Role of delta-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 delta-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-Ala(2),D-Leu(5)]enkephalin (DADLE); 3) [D-Pen(2,5)]enkephalin (DPDPE); 4) deltorphin-D, a novel delta(2)-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 delta-receptor-specific opioids provide cardioprotection in swine.
Sigg
Daniel C
DC
Department of Anesthesiology, University of Minnesota, Minneapolis, Minnesota 55455, USA.
Coles
James A
JA
Oeltgen
Peter R
PR
Iaizzo
Paul A
PA
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000453:epidemiology; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D004562:Electrocardiography; D020881:Enkephalin, D-Penicillamine (2,5)- / Q000627:therapeutic use; D016308:Enkephalin, Leucine-2-Alanine / Q000627:therapeutic use; D006439:Hemodynamics; D019157:Ischemic Preconditioning, Myocardial; D009203:Myocardial Infarction / Q000473:pathology* / Q000503:physiopathology; D017202:Myocardial Ischemia; D015425:Myocardial Reperfusion; D009842:Oligopeptides / Q000627:therapeutic use; D017465:Receptors, Opioid, delta / Q000819:agonists* / Q000502:physiology*; D013045:Species Specificity; D013552:Swine; D017725:Ventricular Pressure
D002316:Cardiotonic Agents; D009842:Oligopeptides; D017465:Receptors, Opioid, delta; C059567:deltorphin; D016308:Enkephalin, Leucine-2-Alanine; D020881:Enkephalin, D-Penicillamine (2,5)-