The Journal of Thoracic and Cardiovascular Surgery
Volume 135, Issue 4 , Pages 777-783, April 2008

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

  • Juan Zhou, MD, PhD

      Affiliations

    • Department of Surgery, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia
  • ,
  • Robert S. Liwski, MD, PhD

      Affiliations

    • Department of Pathology, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia
  • ,
  • Clive Elson, PhD

      Affiliations

    • Department of Chemistry, Saint Mary's University, Halifax, Nova Scotia
  • ,
  • Timothy D.G. Lee, PhD

      Affiliations

    • Department of Surgery, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia
    • Department of Pathology, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia
    • Corresponding Author InformationAddress for reprints: Tim Lee, PhD, Sir Charles Tupper Building, 5850 College Street, Dalhousie University, Halifax, NS, Canada, B3H 4H7.

Received 18 January 2007; received in revised form 23 August 2007; accepted 19 September 2007.

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 3H-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 3H-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.

Abbreviations and Acronyms: dpm, disintegrations per minute, FCS, fetal calf serum, HA, hyaluronic acid, NOCC, N,O-carboxymethyl chitosan, sfRPMI, serum-free Roswell Park Memorial Institute [medium]

CTSNet classification: 18, 25

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 This work was supported in full by Kytogenics Pharmaceuticals Ltd. Dr Elson reports consulting fees, equity ownership, and employment by Kytogenics Pharma Ltd, the manufacturer of the gel described in this report. Drs Zhou, Liwski, and Lee have no financial interest in Kytogenics Ltd.

PII: S0022-5223(07)01638-8

doi:10.1016/j.jtcvs.2007.09.033

The Journal of Thoracic and Cardiovascular Surgery
Volume 135, Issue 4 , Pages 777-783, April 2008