Opioids confer myocardial tolerance to ischemia: Interaction of delta opioid agonists and antagonists

Background: Mammalian hibernation biology is now known to be mediated by de lta opioids. The altered myocellular physiology of hibernation closely para llels that of hypothermic ischemia used to protect the heart for cardiac su rgery. Methods and Results: The present study examined the interaction of delta op ioid agonists and antagonists on myocardial tolerance to ischemia. By means of a nonhibernating isolated rabbit heart model, functional and metabolic myocardial parameters were assessed during nonischemic baseline and postisc hemic recovery periods. Control hearts with standard cardioplegic protectio n alone were compared with those with cardioplegia plus preperfusion with a delta opioid agonist, a delta opioid antagonist, or both. All hearts were then subjected to 2 hours of global ischemia. Compared with cardioplegia al one, postischemic left ventricular developed pressure, coronary flows, and myocardial oxygen consumption were all increased with administration of del ta opioid agonists and decreased below baseline with delta opioid antagonis ts. Functional recovery of left ventricular developed pressure was improved with opioids (control hearts: 36 +/- 3 nun Hg vs hearts with cardioplegia plus delta opioid agonist: 65 +/- 5 mm Hg, P <.01) and inhibited with antag onists (control hearts: 36 3 mm Hg vs hearts with cardioplegia plus delta o pioid antagonist: 17 +/- 5 mm Hg, P <.05), rind true to form, the protectiv e opioid effect was negated when combined with an antagonist (control heart s: 36 3 mm Hg vs hearts with cardioplegia plus delta opioid agonist and del ta opioid antagonist: 42 +/- 4 mm Hg, P = not significant). Conclusions: This study demonstrates that cardiac tolerance to ischemia may be mediated by delta opioids.