title: Mechanism by which activation of delta-opioid receptor reduces the severity of postresuscitation myocardial dysfunction.
abstract: OBJECTIVE
  Postresuscitation myocardial dysfunction has been recognized as a leading cause of early death after initially successful cardiopulmonary resuscitation. We have previously demonstrated that opening adenosine triphosphate (ATP)-sensitive K (KATP) channels or activation of delta-opioid receptors minimized the severity of postresuscitation myocardial dysfunction and increased the duration of postresuscitation survival. In the present study, we investigated the potential mechanism of myocardial protection following delta-opioid receptor activation in a rat model of cardiac arrest and cardiopulmonary resuscitation.
  
  
  METHODS
  Randomized prospective animal study.
  
  
  METHODS
  Animal research laboratory.
  
  
  METHODS
  Male Sprague-Dawley rats.
  
  
  METHODS
  Ventricular fibrillation was induced in 24 Sprague-Dawley rats. Mechanical ventilation and precordial compression were initiated after 8 mins of untreated ventricular fibrillation. Defibrillation was attempted after 6 mins of cardiopulmonary resuscitation. The animals were randomized to four groups: a) pentazocine (0.3 mg/kg), a delta-opioid receptor agonist; b) pentazocine pretreated with KATP channel blocker, glibenclamide (0.3 mg/kg), administered 45 mins before induction of ventricular fibrillation; c) glibenclamide pretreated alone 45 mins before induction of ventricular fibrillation; and d) placebo. Pentazocine or saline placebo was injected into the right atrium after 5 mins of untreated ventricular fibrillation.
  
  
  RESULTS
  Postresuscitation myocardial function, as measured by the rate of left ventricular pressure increase at 40 mm Hg, left ventricular end-diastolic pressure, and cardiac index, was significantly improved in pentazocine-treated animals. This was associated with significantly prolonged duration of survival. Except for ease of defibrillation, the beneficial effects of pentazocine were abolished by pretreatment with the KATP channel blocker glibenclamide.
  
  
  CONCLUSIONS
  The postresuscitation myocardial protective effects provided by activation of delta-opioid receptor may be mediated via opening KATP channels.
authors.affiliation: Weil Institute of Critical Care Medicine, Rancho Mirage, CA, USA.
authors.forename: Xiangshao
authors.initials: X
authors.lastname: Fang
authors.forename: Wanchun
authors.initials: W
authors.lastname: Tang
authors.forename: Shijie
authors.initials: S
authors.lastname: Sun
authors.forename: Lei
authors.initials: L
authors.lastname: Huang
authors.forename: Zitong
authors.initials: Z
authors.lastname: Huang
authors.forename: Max Harry
authors.initials: MH
authors.lastname: Weil
mesh_terms: D000255:Adenosine Triphosphate; D000704:Analysis of Variance; D000818:Animals; D009202:Cardiomyopathies / Q000209:etiology / Q000517:prevention & control*; D016887:Cardiopulmonary Resuscitation; D002316:Cardiotonic Agents / Q000494:pharmacology*; D006323:Heart Arrest / Q000628:therapy*; D008297:Male; D015221:Potassium Channels / Q000187:drug effects; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D017465:Receptors, Opioid, delta / Q000819:agonists*; D016019:Survival Analysis
chemical_list: D002316:Cardiotonic Agents; D015221:Potassium Channels; D017465:Receptors, Opioid, delta; D000255:Adenosine Triphosphate