δ-Opioid receptor agonist reduces severity of postresuscitation myocardial dysfunction

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Abstract
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 δ-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 δ-opioid receptor agonist pentazocine (300 μg/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 δ-opioid receptor agonist is a novel and promising intervention for minimizing global ischemic injury during CPR and postresuscitation myocardial dysfunction.