title: Regional differences in the subacute response of rabbit orbicularis oculi to bupivacaine-induced myotoxicity as quantified with a neural cell adhesion molecule immunohistochemical marker.
abstract: OBJECTIVE
  This study examined the subacute myotoxic effects of injection of the local anesthetic bupivacaine on the orbicularis oculi muscle in the rabbit eyelid. In contrast to other muscles, the orbicularis oculi was resistant to injury by the usual anesthetic doses of bupivacaine when local infiltration is used. An attempt was made to assess the sensitivity of orbicularis oculi muscle to bupivacaine using a variety of increased bupivacaine concentrations and in combination with hyaluronidase.
  
  
  METHODS
  Bupivacaine was injected into rabbit lower eyelids at a variety of doses with and without the injection of hyaluronidase before bupivacaine treatment. Muscle injury was assessed immunohistochemically using an antibody to an isoform of neural cell adhesion molecule, anti-leu-19, a molecule shown to localize on the surface of regenerating muscle fibers. The number of neural cell adhesion molecule-positive muscle fibers was assessed 4 and 7 days after bupivacaine injection to determine the number of fibers that were injured.
  
  
  RESULTS
  When bupivacaine was injected into the lower eyelid at a dose of 1.5 mg, only 10% of the orbicularis oculi muscle was injured. The most effective injury involved either multiple injections of 3 mg bupivacaine or of hyaluronidase 20 minutes before the injection of 3 mg bupivacaine, resulting in injury of up to 58% of the muscle fibers. In all cases, the preseptal region of the orbicularis oculi showed a greater percentage of injury than the pretarsal portions of the muscle.
  
  
  CONCLUSIONS
  Although multiple injections of bupivacaine and bupivacaine combined with hyaluronidase significantly increased the percentage of muscle cells injured, total destruction of the orbicularis oculi muscle was never seen. Neural cell adhesion molecule was a good marker for the quantification of the regenerating muscle fibers. It is proposed that the tight fasciculation of the orbicularis oculi muscle may play a role in preventing access of the local anesthetic to the individual muscle fibers. This demonstrates the relative clinical safety of local anesthetic injection into the eyelid.
authors.affiliation: Department of Ophthalmology, University of Minnesota, Minneapolis 55455.
authors.forename: L K
authors.initials: LK
authors.lastname: McLoon
authors.forename: J
authors.initials: J
authors.lastname: Wirtschafter
mesh_terms: D000818:Animals; D002045:Bupivacaine / Q000008:administration & dosage / Q000494:pharmacology*; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism*; D002452:Cell Count / Q000187:drug effects; D005143:Eyelids / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006821:Hyaluronoglucosaminidase / Q000494:pharmacology; D007124:Immunoenzyme Techniques; D007267:Injections; D009132:Muscles / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009469:Neuromuscular Junction / Q000187:drug effects; D011817:Rabbits; D012038:Regeneration
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D006821:Hyaluronoglucosaminidase; D002045:Bupivacaine