Role of δ-opioid receptor agonists on infarct size reduction in swine

Opioids are involved in cardiac ischemic preconditioning. Important species differences in cellular signaling mechanisms, antiarrhythmic, and antistunning effects have been described. The role of the δ-opioid receptor activation in swine remains unknown. Forty minutes before a 45-min occlusion and 180-min reperfusion of the left anterior descending coronary artery, open-chest, pentobarbital-anesthetized swine received either 1) saline (controls); 2) [D-Ala²,D-Leu⁵]enkephalin (DADLE); 3) [D-Pen^2,5]enkephalin (DPDPE); 4) deltorphin-D, a novel δ₂-opioid agonist; or 5) ischemic preconditioning (IP). Assessed were 1) infarct size to area at risk (IS, triphenyltetrazolium staining), 2) regional and global myocardial function (sonomicrometry, ventricular pressure catheters), and 3) arrhythmias (electrocardiogram analyses). It was found that DPDPE and deltorphin-D pretreatment reduced IS from 64.7 ± 5 to 36.5 ± 6% and 27.4 ± 11% (P < 0.01), respectively, whereas DADLE had no effect (66.8 ± 3%). Both IP and DADLE had a proarrhythmic effect (P < 0.01). However, no differences in global or regional myocardial function or arrhythmia scores were observed between groups. This suggests that δ-receptor-specific opioids provide cardioprotection in swine.