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Full length article| Volume 265, P107-112, October 2021

Pneumoperitoneum induced mesothelial cell changes in a laparoscopic mouse model

  • Author Footnotes
    1 Present affiliation: Rommel Consulting Partners SRL. Rue de Fonteny 12, B1370 Jodoigne, Belgium.
    Maria Mercedes Binda
    Correspondence
    Corresponding author.
    Footnotes
    1 Present affiliation: Rommel Consulting Partners SRL. Rue de Fonteny 12, B1370 Jodoigne, Belgium.
    Affiliations
    Department of Obstetrics and Gynaecology, University Hospital Gasthuisberg, Katholieke Universiteit Leuven (KULeuven), Leuven, Belgium
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  • Author Footnotes
    2 Present affiliation: Maigaard Fertility Clinic, Aarhus N, Denmark.
    Mads Riiskjaer
    Footnotes
    2 Present affiliation: Maigaard Fertility Clinic, Aarhus N, Denmark.
    Affiliations
    Department of Obstetrics and Gynaecology, University Hospital Gasthuisberg, Katholieke Universiteit Leuven (KULeuven), Leuven, Belgium
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  • Author Footnotes
    3 Present affiliation: Latifa Hospital, Dubai, United Arab Emirates; Professor Emeritus OBGYN, KULeuven Belgium; University of Oxford-Hon Consultant, UK; University Cattolica, Roma, Italy; Moscow State University, Russia; Gruppo Italo Belga, Villa Del Rosario Rome, Italy.
    Philippe Robert Koninckx
    Footnotes
    3 Present affiliation: Latifa Hospital, Dubai, United Arab Emirates; Professor Emeritus OBGYN, KULeuven Belgium; University of Oxford-Hon Consultant, UK; University Cattolica, Roma, Italy; Moscow State University, Russia; Gruppo Italo Belga, Villa Del Rosario Rome, Italy.
    Affiliations
    Department of Obstetrics and Gynaecology, University Hospital Gasthuisberg, Katholieke Universiteit Leuven (KULeuven), Leuven, Belgium
    Search for articles by this author
  • Author Footnotes
    1 Present affiliation: Rommel Consulting Partners SRL. Rue de Fonteny 12, B1370 Jodoigne, Belgium.
    2 Present affiliation: Maigaard Fertility Clinic, Aarhus N, Denmark.
    3 Present affiliation: Latifa Hospital, Dubai, United Arab Emirates; Professor Emeritus OBGYN, KULeuven Belgium; University of Oxford-Hon Consultant, UK; University Cattolica, Roma, Italy; Moscow State University, Russia; Gruppo Italo Belga, Villa Del Rosario Rome, Italy.

      Abstract

      Background

      CO2 pneumoperitoneum (PP) during laparoscopic surgery, can cause hypoxia and desiccation in the peritoneal mesothelial cell, resulting in a time-dependent retraction and bulging of these cells, an acute inflammatory reaction and enhanced adhesion formation. Since hypoxia is prevented by adding 4% of oxygen (O2) to the CO2 PP, the aim of this study was to evaluate the effect of adding 4% O2 to the CO2 PP on mesothelial cell morphology.

      Methods

      In a standardized laparoscopic mouse model (n=8 mice per group), a control group with a 30- or 60-min PP with humidified CO2 + 4% of O2 (groups I and II) was compared to a hypoxic group with 30- or 60-min humidified pure CO2 (groups III and IV) and a desiccation group with 60-min of dry CO2 PP (group V). The effect upon the peritoneum morphology was evaluated by scanning electron microscopy (SEM) of abdominal wall peritoneal biopsies. Biopsies, taken immediately (n=4) and 24 hrs (n=4) after surgery, were compared to a group without PP (group VI, n=4). SEM pictures were blindly scored for cell retraction, deletion of microvilli, fibrin deposition, holes in the epithelial layer and visibility of cell borders using a semi-quantitative scoring system.

      Results

      PP Hypoxia (CO2 PP) has a deleterious effect upon mesothelial morphology, immediately (holes: p= 0.04) and 24 hrs later (cell retraction: p=0.005; total score: p=0.03) . Desiccation has also a deleterious effect immediately (microvilli p=0.0090; fibrin deposition p=0.05) and 24 hrs after surgery (cell retraction: p=0.0036; holes: p=0.0004; microvilli: p< 0.0001, fibrin deposition: p=0.0225; borders: p=0.0007). This deleterious effect increases with duration of CO2 PP, affecting cell retraction (p=0.016), holes (p=0.0441), and the total score (p=0.0488). The addition of 4% of O2 to the CO2 PP failed to reach statistical significance.

      Conclusions

      These data confirm that CO2 PP and dry gas have a deleterious effect on mesothelial cell morphology. Humidification of the insufflation gas reduces this deleterious effect. The hypothesis of a protective effect of adding O2 failed to reach significance.

      Keywords

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      References

        • Binda M.M.
        Humidification during laparoscopic surgery: overview of the clinical benefits of using humidified gas during laparoscopic surgery.
        Arch Gynecol Obstet. 2015; 292: 955-971https://doi.org/10.1007/s00404-015-3717-y
        • Molinas C.R.
        • Mynbaev O.
        • Pauwels A.n.
        • Novak P.
        • Koninckx P.R.
        Peritoneal mesothelial hypoxia during pneumoperitoneum is a cofactor in adhesion formation in a laparoscopic mouse model.
        Fertil Steril. 2001; 76: 560-567https://doi.org/10.1016/S0015-0282(01)01964-1
        • Corona R.
        • Verguts J.
        • Schonman R.
        • Binda M.M.
        • Mailova K.
        • Koninckx P.R.
        Postoperative inflammation in the abdominal cavity increases adhesion formation in a laparoscopic mouse model.
        Fertil Steril. 2011; 95: 1224-1228https://doi.org/10.1016/j.fertnstert.2011.01.004
        • Elkelani O.A.
        • Binda M.M.
        • Molinas C.R.
        • Koninckx P.R.
        Effect of adding more than 3% oxygen to carbon dioxide pneumoperitoneum on adhesion formation in a laparoscopic mouse model.
        Fertil Steril. 2004; 82: 1616-1622https://doi.org/10.1016/j.fertnstert.2004.07.933
        • Molinas C.R.
        • Campo R.
        • Elkelani O.A.
        • Binda M.M.
        • Carmeliet P.
        • Koninckx P.R.
        Role of hypoxia inducible factors 1α and 2α in basal adhesion formation and in carbon dioxide pneumoperitoneum-enhanced adhesion formation after laparoscopic surgery in transgenic mice.
        Fertil Steril. 2003; 80: 795-802https://doi.org/10.1016/S0015-0282(03)00779-9
        • Binda M.M.
        • Molinas C.R.
        • Bastidas A.
        • Jansen M.
        • Koninckx P.R.
        Efficacy of barriers and hypoxia-inducible factor inhibitors to prevent CO2 pneumoperitoneum-enhanced adhesions in a laparoscopic mouse model.
        J Minim Invasive Gynecol. 2007; 14https://doi.org/10.1016/j.jmig.2007.04.002
        • Strowitzki M.J.
        • Ritter A.S.
        • Radhakrishnan P.
        • Harnoss J.M.
        • Opitz V.M.
        • Biller M.
        • et al.
        Pharmacological HIF-inhibition attenuates postoperative adhesion formation.
        Sci Rep. 2017; 7https://doi.org/10.1038/s41598-017-13638-z
        • Braun K.M.
        • Diamond M.P.
        The biology of adhesion formation in the peritoneal cavity.
        Semin Pediatr Surg. 2014; 23: 336-343https://doi.org/10.1053/j.sempedsurg.2014.06.004
        • Binda M.M.
        • Molinas C.R.
        • Hansen P.
        • Koninckx P.R.
        Effect of desiccation and temperature during laparoscopy on adhesion formation in mice.
        Fertil Steril. 2006; 86: 166-175https://doi.org/10.1016/j.fertnstert.2005.11.079
        • Volz J.
        • Köster S.
        • Spacek Z.
        • Paweletz N.
        Characteristic alterations of the peritoneum after carbon dioxide pneumoperitoneum.
        Surg Endosc. 1999; 13: 611-614https://doi.org/10.1007/s004649901052
        • Suematsu T.
        • Hirabayashi Y.
        • Shiraishi N.
        • Adachi Y.
        • Kitamura H.
        • Kitano S.
        Morphology of the murine peritoneum after pneumoperitoneum vs laparotomy.
        Surg Endosc. 2001; 15: 954-958https://doi.org/10.1007/s004640090100
        • Erikoglu M.
        • Yol S.
        • Avunduk M.C.
        • Erdemli E.
        • Can A.
        Electron-microscopic alterations of the peritoneum after both cold and heated carbon dioxide pneumoperitoneum.
        J Surg Res. 2005; 125: 73-77https://doi.org/10.1016/j.jss.2004.11.029
        • Peng Y.
        • Zheng M.
        • Ye Q.
        • Chen X.
        • Yu B.
        • Liu B.
        Heated and Humidified CO2 Prevents Hypothermia, Peritoneal Injury, and Intra-Abdominal Adhesions During Prolonged Laparoscopic Insufflations.
        J Surg Res. 2009; 151: 40-47https://doi.org/10.1016/j.jss.2008.03.039
        • Liu Y.
        • Hou Q.X.
        Effect of carbon dioxide pneumoperitoneum during laparoscopic surgery on morphology of peritoneum.
        Natl Med J China. 2006; 86
      1. Binda MM, Molinas CR, Mailova K, Koninckx PR. Effect of temperature upon adhesion formation in a laparoscopic mouse model. Hum Reprod 2004;19. https://doi.org/10.1093/humrep/deh495.

        • Molinas C.R.
        • Koninckx P.R.
        Hypoxaemia induced by CO2 or helium pneumoperitoneum is a co-factor in adhesion formation in rabbits.
        Hum Reprod. 2000; 15https://doi.org/10.1093/humrep/15.8.1758
        • Molinas C.R.
        • Campo R.
        • Dewerchin M.
        • Eriksson U.
        • Carmeliet P.
        • Koninckx P.R.
        Role of vascular endothelial growth factor and placental growth factor in basal adhesion formation and in carbon dioxide pneumoperitoneum-enhanced adhesion formation after laparoscopic surgery in transgenic mice.
        Fertil Steril. 2003; 80: 803-811https://doi.org/10.1016/S0015-0282(03)00768-4
        • Corona R.
        • Binda M.M.
        • Adamyan L.
        • Gomel V.
        • Koninckx P.R.
        N2O strongly prevents adhesion formation and postoperative pain in open surgery through a drug-like effect.
        Gynecol Surg. 2017; 14https://doi.org/10.1186/s10397-017-1024-2
        • Rosário M.T.A.
        • Ribeiro U.
        • Corbett C.E.P.
        • Ozaki A.C.
        • Bresciani C.C.
        • Zilberstein B.
        • et al.
        Does CO2 Pneumoperitoneum Alter the Ultra-Structuture of the Mesothelium?.
        J Surg Res. 2006; 133: 84-88https://doi.org/10.1016/j.jss.2005.09.032
        • Hazebroek E.J.
        • Schreve M.A.
        • Visser P.
        • de Bruin R.W.F.
        • Marquet R.L.
        • Bonjer H.J.
        Impact of temperature and humidity of carbon dioxide pneumoperitoneum on body temperature and peritoneal morphology.
        J Laparoendosc Adv Surg Tech - Part A. 2002; 12: 355-364https://doi.org/10.1089/109264202320884108
        • Armitage P.
        • Berry G.
        Factorial designs. Statistical methods in medical research.
        Blackwell Scientific Publications, Oxford, UK1987
        • Corona R.
        • Binda M.M.
        • Mailova K.
        • Verguts J.
        • Koninckx P.R.
        Addition of nitrous oxide to the carbon dioxide pneumoperitoneum strongly decreases adhesion formation and the dose-dependent adhesiogenic effect of blood in a laparoscopic mouse model.
        Fertil Steril. 2013; 100: 1777-1783https://doi.org/10.1016/j.fertnstert.2013.08.049
        • Francis I.P.
        • Islam E.A.
        • Gower A.C.
        • Shaik-Dasthagirisaheb Y.B.
        • Gray-Owen S.D.
        • Wetzler L.M.
        Murine host response to Neisseria gonorrhoeae upper genital tract infection reveals a common transcriptional signature, plus distinct inflammatory responses that vary between reproductive cycle phases.
        BMC Genomics. 2018; 19https://doi.org/10.1186/s12864-018-5000-7
        • Fuentes N.
        • Roy A.
        • Mishra V.
        • Cabello N.
        • Silveyra P.
        Sex-specific microRNA expression networks in an acute mouse model of ozone-induced lung inflammation.
        Biol Sex Differ. 2018; 9https://doi.org/10.1186/s13293-018-0177-7
        • Fuentes N.
        • Cabello N.
        • Nicoleau M.
        • Chroneos Z.C.
        • Silveyra P.
        Modulation of the lung inflammatory response to ozone by the estrous cycle.
        Physiol Rep. 2019; 7: e14026https://doi.org/10.14814/phy2.1402610.21203/rs.2.15141/v1