ATIII attenuates endotoxemia induced healing impairment in the colon.

Diller R, Stratmann U, Minin E, von Eiff C, Bäumer G, Huismans H, Helmschmied T, Becker K, Spiegel HU

Abstract

BACKGROUND: Intra-abdominal infections are considered a contributing factor to the impairment of anastomotic healing in patients undergoing surgical procedures of digestive system. Antithrombin (ATIII) is known to improve the microcirculation in sepsis. We hypothesized that it may also positively influence the healing of the colon anastomoses under endotoxemia. MATERIALS AND METHODS: Ninety Balb/c mice (n = 10 per group on day 2, 4, and 7) were randomly assigned to three groups: Control (N), Sepsis (S) (administration of lipopolysaccharides (LPS) dosed at 2 mg/kg bodyweight, 18 h before colon surgery), and Sepsis with ATIII therapy (SIII) (administration of LPS and ATIII). All the animals underwent colonic anastomoses. Immediately after their completion, microcirculatory parameters were measured, and both macroscopic and histological parameters were assessed on day 2, 4, and 7 postoperation. Additionally, immunohistology studies were performed for CD31, ssDNA, and iNOS, along with an examination for bacterial translocation to the mesenteric lymph nodes. RESULTS: Compared with group S, the functional capillary network was denser in the control group N (P < 0.001) and group SIII (P < 0.01). Mean bursting pressures were significantly lower in group S compared with group N, on day 2, 4, and 7, and with group SIII on day 2 and 7. At the anastomosis, the inflammatory infiltrate in group S was denser compared with groups N (P < 0.001) and SIII (P < 0.01). Furthermore, the apoptotic rate was higher, and the vascular density was lower on day 7 in group S compared with groups SIII and N (P < 0.05). Bacterial translocation decreased over time (P < 0.05) with no significant differences between the groups. CONCLUSION: ATIII improved the anastomotic microcirculatory parameters and anastomotic healing in mice with endotoxemia, though the improvement failed to achieve the levels of the control mice.