198–1202
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
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
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
Jacobi CA, Sabat R, Böhm B, Zieren HU, Volk HD, Müller JM (1997) Pneumoperitoneum with CO2 stimulates malignant colonic cells. Surgery 121: 72–78
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
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
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
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
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
Selzner N, Rudiger H, Graf R, Clavien PA (2003) Protective strategies against ischemic injury of the liver. Gastroenterology 125(3): 917–936
Acknowledgment
The authors thank Genevieve Dei-Anane for editing the manuscript.
Author information
Authors and Affiliations
Corresponding author
Rights 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
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00464-007-9386-6