S. K. Hyoju1, S. Morrison1, M. Gharedaghi1, M. Mohamed1, S. S. Gul1, M. Najibi1, T. Phupitakphol1, A. Osmani1, K. Economopoulos1, S. Hamarneh1, R. A. Hodin1 1Massachusetts General Hospital,Department Of Surgery,Boston, MA, USA
Introduction: Damage to the peritoneum initiates an inflammatory response leading to the formation of adhesions which subsequently cause significant morbidity in some patients. Intestinal alkaline phosphatase (IAP) is a gut enzyme capable of detoxifying various inflammatory mediators such as lipopolysaccharide, lipoteichoic acid, CpG DNA and nucleotide triphosphates, and could therefore play a role in decreasing adhesion formation. This study aimed to test the anti-inflammatory effects of IAP on the development of post-operative adhesions in mice.
Methods: C57BL/6 mice were used in this study and underwent midline laparotomy. Six peritoneal buttons were created by pinching and ligating the peritoneum with 5-0 silk sutures. The buttons were subsequently cut and cauterized. The cecum was exteriorized and abraded with sterile dry gauze and returned to the abdominal cavity. At designated time points during the procedure, a total of, 500µl of either IAP (5000U) or vehicle was applied over the peritoneal cavity. On the 21st postoperative day, mice were euthanized and adhesions from abdominal viscera to each button were scored based on number, tenacity, and extent of the adhesions. The final adhesion score for each mouse was calculated by the summation of these scores. The investigators were blinded to the treatment groups. In a second series of experiments, this procedure was repeated, and the animals were instead euthanized on the 1st post operative day. Peritoneal buttons were then excised and homogenized, and the resulting supernatant was collected for cytokine analysis.Student’s t test was used to analyze the data
Results:The mice treated with IAP had significantly lower adhesion scores compared to vehicle-treated animals (16.4 ± 6.8 vs. 27.8 ± 8.7, P = 0.04).Peritoneal button homogenates from IAP-treated mice had significantly lower IL-1β level and TNF-α levels compared to vehicle-treated animals (64.57±7.4 vs. 111.31±18.9 pg/mg tissue protein, P=0.0006; 6.76±1.69 vs. 10.5±3.07 pg/mg tissue protein, P=0.04) respectively.
Conclusion:Intraperitoneal application of IAP at the time of laparotomy could represent a novel approach to the prevention of post-operative adhesions.
