title: The influence of the CO₂ pneumoperitoneum on a rat model of intestinal anastomosis healing.
abstract: BACKGROUND
  The CO(2) pneumoperitoneum, which is used for laparoscopic surgery, causes local and systemic effects in patients. Concern arises about what the pressurized anoxic environment of the CO(2) pneumoperitoneum has on intestinal healing. Earlier experimental work showed a negative correlation between intestinal healing and the applied intra-abdominal pressure. To further elucidate this, we developed a rat model, in which enterotomy healing can be compared after open or laparoscopic surgery. Possible mechanisms of injury, such as impaired neoangiogenesis or injury through hypoxia-induced pathways were studied.
  
  
  METHODS
  A new experimental mechanically ventilated rat model was developed. An enterotomy was made and closed via laparotomy (group I) or laparoscopy under CO(2) pressures of 5 mmHg (group II) or 10 mmHg (group III). Intestinal healing was tested in vivo after 1 week by bursting-pressure analysis. The effect of the operative procedure on neoangiogenesis was tested by counting factor VIII positive vessels in biopsies of the perianastomotic granulation tissue after 1 week. Intestinal anoxia was tested by quantifying HIF-1α protein levels in intestinal biopsies, taken before the enterotomy closure.
  
  
  RESULTS
  The bursting pressures were significantly lower after laparoscopic surgery at 10 mmHg CO(2) pneumoperitoneum (group III) compared with rats that had undergone open surgery (group I) or laparoscopic surgery at 5 mmHg CO(2) pneumoperitoneum (group II). There was no significant quantitative difference between the three groups in the neoangiogenesis nor was there a difference in the amount of HIF-1α measured in the intestinal biopsies.
  
  
  CONCLUSIONS
  We developed a surgical model that is well fitted to study the effects of pneumoperitoneum on intestinal healing. With this model, we found further evidence of CO(2) pressure-dependant hampered intestinal healing. These differences could not be explained by difference in neoangiogenesis nor local upregulation of hypoxic factors.
authors.affiliation: Department of Pediatric Surgery, Wilhelmina Children's Hospital, University Medical Center Utrecht, KE.04.140.5, PO Box 85090, 3508, AB Utrecht, The Netherlands. s.tytgat@umcutrecht.nl
authors.forename: Stefaan H A J
authors.initials: SH
authors.lastname: Tytgat
authors.forename: Ger T
authors.initials: GT
authors.lastname: Rijkers
authors.forename: David C
authors.initials: DC
authors.lastname: van der Zee
mesh_terms: D000714:Anastomosis, Surgical / Q000379:methods; D000818:Animals; D001835:Body Weight; D002245:Carbon Dioxide / Q000009:adverse effects*; D002432:Cecum / Q000098:blood supply / Q000601:surgery*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D007082:Ileum / Q000098:blood supply / Q000601:surgery*; D007118:Immunoassay; D007511:Ischemia / Q000209:etiology; D010535:Laparoscopy / Q000009:adverse effects*; D008297:Male; D023421:Models, Animal; D018919:Neovascularization, Physiologic; D011028:Pneumoperitoneum, Artificial / Q000009:adverse effects*; D011312:Pressure; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D014945:Wound Healing / Q000502:physiology*
chemical_list: C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D002245:Carbon Dioxide