Özet:
The aim of this study was to investigate in rats
whether preoperative orogastric administration of low
doses of cholera toxin would influence the mechanical
strength of experimental colonic anastomosis on the basis
of the gut mucosal immunomodulation effect of this antigen.
METHODS: The cholera toxin group (n 14) was fed
10 g of cholera toxin in phosphate-buffered saline three
times before surgery at 10-day intervals, whereas the controls
(n 14) received phosphate-buffered saline only.
Twenty-four hours after the last dose of cholera toxin (or
placebo in control group), the animals underwent left colonic
transection and anastomosis. Seven days after colonic
transection-anastomosis, the bursting pressure of the anastomotic
segment was recorded in situ. Perianastomotic and
extra-anastomotic tissue samples were obtained for measurements
of tissue transforming growth factor-beta, interleukin-6,
and interferon-gamma levels with enzyme-linked
immunosorbent assay. RESULTS: Cholera toxin administration
resulted in a significantly higher bursting pressure than
in the control group (165.78 12.37 vs. 138.4 7.87
mmHg; P 0.001). Compared with the control group, the
heightened mechanical strength of colonic anastomosis
provided by cholera toxin was associated with significant
increases in the perianastomotic tissue levels of transforming
growth factor-beta (199.34 24.85 vs. 70.66 10.63
pg/ml; P 0.001) and interleukin-6 (439.31 95.14 vs.
289.57 96.59 pg/ml; P 0.001), whereas interferongamma
was significantly lower (174.04 44.82 vs. 219.00
31.35 pg/ml; P 0.05). This cytokine pattern induced by
cholera toxin in the wound milieu was also found to be
similar in the extra-anastomotic colon. CONCLUSION: The
mechanical strength of uncomplicated experimental colonic
anastomosis increased significantly with gut mucosal immunomodulation
with repeated low preoperative doses of cholera
toxin. This enhanced healing had significant positive correlation
with the colonic tissue level of transforming growth factor-beta
and inverse correlation with interferon-gamma. If the
relevant dose regimen is identified and its safety is assured in
humans, gut mucosal immunomodulation might provide an
efficient, safe, and inexpensive tool to improve surgical outcome
in colorectal surgery, particularly in high-risk situations.
