Purpose Fibrin clot is essential for post-operative abdominal adhesion formation. Fucoidans, sulfated polysaccharides, inhibit fibrin clot formation. In addition, they inhibit inflammation and fibrosis, which also play important roles in adhesion formation. The purpose of this study was to evaluate fucoidans’ potential for inhibiting post-operative abdominal adhesions and measure their effects on systemic coagulation parameters when administered intraperitoneally (IP). Methods and materials Female Sprague Dawley rats were studied. A 2.5x2.5cm full thickness segment of abdominal wall was excised. The skin edges were approximated. This model induces extensive adhesions and allows objective quantitation. Three fucoidans were evaluated- Sigma Fucoidan Crude (SFC), Fucus vesiculosis 95% (Sigma) and, Peridan. One protocol involved continuous infusion into the abdomen from a subcutaneous osmotic pump. Alternatively, boluses of the solutions were injected IP at the end of the operation. Rats were sacrificed a week later. Adhesion extent was scored. Systemic coagulation effects of fucoidans were also evaluated. INR and aPTT were measured following IP injection of the fucoidan solutions and after 7 days of continuous infusion. Results Animals given a continuous infusion of either SFC or Peridan yielded adhesion reduction of 80 to 90% from control. Bolus Peridan had no discernable influence on adhesion formation, but a single bolus of SFC caused significant adhesion reductions. Peridan resulted in prompt aPTT elevations which fell to nearly normal by 5 hours. The maximum peak value after SFC injection was seen in 15 hours. The maximal INR elevations were around 2. Measurement of INR and aPTT after a week of continuous infusion of either Peridan or SFC, were always in the normal control range. The third agent, Sigma, frequently yielded intraperitoneal infection found at autopsy. Conclusions These findings indicate that selected fucoidans infused intraperitoneally for a week after abdominal operations reduce adhesion extent by up to 90%.
Bibliographical noteFunding Information:
Competing interest statement: This work was supported by private investment of G.D.N. Holdings and Anhese, LLC. Author J.P.D. was a board member of Anhese, LLC at the time of these experiments. However, no authors received direct payment from either company. Dr. Delaney did participate in manuscript preparation, experimental design, and the decision to publish. Anhese, LLC applied for and held a provisional patent for the use of fucoidans for adhesion prevention, but the provisional patent has since lapsed. Anhese, LLC has since dissolved. G.D.N. Holdings did not have any role in experimental design, data collection, or preparation of this manuscript. There is currently no financial stake in the outcome of this manuscript or the use of fucoidans for adhesion prevention for the authors of this manuscript or the companies that funded the work. This does not alter our adherence to PLOS ONE policies on sharing data and materials.
This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.