Dataset Information

Prevention of adhesions post-abdominal surgery: Assessing the safety and efficacy of Chitogel with Deferiprone in a rat model.

ABSTRACT:

Introduction

Adhesions are often considered to be an inevitable consequence of abdominal and pelvic surgery, jeopardizing the medium and long-term success of these procedures. Numerous strategies have been tested to reduce adhesion formation, however, to date, no surgical or medical therapeutic approaches have been successful in its prevention. This study demonstrates the safety and efficacy of Chitogel with Deferiprone and/or antibacterial Gallium Protoporphyrin in different concentrations in preventing adhesion formation after abdominal surgery.

Materials and methods

112 adult (8-10 week old) male Wistar albino rats were subjected to midline laparotomy and caecal abrasion, with 48 rats having an additional enterotomy and suturing. Kaolin (0.005g/ml) was applied to further accelerate adhesion formation. The abrasion model rats were randomized to receive saline, Chitogel, or Chitogel plus Deferiprone (5, 10 or 20 mM), together with Gallium Protoporphyrin (250?g/mL). The abrasion with enterotomy rats were randomised to receive saline, Chitogel or Chitogel with Deferiprone (1 or 5 mM). At day 21, rats were euthanised, and adhesions graded macroscopically and microscopically; the tensile strength of the repaired caecum was determined by an investigator blinded to the treatment groups.

Results

Chitogel with Deferiprone 5 mM significantly reduced adhesion formation (p<0.01) when pathologically assessed in a rat abrasion model. Chitogel with Deferiprone 5 mM and 1 mM also significantly reduced adhesions (p<0.05) after abrasion with enterotomy. Def-Chitogel 1mM treatment did not weaken the enterotomy site with treated sites having significantly better tensile strength compared to control saline treated enterotomy rats.

Conclusions

Chitogel with Deferiprone 1 mM constitutes an effective preventative anti-adhesion barrier after abdominal surgery in a rat model. Moreover, this therapeutic combination of agents is safe and does not weaken the healing of the sutured enterotomy site.

SUBMITTER: Vediappan RS

PROVIDER: S-EPMC7808615 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Publications

Prevention of adhesions post-abdominal surgery: Assessing the safety and efficacy of Chitogel with Deferiprone in a rat model.

Vediappan Rajan Sundaresan RS Bennett Catherine C Cooksley Clare C Finnie John J Trochsler Markus M Quarrington Ryan D RD Jones Claire F CF Bassiouni Ahmed A Moratti Stephen S Psaltis Alkis J AJ Maddern Guy G Vreugde Sarah S Wormald P J PJ

PloS one 20210114 1

<h4>Introduction</h4>Adhesions are often considered to be an inevitable consequence of abdominal and pelvic surgery, jeopardizing the medium and long-term success of these procedures. Numerous strategies have been tested to reduce adhesion formation, however, to date, no surgical or medical therapeutic approaches have been successful in its prevention. This study demonstrates the safety and efficacy of Chitogel with Deferiprone and/or antibacterial Gallium Protoporphyrin in different concentrati ...[more]

PMID: 33444337

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Project description:PurposeFibrin 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 materialsFemale 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.ResultsAnimals 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.ConclusionsThese findings indicate that selected fucoidans infused intraperitoneally for a week after abdominal operations reduce adhesion extent by up to 90%.

Project description:ObjectiveTo estimate the disease burden of the most important complications of postoperative abdominal adhesions: small bowel obstruction, difficulties at reoperation, infertility, and chronic pain.DesignSystematic review and meta-analyses.Data sourcesSearches of PubMed, Embase, and Central, from January 1990 to December 2012, without restrictions to publication status or language.Study selectionAll types of studies reporting on the incidence of adhesion related complications were considered.Data extraction and analysisThe primary outcome was the incidence of adhesive small bowel obstruction in patients with a history of abdominal surgery. Secondary outcomes were the incidence of small bowel obstruction by any cause, difference in operative time, enterotomy during adhesiolysis, and pregnancy rate after abdominal surgery. Subgroup and sensitivity analyses were done to study the robustness of the results. A random effects model was used to account for heterogeneity between studies.ResultsWe identified 196 eligible papers. Heterogeneity was considerable for almost all meta-analyses. The origin of heterogeneity could not be explained by study design, study quality, publication date, anatomical site of operation, or operative technique. The incidence of small bowel obstruction by any cause after abdominal surgery was 9% (95% confidence interval 7% to 10%; I(2)=99%). the incidence of adhesive small bowel obstruction was 2% (2% to 3%; I(2)=93%); presence of adhesions was generally confirmed by emergent reoperation. In patients with a known cause of small bowel obstruction, adhesions were the single most common cause (56%, 49% to 64%; I(2)=96%). Operative time was prolonged by 15 minutes (95% confidence interval 9.3 to 21.1 minutes; I(2)=85%) in patients with previous surgery. Use of adhesiolysis resulted in a 6% (4% to 8%; I(2)=89%) incidence of iatrogenic bowel injury. The pregnancy rate after colorectal surgery in patients with inflammatory bowel disease was 50% (37% to 63%; I(2)=94%), which was significantly lower than the pregnancy rate in medically treated patients (82%, 70% to 94%; I(2)=97%).ConclusionsThis review provides detailed and systematically analysed knowledge of the disease burden of adhesions. Complications of postoperative adhesion formation are frequent, have a large negative effect on patients' health, and increase workload in clinical practice. The quantitative effects should be interpreted with caution owing to large heterogeneity.RegistrationThe review protocol was registered through PROSPERO (CRD42012003180).

Dataset Information

Prevention of adhesions post-abdominal surgery: Assessing the safety and efficacy of Chitogel with Deferiprone in a rat model.

Introduction

Materials and methods

Results

Conclusions

Publications

Prevention of adhesions post-abdominal surgery: Assessing the safety and efficacy of Chitogel with Deferiprone in a rat model.

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