title: Epinephrine prevents muscle blood flow increases after perineural injection of tetrodotoxin.
abstract: BACKGROUND
  The local anesthetic properties of tetrodotoxin, a potent naturally occurring sodium channel blocker, have been recently reexamined. It was found that sciatic nerve block duration could be greatly increased and systemic toxicity greatly decreased if epinephrine was injected with tetrodotoxin. The mechanism that underlies epinephrine-mediated prolongation of tetrodotoxin nerve blocks is not known, but indirect evidence suggests that epinephrine may slow the clearance of tetrodotoxin from the site of injection. The authors hypothesized that tetrodotoxin causes vasodilatation at its injection site, which accelerates its systemic uptake, and that this vasodilatation is attenuated by coinjected epinephrine.
  
  
  METHODS
  The radiolabeled microsphere technique was used to measure tissue blood flow in anesthetized rats before and after perisciatic injection of tetrodotoxin alone and in combination with epinephrine.
  
  
  RESULTS
  Tetrodotoxin, in a dose of 0.1 ml of a 60 microM solution, significantly increased blood flow in perisciatic muscle at the injected side compared with simultaneous contralateral control and ipsilateral preinjection baseline. Tetrodotoxin did not increase blood flow in the sciatic nerve. Coinjection of epinephrine with tetrodotoxin prevented tetrodotoxin-induced increases in perisciatic muscle blood flow over time and did not alter sciatic nerve blood flow. Arterial blood pressure was maintained with this dose of tetrodotoxin, although brain blood flow decreased. Coinjection of epinephrine with tetrodotoxin prevented decreases in brain blood flow. Higher doses of tetrodotoxin produced hypotension.
  
  
  CONCLUSIONS
  Vasoconstriction in the perisciatic muscles by epinephrine may contribute to the prolongation of tetrodotoxin-induced sciatic nerve blocks and the reduction of systemic toxicity of tetrodotoxin.
authors.affiliation: Department of Anesthesiology, Perioperative and Pain Medicine, Children's Hospital, Boston, MA, USA.
authors.forename: Takako
authors.initials: T
authors.lastname: Masuda
authors.forename: Brian E
authors.initials: BE
authors.lastname: Cairns
authors.forename: Senthilkumar
authors.initials: S
authors.lastname: Sadhasivam
authors.forename: Patricia S
authors.initials: PS
authors.lastname: Dunning
authors.forename: Charles B
authors.initials: CB
authors.lastname: Berde
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000779:Anesthetics, Local / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000818:Animals; D002245:Carbon Dioxide / Q000097:blood; D002560:Cerebrovascular Circulation / Q000187:drug effects; D004837:Epinephrine / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D007267:Injections; D008297:Male; D008863:Microspheres; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D012584:Sciatic Nerve; D013779:Tetrodotoxin / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects
chemical_list: D000316:Adrenergic alpha-Agonists; D000779:Anesthetics, Local; D002245:Carbon Dioxide; D013779:Tetrodotoxin; D004837:Epinephrine