Role of Endogenous Opioid System in Ischemic-Induced Late Preconditioning.

BACKGROUND: Opioid receptors (OR) are involved in myocardial late preconditioning (LPC) induced by morphine and δ1-opioid receptor (δ1-OR) agonists. The role of OR in ischemic-induced LPC is unknown. We investigated whether 1) OR are involved in the trigger and/or mediation phase of LPC and 2) a time course effect on the expression of different opioid receptors and their endogenous ligands exists. METHODS: Male Wistar rats were randomly allocated to four groups (each group n = 8). Awake animals were ischemic preconditioned by a 5 minutes coronary occlusion. 24 hours later, anesthetized animals underwent 25 minutes coronary occlusion followed by 2 hours of reperfusion. The role of OR was investigated by treatment with intraperitoneal naloxone (Nal) 10 minutes prior to LPC (Nal-LPC; trigger phase) or 10 min prior to sustained ischemia (LPC-Nal; mediation phase). RESULTS: LPC reduced infarct size from 61±10% in controls to 25±9% (P<0.001). Naloxone during trigger or mediation phase completely abolished LPC-induced cardioprotection (59±9% and 62±9%; P<0.001 vs. LPC). 8, 12 and 24 hours after the ischemic stimulus, expression of δ-OR in the heart was increased, whereas µ-opioid receptor (µ-OR) and κ-opioid receptor (κ-OR) were not. Plasma concentrations of ß-endorphin and leu-enkephalin but not dynorphin were increased by LPC. CONCLUSION: Ischemic LPC is triggererd and mediated by OR. Expression of δ-OR and plasma levels of endogenous opioid peptides are increased after ischemic LPC.

Metabolic monitoring of postischemic myocardium during intermittent warm-blood cardioplegic administration.

In 12 patients undergoing elective myocardial revascularization with intermittent administration of warm-blood cardioplegic solution for myocardial protection, we analyzed metabolic changes by assay of global ischemia indicators (pH, lactate, glucose, and potassium), which we measured in the coronary sinus and arterial blood during the ischemic and postischemic periods. A typical cumulative ischemic pattern with progressively decreasing pH values and progressively increasing lactate values could not be observed in all patients. It was not the degree of lactate washout, but the lactate concentration at the end of each reperfusion, that correlated significantly with global metabolic recovery time, which suggests the importance of effective reperfusion.