title: Is cardiolipin the target of local anesthetic cardiotoxicity?
abstract: OBJECTIVE
  Local anesthetics are used broadly to prevent or reverse acute pain and treat symptoms of chronic pain. Local anesthetic-induced cardiotoxic reaction has been considered the accidental event without currently effective therapeutic drugs except for recently reported intralipid infusion whose possible mechanism of action is not well known.
  
  
  BACKGROUND
  Cardiolipin, an anionic phospholipid, plays a key role in determining mitochondrial respiratory reaction, fatty acid metabolism and cellular apoptosis. Mitochondrial energy metabolism dysfunction is suggested as associated with local anesthetic cardiotoxicity, from an in vitro study report that the local anesthetic cardiotoxicity may be due to the strong electrostatic interaction of local anesthetics and cardiolipin in the mitochondria membrane, although there is a lack for experimental evidence. Herein we hypothesized that local anesthetic-cardiolipin interactions were the major determinant of local anesthetic-associated cardiotoxic reaction, established by means of theoretic and structural biological methods. This interacting model would give an insight on the underlying mechanism of local anesthetic cardiotoxicity and provide clues for further in depth research on designing preventive drugs for such inadvertent accidence in routine clinical practice.
  
  
  CONCLUSIONS
  The interaction between local anesthetic and mitochondrial cardiolipin may be the underlying mechanism for cardiotoxicity affecting its energy metabolism and electrostatic status.
authors.affiliation: Departmento de Anestesiologia do Affiliated Nanjing Maternity and Child Health Care Hospital, Nanjing Medical University.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Shen
authors.forename: Fuzhou
authors.initials: F
authors.lastname: Wang
authors.forename: Shiqin
authors.initials: S
authors.lastname: Xu
authors.forename: Yanning
authors.initials: Y
authors.lastname: Qian
authors.forename: Yusheng
authors.initials: Y
authors.lastname: Liu
authors.forename: Hongmei
authors.initials: H
authors.lastname: Yuan
authors.forename: Qingsong
authors.initials: Q
authors.lastname: Zhao
authors.forename: Shanwu
authors.initials: S
authors.lastname: Feng
authors.forename: Xirong
authors.initials: X
authors.lastname: Guo
authors.forename: Jianguo
authors.initials: J
authors.lastname: Xu
authors.forename: Jie
authors.initials: J
authors.lastname: Yang
mesh_terms: D000779:Anesthetics, Local / Q000494:pharmacology*; D002308:Cardiolipins / Q000187:drug effects*; D006331:Heart Diseases / Q000139:chemically induced*; D006801:Humans; D008929:Mitochondria, Heart / Q000187:drug effects
chemical_list: D000779:Anesthetics, Local; D002308:Cardiolipins