Carbon dioxide pneumoperitoneum prevents mortality from sepsis.

BACKGROUND: Carbon dioxide (CO2) pneumoperitoneum has been shown to attenuate the inflammatory response after laparoscopy. This study tested the hypothesis that abdominal insufflation with CO2 improves survival in an animal model of sepsis and investigated the associated mechanism. METHODS: The effect of CO2, helium, and air pneumoperitoneum on mortality was studied by inducing sepsis in 143 rats via intravenous injection of lipopolysaccharide (LPS). To test the protective effect of CO2 in the setting of a laparotomy, an additional 65 animals were subjected to CO2 pneumoperitoneum, helium pneumoperitoneum, or the control condition after laparotomy and intraperitoneal LPS injection. The mechanism of CO2 protection was investigated in another 84 animals. Statistical significance was determined via Kaplan-Meier analysis for survival and analysis of variance (ANOVA) for serum cytokines. RESULTS: Among rats with LPS-induced sepsis, CO2 pneumoperitoneum increased survival to 78%, as compared with using helium pneumoperitoneum (52%; p < 0.05), air pneumoperitoneum (55%; p = 0.09), anesthesia control (50%; p < 0.05), and LPS-only control (42%; p < 0.01). Carbon dioxide insufflation also significantly increased survival over the control condition (85% vs 25%; p < 0.05) among laparotomized septic animals, whereas helium insufflation did not (65% survival). Carbon dioxide insufflation increased plasma interleukin-10 (IL-10) levels by 35% compared with helium pneumoperitoneum (p < 0.05), and by 34% compared with anesthesia control (p < 0.05) 90 min after LPS stimulation. Carbon dioxide pneumoperitoneum resulted in a threefold reduction in tumor necrosis factor-alpha (TNF-alpha) compared with helium pneumoperitoneum (p < 0.05), and a sixfold reduction with anesthesia control (p < 0.001). CONCLUSION: Abdominal insufflation with CO2, but not helium or air, significantly reduces mortality among animals with LPS-induced sepsis. Furthermore, CO2 pneumoperitoneum rescues animals from abdominal sepsis after a laparotomy. Because IL-10 is known to downregulate TNF-alpha, the increase in IL-10 and the decrease in TNF-alpha found among the CO2-insufflated animals in our study provide evidence for a mechanism whereby CO2 pneumoperitoneum reduces mortality via IL-10-mediated downregulation of TNF-alpha.

Laparoscopic surgery and the parasympathetic nervous system.

BACKGROUND: Laparoscopic surgery preserves the immune system and has anti-inflammatory properties. CO2 pneumoperitoneum attenuates lipopolysaccharide (LPS)-induced cytokine production and increases survival. We tested the hypothesis that CO2 pneumoperitoneum mediates its immunomodulatory properties via stimulation of the cholinergic pathway. METHODS: In the first experiment, rats (n = 68) received atropine 1 mg/kg or saline injection 10 min prior to LPS injection and were randomization into four 30-min treatment subgroups: LPS only control, anesthesia control, CO2 pneumoperitoneum, and helium pneumoperitoneum. In a second experiment, rats (n = 40) received atropine 2 mg/kg or saline 10 min prior to randomization into the same four subgroups described previously. In a third experiment, rats (n = 96) received atropine 2 mg/kg or saline 10 min prior to randomization into eight 30-min treatment subgroups followed by LPS injection: LPS only control; anesthesia control; and CO2 or helium pneumoperitoneum at 4, 8, and 12 mmHg. In a fourth experiment, rats (n = 58) were subjected to bilateral subdiaphragmatic truncal vagotomy or sham operation. Two weeks postoperatively, animals were randomized into four 30-min treatment subgroups followed by LPS injection: LPS only control, anesthesia control, CO2 pneumoperitoneum, and helium pneumoperitoneum. Blood samples were collected from all animals 1.5 h after LPS injection, and cytokine levels were determined by enzyme-linked immunosorbent assay. RESULTS: Serum tumor necrosis factor-alpha (TNF-alpha) levels were consistently suppressed among the saline-CO2 pneumoperitoneum groups compared to saline-LPS only control groups (p < 0.05 for all four experiments). All chemically vagotomized animals had significantly reduced TNF-alpha levels compared to their saline-treated counterparts (p < 0.05 for all), except among the CO2 pneumoperitoneum-treated animals. Increasing insufflation pressure with helium eliminated differences (p < 0.05) in TNF-alpha production between saline- and atropine-treated groups but had no effect among CO2 pneumoperitoneum-treated animals. Finally, vagotomy (whether chemical or surgical) independently decreased LPS-stimulated TNF-alpha production in all four experiments. CONCLUSION: CO2 pneumoperitoneum modulates the immune system independent of the vagus nerve and the cholinergic pathway.

A comprehensive review of anti-reflux procedures completed by computer-assisted tele-surgery.

Gastro-esophageal reflux disease (GERD) is the most common esophageal disorder. Although GERD is an illness primarily treated by medical management, patients refractory to, or those unwilling to endure long-term medical therapy often undergo anti-reflux surgery. Laparoscopic surgery made the surgeon's task technically more challenging. While laparoscopy provides a good field of vision, all depth perception is lost. Furthermore, the movements of the chopstick-like instruments are counter-intuitive with limited degrees of freedom, diminished tactile feedback, and disassociated movement. Now that advanced minimally invasive surgeons have acquired the necessary skills to overcome these hurdles, technology has developed a way to make laparoscopic surgery easier. The latest advance in laparoscopic surgery is computer-assisted telesurgery (CATS) which allows the surgeon to be seamlessly submerged into the surgical field while being seated at a distance from the patient. The technological advances afforded by CATS make minimally-invasive surgery easier by adding stereoscopic vision, which provides depth perception, and the endo-wrist, which provides wrist-like dexterity within the abdominal cavity. The advantages of CATS are: the ergonomic positioning of the surgeon thus decreasing fatigue; stereoscopic vision with possibility of 10x magnification; wrist-like manual dexterity with intuitive motion; motion-scaling and tremor elimination all of which enhance precision and accuracy. A small yet growing body of evidence has provided information which suggests that the use of CATS for anti-reflux surgery is equivalent to the current gold standard, unassisted laparoscopy.

Expression, activity and cellular localization of inducible nitric oxide synthase in rat ileum and colon post-irradiation.

PURPOSE: Studies were conducted to determine the acute effect of exposure to ionizing radiation on inducible nitric oxide synthase (iNOS) activity and expression in the rat ileum and colon. MATERIALS AND METHODS: Rats received whole body exposure to 10 Gy gamma-radiation and were studied 0.5-48 h later. Segments of ileum and colon were taken from anaesthetized rats for determination of myeloperoxidase activity (a marker of acute inflammation), and iNOS mRNA expression, enzyme activity and localization. RESULTS: Myeloperoxidase activity in ileum was not increased compared with shams until 48 h post-irradiation. In colon, myeloperoxidase activity was lower than shams at 48 h post-irradiation. Irradiation resulted in a dexamethasone-sensitive expression of iNOS mRNA in both the ileum and colon within 2h. Inducible NOS activity was significantly elevated in the ileum, but not in the colon. The elevated ileal nitric oxide synthase activity was significantly reduced by pretreatment with the iNOS inhibitor, aminoguanidine. Immunoreactivity for iNOS protein was localized to the epithelium and was apparent at 2-6 h post-irradiation in the ileum, but not the colon. CONCLUSIONS: Exposure to ionizing radiation results in the expression of iNOS in ileum and colon, but only significantly increases iNOS activity in the ileum. Inducible NOS-derived NO may participate in acute, whole body radiation-induced ileal dysfunction, independently of the development of an inflammatory response.