Delta-opioid receptor agonist reduces severity of postresuscitation myocardial dysfunction.
Postresuscitation myocardial dysfunction is recognized as a leading cause of early death after initially successful cardiopulmonary resuscitation (CPR). In the present study, we hypothesized that a delta-opioid receptor agonist would decrease the severity of postresuscitation myocardial dysfunction and improve survival. Fifteen Sprague-Dawley rats, fasted overnight with access to water, were anesthetized by an injection of 45 mg/kg ip pentobarbital sodium. Additional doses of 10 mg/kg were administered at hourly intervals but not within 30 min before induced ventricular fibrillation (VF). Either the delta-opioid receptor agonist pentazocine (300 microg/kg), pentazocine pretreated with the opioid receptor-blocking agent naloxone (1 mg/kg), or saline placebo was injected into the right atrium after 5 min of untreated VF and 3 min before initiation of CPR. After an additional 8 min of CPR administration, defibrillation was attempted. All animals were successfully resuscitated. Left ventricular rate of pressure increase at 40 mmHg and cardiac index values were significantly improved in pentazocine-treated animals, which also had significantly longer survival times (60 +/- 11 vs. 16 +/- 7 h; P < 0.01). Except for ease of defibrillation, the beneficial effects of pentazocine were completely abolished by pretreatment with naloxone. The concept of pharmacological hibernation employing a delta-opioid receptor agonist is a novel and promising intervention for minimizing global ischemic injury during CPR and postresuscitation myocardial dysfunction.
Sun
Shijie
S
Institute of Critical Care Medicine, Palm Springs, CA 92262, USA. shijiesun@aol.com
Weil
Max Harry
MH
Tang
Wanchun
W
Kamohara
Takashi
T
Klouche
Kada
K
D000818:Animals; D009202:Cardiomyopathies / Q000209:etiology* / Q000503:physiopathology*; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D010423:Pentazocine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017465:Receptors, Opioid, delta / Q000819:agonists*; D012151:Resuscitation / Q000009:adverse effects*; D012720:Severity of Illness Index
D009292:Narcotic Antagonists; D017465:Receptors, Opioid, delta; D009270:Naloxone; D010423:Pentazocine