Release of glutaraldehyde from an albumin-glutaraldehyde tissue adhesive causes significant in vitro and in vivo toxicity

Ann Thorac Surg. 2005 May;79(5):1522-8; discussion 1529. doi: 10.1016/j.athoracsur.2004.11.054.

Abstract

Background: A two-component sealant composed of bovine serum albumin and glutaraldehyde (BioGlue) is used to treat aortic dissections. Although glutaraldehyde guarantees strong adherence to tissues and synthetic materials, its toxic potential should be considered. The aim of this study was to determine the amount of glutaraldehyde released from BioGlue, its cytotoxic effects on cultured cells, and the local reaction of lung, liver, and aortic tissues to BioGlue.

Methods: BioGlue was prepared according to the product insert, allowed to polymerize, and then overlaid with saline solution. The supernatant was analyzed for its content of glutaraldehyde. The cytotoxic effect of BioGlue was evaluated by adding the supernatants to either cultured human embryo fibroblasts (MRC5) or mouse myoblasts (C2C12). In vivo toxicity was assessed on three different tissues by applying BioGlue onto a partial lung resection, a liver abrasion, or an intact abdominal aorta in rabbits. Tissue samples were histologically evaluated 2 and 7 days after application.

Results: Saline supernatants from polymerized BioGlue contained 100 to 200 mug/mL glutaraldehyde and were cytotoxic to both cell lines tested. Application of BioGlue to lung and liver tissue evoked serious adverse effects consisting of high-grade inflammation, edema, and toxic necrosis. Intact aortic tissue showed only low-grade or medium-grade inflammation.

Conclusions: Polymerized BioGlue releases amounts of glutaraldehyde that are capable of inducing cytotoxic effects both in vitro and in vivo. Use of BioGlue should be restricted to the aortic dissection procedure, as other tissues are sensitive to the amounts of glutaraldehyde released from the glue.

MeSH terms

  • Animals
  • Cell Line
  • Cell Survival / drug effects
  • Coloring Agents
  • Glutaral / analysis*
  • Glutaral / toxicity*
  • Humans
  • Inflammation / chemically induced
  • Liver / drug effects
  • Liver / pathology
  • Lung / drug effects
  • Lung / pathology
  • Mice
  • Models, Animal
  • Proteins / chemistry*
  • Rabbits
  • Serum Albumin / analysis
  • Tissue Adhesives / chemistry*

Substances

  • Bio-glue
  • Coloring Agents
  • Proteins
  • Serum Albumin
  • Tissue Adhesives
  • Glutaral