Reduction in postsurgical adhesion formation after cardiac surgery in a rabbit model using N,O-carboxymethyl chitosan to block cell adherence.

OBJECTIVE: The study objectives were to (1) assess the efficacy of N,O-carboxymethyl chitosan on postsurgical adhesion formation after cardiac surgery using a rabbit cardiac injury model and (2) explore the mechanism of action of N,O-carboxymethyl chitosan in the prevention of postsurgical adhesions using in vitro experimentation. METHODS: In the rabbit cardiac injury model, cardiac injury was generated by abrading the anterior surface of the heart with gauze and desiccated with oxygen. The rabbits were then either treated with N,O-carboxymethyl chitosan gel and solution on the injured surface or not treated. Fourteen days or 3 months after surgery, the severity and area of adhesion between the heart and sternum were evaluated. In the in vitro adherence assay, murine fibroblasts and macrophages were labeled with (3)H-thymidine and added to sterile tissue culture plates that had been precoated with N,O-carboxymethyl chitosan solution, culture medium, or hyaluronic acid. After incubation, the cells adherent to the coated plates were harvested and the levels of (3)H-thymidine were measured. RESULTS: Animals treated with N,O-carboxymethyl chitosan gel and solution showed significantly (P < .01) reduced severity and area of adhesion formation. Murine fibroblasts and macrophages did not adhere to N,O-carboxymethyl chitosan-coated tissue culture plates, even in the presence of serum. CONCLUSION: The application of N,O-carboxymethyl chitosan gel and solution significantly reduces the severity of postsurgical adhesion formation after cardiac surgery in the rabbit model. The inability of fibroblasts to adhere to N,O-carboxymethyl chitosan-coated surfaces suggests that N,O-carboxymethyl chitosan may act as a biophysical barrier.

Use of a sulfated chitosan derivative to reduce bladder inflammation in the rat.

OBJECTIVES: Interstitial cystitis is a chronic, debilitating disease of the bladder. Treatments using intravesicular inoculation of long-chain polysaccharide formulations, such as hyaluronic acid or anti-inflammatory agents, have been used to some effect. The objective of this study was to test a long-chain polysaccharide derivative of chitosan as a vehicle for delivery of the anti-inflammatory agent 5-aminosalicylic acid (5-ASA) for treatment of inflammation in the bladder. METHODS: Bladder inflammation was induced in rats by intravesicular inoculation of protamine sulfate and lipopolysaccharide. Groups of rats were randomly assigned to the treated or control groups, which received either the treatment agents or saline 24 hours after induction. The animals were killed 5 days after inoculation, and the bladders harvested for histologic examination of inflammation by a blinded observer. Four parameters of inflammation were measured using a 6-point scale. In another experiment, urinary frequency was measured 4 days after inoculation. RESULTS: The most potent treatment agent was 3% N-sulphonato-N,O-carboxymethylchitosan plus 5-ASA, with a mean reduction in inflammation, as measured by histologic examination, of up to 75%. This level of reduction was significantly greater than that seen by treatment with the commercially available product Cystistat. In a separate experiment, 3% N-sulphonato-N,O-carboxymethylchitosan plus 5-ASA ameliorated the increase in urinary frequency seen in induced, untreated animals. CONCLUSIONS: The combination of 3% N-sulphonato-N,O-carboxymethylchitosan and 5-ASA reduced bladder inflammation as measured by histologic examination and by the lower urinary frequency.

Reduction in postoperative adhesion formation and re-formation after an abdominal operation with the use of N, O - carboxymethyl chitosan.

BACKGROUND: Postoperative adhesions have proven to be intractable complications after abdominal operations. This study assessed the efficacy of N, O - carboxymethyl chitosan (NOCC) to limit adhesion formation and re-formation in a rabbit abdominal surgery model. METHODS: In study 1 (adhesion formation), injuries to the large bowel, cecum, and abdominal sidewall were generated in rabbits. The rabbits (10/group) were randomly assigned to 1 of 5 treatment groups: Group A received no NOCC treatment; in group B, NOCC gel was applied directly to the injured site and NOCC solution was applied throughout the abdominal cavity; in group C, NOCC gel was applied near the injured site and NOCC solution was applied as above; in group D, NOCC gel was applied distant to the injury and NOCC solution was applied as above; in group E, a mixture of NOCC gel and solution was applied at the injured site. Adhesions were evaluated 14 days later. In study 2 (adhesion re-formation), adhesions were generated as above but were then lysed by careful dissection. After adhesiolysis, the rabbits (9/group) were treated with NOCC gel and solution at the site of adhesiolysis or left untreated. Adhesion re-formation was assessed 14 days later. In study 3 (mechanism of action), sterile tissue culture plates were coated with NOCC and adhesion of cultured, radiolabeled murine fibroblasts to the plates was assessed. RESULTS: In study 1, animals treated with NOCC gel and solution showed reduced adhesion formation (P<.01). NOCC gel was equally efficacious if applied on the site of injury or near the site of injury but less efficacious if applied at a site distant to the injury. In study 2, animals treated with NOCC gel and solution showed less adhesion re-formation compared with the untreated control animals (P<.01). In study 3, murine fibroblasts did not adhere to NOCC-coated tissue culture plates. CONCLUSIONS: NOCC gel and solution can reduce adhesion formation and re-formation in this rabbit model. The inability of fibroblasts to adhere to NOCC solution-coated surfaces suggests that NOCC may act as a biophysical barrier.