title: L-carnitine reduces susceptibility to bupivacaine-induced cardiotoxicity: an experimental study in rats.
abstract: BACKGROUND
  The primary aim of this study was to evaluate the effect of acute administration of L-carnitine 100 mg·kg-1iv on susceptibility to bupivacaine-induced cardiotoxicity in rats.
  
  
  METHODS
  In the first of two experiments, L-carnitine 100 mg·kg-1iv (n = 10) or saline iv (n = 10) was administered to anesthetized and mechanically ventilated Sprague-Dawley rats following which an infusion of bupivacaine 2.0 mg·kg-1·min-1iv was given until asystole occurred. The primary outcome was the probability of survival. Secondary outcomes included times to asystole, first dysrhythmia, and to 50% reductions in heart rate (HR) and mean arterial pressure (MAP). To determine whether the same dose of L-carnitine is effective in treating established bupivacaine cardiotoxicity, we also conducted a second experiment in which bupivacaine 20 mg·kg-1iv was infused over 20 sec. Animals (n = 10 per group) received one of four iv treatments: 30% lipid emulsion 4.0 mL·kg-1, L-carnitine 100 mg·kg-1, 30% lipid emulsion plus L-carnitine, or saline. The primary outcome was the return of spontaneous circulation (ROSC) during resuscitation.
  
  
  RESULTS
  In the first study, L-carnitine 100 mg·kg-1increased the probability of survival during bupivacaine infusion (hazard ratio, 12.0; 95% confidence interval, 3.5 to 41.5; P < 0.001). In L-carnitine-treated animals, the times to asystole, first dysrhythmia, and to 50% reductions in HR and MAP increased by 33% (P < 0.001), 65% (P < 0.001), 71% (P < 0.001), and 63% (P < 0.001), respectively. In the second study, no animal in the control or L-carnitine alone groups achieved ROSC when compared with the lipid emulsion groups (P < 0.01).
  
  
  CONCLUSIONS
  These findings suggest that acute administration of L-carnitine 100 mg·kg-1decreases susceptibility to bupivacaine cardiotoxicity, but is ineffective during resuscitation from bupivacaine-induced cardiac arrest.
authors.affiliation: Department of Anesthesia and Pain Medicine, The Hospital For Sick Children, University of Toronto, 555 University Avenue, Toronto, ON, M5G 1X8, Canada. gail.wong@health.nsw.gov.au.
authors.forename: Gail K
authors.initials: GK
authors.lastname: Wong
authors.affiliation: Department of Anesthesia and Pain Medicine, The Hospital For Sick Children, University of Toronto, 555 University Avenue, Toronto, ON, M5G 1X8, Canada.
authors.forename: Carolyne
authors.initials: C
authors.lastname: Pehora
authors.affiliation: Department of Anesthesia and Pain Medicine, The Hospital For Sick Children, University of Toronto, 555 University Avenue, Toronto, ON, M5G 1X8, Canada.
authors.forename: Mark W
authors.initials: MW
authors.lastname: Crawford
mesh_terms: D000818:Animals; D002045:Bupivacaine / Q000633:toxicity*; D066126:Cardiotoxicity / Q000517:prevention & control*; D002331:Carnitine / Q000494:pharmacology*; D006801:Humans; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002331:Carnitine; D002045:Bupivacaine