title: Chondroitinase ABC (pharmaceutical grade) for chemonucleolysis. Functional and structural evaluation after local application on intraspinal nerve structures and blood vessels.
abstract: METHODS
  The effects on nerve tissue and blood vessels of locally applied chondroitinase ABC were studied in two experimental models using chymopapain and the vehicle of chondroitinase ABC for controls.
  
  
  OBJECTIVE
  To assess the effects of chondroitinase ABC on blood vessels and nerve tissue after local application.
  
  
  BACKGROUND
  Chondroitinase ABC has been suggested for chemonucleolysis because it has a high specificity for nucleus pulposus matrix, which could mean a high efficiency in dissolving disc tissue combined with a low risk of side effects on other tissues.
  
  
  METHODS
  Chondroitinase ABC or controls were injected intrathecally in the pig, and nerve conduction velocity and histologic changes were assessed after 7 days. The same substances were injected into the hamster cheek pouch and studied for 60 minutes for microvascular effects. The vehicle for the enzyme was used as a negative control and chymopapain in a therapeutic concentration served as a positive control.
  
  
  RESULTS
  In all series there was a slight intrathecal fibrotic reaction that was most pronounced after chymopapain injection. The effects on nerve conduction velocity and nerve morphology were similar between chondroitinase ABC and its vehicle. Chymopapain induced a significant reduction in nerve conduction velocity and pronounced histologic changes. In the cheek pouch, chymopapain induced a stand-still of blood flow at the injection site, and microhemorrhage and macromolecular leakage from the vessels at the border of the injection site. Only a slightly reduced blood flow was occasionally found after injection of chondroitinase ABC and controls.
  
  
  CONCLUSIONS
  In agreement with the current literature, these observations indicate that chondroitinase ABC is safe regarding adverse effects on nerve tissue and blood vessels. The slight reduction in conduction velocity after intrathecal injection of chondroitinase ABC or its vehicle is most likely the result of surgical injury while releasing the nerve roots from the intrathecal fibrous adhesions. Such adhesions may be related to the laminectomy per se, and probably have no pathophysiologic significance.
authors.affiliation: Department of Orthopaedics, Sahlgren University Hospital, Gothenburg, Sweden, USA.
authors.forename: K
authors.initials: K
authors.lastname: Olmarker
authors.forename: J
authors.initials: J
authors.lastname: Strömberg
authors.forename: J
authors.initials: J
authors.lastname: Blomquist
authors.forename: P
authors.initials: P
authors.lastname: Zachrisson
authors.forename: U
authors.initials: U
authors.lastname: Nannmark
authors.forename: C
authors.initials: C
authors.lastname: Nordborg
authors.forename: B
authors.initials: B
authors.lastname: Rydevik
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000473:pathology; D002808:Chondroitin Lyases / Q000008:administration & dosage / Q000627:therapeutic use*; D002917:Chymopapain / Q000494:pharmacology; D006224:Cricetinae; D004824:Epidural Space; D006470:Hemorrhage / Q000139:chemically induced; D007278:Injections, Spinal; D007404:Intervertebral Disc Chemolysis; D008647:Mesocricetus; D009431:Neural Conduction; D013116:Spinal Cord / Q000473:pathology / Q000503:physiopathology*; D013118:Spinal Cord Diseases / Q000139:chemically induced; D013131:Spine / Q000098:blood supply*; D013552:Swine
chemical_list: D002917:Chymopapain; D002808:Chondroitin Lyases