Myocardial protection by ischemic preconditioning and δ-opioid receptor activation in the isolated working rat heart

Abstract

Objective: δ-Opioid receptors are involved in the cardioprotective effect of ischemic preconditioning. This study was designed (1) to assess the protective capacities of ischemic preconditioning and the synthetic δ-opioid receptor agonist D-Ala2-D-Leu5 enkephalin (DADLE) in a functionally oriented experimental model of ischemia and reperfusion and (2) to assess whether the effects of both protective measures are similarly blocked by naloxone, a nonspecific δ-opioid receptor antagonist. Methods: Sixty-four isolated working rat hearts were subjected to 45 minutes of hypothermic ischemia at 30°C followed by 25 minutes of normothermic reperfusion. Rats were pretreated with DADLE (1 mg/kg body weight intravenously), naloxone (3 mg/kg body weight intravenously), or a combination thereof within 60 minutes before onset of isolated heart perfusion. During the preischemic perfusion period, 8 hearts per group were preconditioned by one cycle of 5 minutes of normothermic global ischemia and subsequent reperfusion whereas another 8 served as nonpreconditioned controls. The postischemic functional recovery of hearts and their creatine kinase leakage were determined. Results: Pretreatment with DADLE and ischemic preconditioning improved the postischemic recovery of aortic flow when compared with nonpreconditioning (57.7% ± 4.0% and 60.8% ± 4.3% vs 40.0% ± 4.2% of preischemic baseline value, P