The effect of carbon dioxide pneumoperitoneum on peritoneal oxidative stress and post-operative adhesion formation

Carbon dioxide (CO₂) is the standard gas used for abdominal insufflation during laparoscopy. Various studies have suggested that CO ₂-pneumoperitoneum attenuates the local inflammatory response, induces splanchnic microcirculatory changes, and alters the peritoneal oxidative status. We have previously demonstrated that the laparoscopic approach, when compared to laparotomy, significantly increased the peritoneal levels of 8-iso prostaglandin F_2α (8-iso PGF_2α), a marker of oxidative stress. The mechanisms by which CO₂-pneumoperitoneum induces oxidative stress are unclear, but can be related to the intra-abdominal pressure or to CO₂ itself.; In this dissertation, we hypothesized that both intra-abdominal pressure and carbon dioxide could induce oxidative stress in the peritoneum and this, in turn, would be associated with post-operative adhesion formation. In order to verify our hypotheses, we initially investigated the effect of intra-abdominal pressure on peritoneal oxidative status during laparoscopy in rabbits by using different pneumoperitoneum pressures and measuring 8-iso PGF_2α in the parietal peritoneum collected at various time points throughout the experiment. The impact of oxidative stress on the peritoneal healing process was estimated by assessing post-operative adhesion formation in a second-look laparoscopy performed 14 days after the initial procedure. In the second part of our study, we examined the effects of in vitro exposure to CO₂ on the levels of 8-iso PGF_2α in cultured human peritoneal mesothelial cells, measured at various time points after gas incubation. In the last section of our study, we verified the changes in proliferative and apoptotic profiles of human peritoneal mesothelial cells upon in vitro exposure to carbon dioxide.; We conclude that CO₂-pneumoperitoneum increases the levels of 8-iso PGF_2α in a time- and pressure-dependent manner, and the frequency and severity of post-operative adhesion formation in a pressure-dependent manner. No correlation, however, was found between concentration of 8-iso PGF_α, and adhesion score. In vitro exposure to CO₂ increases the levels of 8-iso PGF_2α in human peritoneal mesothelial cells in a time-dependent manner, and hypoxia-reoxygenation seems to be involved in the process. The increase of 8-iso PGF_2α may induce cell growth arrest as a decrease in cell proliferation was observed after exposure to carbon dioxide.; This study provides an important contribution to a better understanding of the pathophysiology of CO₂-pneumoperitoneum, and gives the background for further investigations that will help to improve surgical conditions and prevent unnecessary trauma.