title: alpha-Methylnorepinephrine, a selective alpha2-adrenergic agonist for cardiac resuscitation.
abstract: OBJECTIVE
  The purpose of this study was to investigate the effects of a selective alpha2-adrenergic agonist, alpha-methylnorepinephrine (alphaMNE) as an alternative vasopressor agent during cardiopulmonary resuscitation (CPR).
  
  
  BACKGROUND
  For more than 40 years, epinephrine has been the vasopressor agent of choice for CPR. Its beta- and alpha1-adrenergic effects increase myocardial oxygen consumption, magnify global myocardial ischemia and increase the severity of postresuscitation myocardial dysfunction.
  
  
  METHODS
  Ventricular fibrillation (VF) was induced in 20 Sprague-Dawley rats. After 8 min of untreated VF, mechanical ventilation and precordial compression began. AlphaMNE, epinephrine or saline placebo was injected into the right atrium 2 min after the start of precordial compression. As an additional control, one group of animals was pretreated with alpha2-receptor blocker, yohimbine, before injection of alphaMNE. Defibrillation was attempted 4 min later. Left ventricular pressure, dP/dt40, negative dP/dt and cardiac index were measured for an interval of 240 min after resuscitation.
  
  
  RESULTS
  Except for saline placebo and yohimbine-treated animals, comparable increases in coronary perfusion pressure were observed after each drug intervention. All animals were successfully resuscitated. Left ventricular diastolic pressure, cardiac index, dP/dt40 and negative dP/dt were more optimal after alphaMNE; this was associated with significantly better postresuscitation survival. Pretreatment with vohimbine abolished the beneficial effects of alphaMNE.
  
  
  CONCLUSIONS
  The selective alpha2-adrenergic agonist, alphaMNE, was as effective as epinephrine for initial cardiac resuscitation but provided strikingly better postresuscitation myocardial function and survival.
authors.affiliation: Institute of Critical Care Medicine, Palm Springs, California 92262-5309, USA.
authors.forename: S
authors.initials: S
authors.lastname: Sun
authors.forename: M H
authors.initials: MH
authors.lastname: Weil
authors.forename: W
authors.initials: W
authors.lastname: Tang
authors.forename: T
authors.initials: T
authors.lastname: Kamohara
authors.forename: K
authors.initials: K
authors.lastname: Klouche
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D016887:Cardiopulmonary Resuscitation; D006323:Heart Arrest / Q000628:therapy*; D008297:Male; D008771:Nordefrin / Q000627:therapeutic use*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D014662:Vasoconstrictor Agents / Q000627:therapeutic use*; D017725:Ventricular Pressure / Q000187:drug effects; D015016:Yohimbine / Q000494:pharmacology
chemical_list: D000317:Adrenergic alpha-Antagonists; D014662:Vasoconstrictor Agents; D015016:Yohimbine; D008771:Nordefrin