Role of δ-opioid receptors in hydromorphone postconditioning-induced maintenance of electrophysiological stability during ischemia-reperfusion in isolated rat hearts

Abstract

Objective To evaluate the role of δ-opioid receptors in hydromorphone postconditioning-induced maintenance of electrophysiological stability during ischemia-reperfusion (I/R) in isolated rat hearts. Methods Healthy male Sprague-Dawley rats, aged 2-3 months, weighing 280-360 g, were used in this study.The animals were anesthetized with intraperitoneal pentobarbital 60 mg/kg.Their hearts were immediately removed and perfused in a Langendorff apparatus.Thirty-two isolated hearts were divided into 4 groups after successful preparation of Langendorff perfusion model (n=8 each) using a random number table: control group (group C), group I/R, hydromorphone postconditioning group (group HP) and hydromorphone plus δ-opioid receptor antagonist naltridole postconditioning group (group HNP). In HP and HNP groups, the hearts were perfused for 10 min with K-H solution containing 4.1 ng/ml hydromorphone and 4.1 ng/ml hydromorphone plus 5 μmol/L naltridole, respectively, and then with K-H solution for 50 min.At 20 min of stabilization (T0) and 10, 25 and 60 min of reperfusion (T1-2), heart rate (HR), monophasic action potential (MAP) duration at 90% repolarization (MAPD90) of the two layers (endocardium, epicardium) of the anterior left ventricular wall were recorded.Transmural dispersion of repolarization (TDR) was calculated.The development of arrhythmia, time for restoration of spontaneous heart beat and duration of arrhythmia were recorded during the period of reperfusion. Results Compared with group C, MAPD90 of endocardium at T1-2 and MAPD90 of epicardium at T1 were significantly prolonged in I/R and HP groups, HR was significantly decreased at T2-3, MAPD90 of endocardium and epicardium was prolonged at T1-3 in group HNP, TDR was significantly enlarged at T1 in group I/R and at T2 in group HNP, and TDR was decreased at T3 in group HP (P 0.05), the time for restoration of spontaneous heart beat was significantly shortened, and TDR was decreased at T1 in HP and HNP groups, duration of arrhythmia was significantly shortened, and MAPD90 of endocardium was shortened at T1 in group HP, and HR was significantly decreased at T2-3, MAPD90 of endocardium and epicardium was prolonged at T1-3, and TDR was decreased at T2-3 in group HNP (P 0.05), HR was significantly decreased at T2-3, MAPD90 of endocardium and epicardium was prolonged at T1-3, and TDR was increased at T3 in group HNP (P<0.05). Conclusion The mechanism underlying hydromorphone postconditioning-induced maintenance of electrophysiological stability during I/R is related to activating δ-opioid receptors in isolated rat hearts. Key words: Receptors, opioid, delta; Hydromorphone; Postconditioning; Myocardial reperfusion injury; Cardiac electrophysiology