title: Concentration-dependent bupivacaine myotoxicity in rabbit extraocular muscle.
abstract: OBJECTIVE
  Bupivacaine myotoxicity to the extraocular muscles, from retrobulbar or peribulbar anesthesia, has been reported after cataract surgery and other intraocular procedures. However, there are no data on the concentration-dependence of bupivacaine in causing extraocular muscle toxicity.
  
  
  METHODS
  Six aged rabbits received different concentrations of bupivacaine (0.75% and lower) in 3 extraocular muscles, namely, superior rectus, inferior rectus, and inferior oblique muscles of each rabbit's eye. The animals were euthanized at 5 days or 1 month after the injections. Hematoxylin and eosin- and Masson trichrome-stained sections were obtained from the involved extraocular muscles after paraffin embedding.
  
  
  RESULTS
  Five days after the initial injection, the 0.75% bupivacaine-injected extraocular muscles showed extensive myonecrosis and degeneration with early-stage regenerating muscle fibers. However, muscle tissue injected with half-concentration bupivacaine (0.38%) showed scattered and significantly fewer areas of mild muscle fiber degeneration with regeneration. There were no areas of muscle tissue degeneration observed in any muscle injected with quarter-concentration bupivacaine (0.19%). At 1 month, however, only 0.75% bupivacaine-injected muscles displayed areas of regenerated muscle fiber cells with foci of scar formation. There was no visible scar formation in muscles injected with any bupivacaine concentration lower than 0.75%, or with saline, at 1 month after injection.
  
  
  CONCLUSIONS
  Extraocular muscle injection with full-strength bupivacaine (0.75%) can cause myonecrosis and degeneration acutely, with regeneration appearing by 5 days, followed by some late-stage scar formation. However, no long-term effects were observed with bupivacaine concentrations of 0.38% or 0.19%.
authors.affiliation: The Krieger Children's Eye Center at the Wilmer Institute, The Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Baltimore, MD 21287, USA. czhang1@jhmi.edu
authors.forename: Cheng
authors.initials: C
authors.lastname: Zhang
authors.forename: Pittaya
authors.initials: P
authors.lastname: Phamonvaechavan
authors.forename: Anand
authors.initials: A
authors.lastname: Rajan
authors.forename: David Y
authors.initials: DY
authors.lastname: Poon
authors.forename: Pinar
authors.initials: P
authors.lastname: Topcu-Yilmaz
authors.forename: David L
authors.initials: DL
authors.lastname: Guyton
mesh_terms: D000779:Anesthetics, Local / Q000008:administration & dosage / Q000633:toxicity; D000818:Animals; D002045:Bupivacaine / Q000008:administration & dosage / Q000633:toxicity*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005500:Follow-Up Studies; D007273:Injections, Intramuscular; D009336:Necrosis / Q000139:chemically induced / Q000473:pathology; D009801:Oculomotor Muscles / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D011817:Rabbits
chemical_list: D000779:Anesthetics, Local; D002045:Bupivacaine