title: Effect of a pharmacologically induced decrease in core temperature in rats resuscitated from cardiac arrest.
abstract: OBJECTIVE
  Hypothermia is recommended by international guidelines for treatment of unconscious survivors of cardiac arrest to improve neurologic outcomes. However, temperature management is often underutilized because it may be difficult to implement. The present study evaluated the efficacy of pharmacologically induced hypothermia on survival and neurological outcome in rats resuscitated from cardiac arrest.
  
  
  METHODS
  Cardiac arrest was induced for 10 min in 120 rats. Sixty-one rats were resuscitated and randomized to normothermia, physical cooling or pharmacological hypothermia 5 min after resuscitation. Pharmacological hypothermia rats received a combination of ethanol, vasopressin and lidocaine (HBN-1). Physical hypothermia rats were cooled with intravenous iced saline and cooling pads. Rats in the pharmacological hypothermia group received HBN-1 at ambient temperature (20 °C). Normothermic rats were maintained at 37.3 ± 0.2 °C.
  
  
  RESULTS
  HBN-1 (p < 0.0001) shortened the time (85 ± 71 min) to target temperature (33.5 °C) versus physical hypothermia (247 ± 142 min). The duration of hypothermia was 17.0 ± 6.8h in the HBN-1 group and 17.3 ± 7.5h in the physical hypothermia group (p = 0.918). Survival (p = 0.034), neurological deficit scores (p < 0.0001) and Morris Water Maze performance after resuscitation (p = 0.041) was improved in the HBN-1 versus the normothermic group. HBN-1 improved survival and early neurological outcome compared to the physical hypothermia group while there was no significant difference in performance in the Morris water maze.
  
  
  CONCLUSIONS
  HBN-1 induced rapid and prolonged hypothermia improved survival with good neurological outcomes after cardiac arrest suggesting that pharmacologically induced regulated hypothermia may provide a practical alternative to physical cooling.
authors.affiliation: Department of Emergency Medicine, University of North Carolina School of Medicine, United States. Electronic address: lkatz@med.unc.edu.
authors.forename: Laurence M
authors.initials: LM
authors.lastname: Katz
authors.affiliation: Department of Emergency Medicine, University of North Carolina School of Medicine, United States.
authors.forename: Jonathan E
authors.initials: JE
authors.lastname: Frank
authors.affiliation: Department of Emergency Medicine, University of North Carolina School of Public Health, United States.
authors.forename: Lawrence T
authors.initials: LT
authors.lastname: Glickman
authors.affiliation: Epidemiology, University of Alabama at Birmingham, United States.
authors.forename: Gerald
authors.initials: G
authors.lastname: McGwin
authors.affiliation: Epidemiology, University of Alabama at Birmingham, United States.
authors.forename: Brice H
authors.initials: BH
authors.lastname: Lambert
authors.affiliation: Neurotoxicology Branch, US Environmental Protection Agency, Research Triangle Park, NC, United States.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Gordon
mesh_terms: D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D001831:Body Temperature / Q000187:drug effects*; D016887:Cardiopulmonary Resuscitation / Q000379:methods*; D004195:Disease Models, Animal; D004338:Drug Combinations; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D006323:Heart Arrest / Q000503:physiopathology / Q000628:therapy*; D007036:Hypothermia, Induced / Q000379:methods*; D008012:Lidocaine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014667:Vasopressins / Q000494:pharmacology*
chemical_list: D000779:Anesthetics, Local; D004338:Drug Combinations; D014662:Vasoconstrictor Agents; D014667:Vasopressins; D000431:Ethanol; D008012:Lidocaine
keywords: Cardiac arrest; Hypothermia; Resuscitation