Opioid preconditioning: Myocardial function and energy metabolism

Background. Opioid receptor agonists are involved in ischemic preconditioni ng and natural hibernation. The aim of this study was to determine whether pretreatment with D-Ala2-Leu5-enkephalin or morphine confers cardioprotecti on in large mammalian hearts. We assessed myocardial functional recovery an d global energy metabolism after ischemic cold storage. Methods. After pretreatment with D-Ala2-Leu5-enkephalin, morphine sulfate, or saline (n = 6 each), swine hearts were excised and stored for 75 minutes at 4 degreesC, then reperfused in a four-chamber isolated working heart ap paratus. Serial myocardial biopsies were performed to assess cellular energ y metabolism. Results. Improved systolic (cardiac output, contractility) and diastolic (t au) left ventricular functions were observed in hearts pretreated with D-Al a2-Leu5-enkephalin or morphine. These benefits were not correlated with cha nges in high-energy phosphate levels. Cardiac enzyme leakage (creatine kina se, troponin-I) was similar among treated and control groups. Lactate efflu x increased significantly in controls, but not in opioid-pretreated hearts (p < 0.01) at 75 minutes of reperfusion. Conclusions. D-Ala2-Leu5-enkephalin and morphine pretreatments improve post ischemic function after cold storage of swine hearts. Postischemic lactate reduction, but not high-energy phosphate levels, may account for the observ ed cardioprotective effects. (C) 2001 by The Society of Thoracic Surgeons.