Inflammation and neutrophil recruitment in healing of colonic anastomosis
Research output: Thesis › Doctoral Thesis (compilation)
Wound healing is a multistep process with an initial inflammatory response, followed by synthesis of extracellular matrix components and finalized by a repair phase. One main goal was to determine the impact and adhesive mechanisms of neutrophil recruitment in anastomotic healing in the colon. Passive immunization against CD18 abolished anastomotic accumulation of neutrophils, whereas no effect on breaking strength was observed. Another aim was to develop a new approach to study anastomotic repair and to compare it with mechanical methods, such as breaking strength and bursting pressure. By application of this radiological approach, it was observed that the integrity increased progressively after operation. No change in breaking strength was observed up to three days postoperatively, in contrast to anastomotic bursting pressure that increased progressively. Notably, integrity and bursting pressure increased in parallel to the accumulation of neutrophils in the anastomotic segment. Local irradiation, enhanced neutrophil influx but did not increase leakage, and administration of chemotherapy, decreased neutrophil influx but increased anastomotic leakage. Moreover, anastomotic leakage and mortality increased in rats with a diverting colostomy. By application of intravital microscopy, it was shown that a P-selectin antibody, but not a L-selectin antibody, abolished TNF-a-induced rolling and concomitantly caused a marked attenuation of firm adhesion and tissue accumulation of neutrophils. TNF-a production was markedly increased and inhibition of P-selectin abolished neutrophil recruitment in colonic anastomosis in animals with experimental colitis. However, this inhibition of P-selectin fraction and neutrophil accumulation had no effect on anastomotic leakage in the inflamed colon. In conclusion, this thesis presents a novel approach to study anastomotic repair in the rat colon by use of radiological examination of contrast media leakage. Moreover, breaking strength is not sensitive enough to detect early changes in anastomotic healing, whereas bursting pressure time-dependently increases up to three days after formation of colonic anastomosis. Finally, it is concluded that neutrophils do not exert a negative influence on the normal non-infected repair process of colonic anastomosis.
|Research areas and keywords||
Subject classification (UKÄ) – MANDATORY
|Award date||2001 Oct 10|
|Publication status||Published - 2001|
Defence details Date: 2001-10-10 Time: 10:15 Place: lecture room, Surg. Clinic Malmö External reviewer(s) Name: Sjödahl, Rune Title: Prof Affiliation: Linköping University, Sweden ---