The infarct-limiting efficacy of deltorphin-II in old rats with diet-induced metabolic syndrome

Abstract

Background. The discovery of new pharmacological agents for myocardial protection during reperfusion injury is an urgent goal of modern physiology and pharmacology.The aim of the study. To identify the potential for protecting the myocardium from reperfusion injury by administering the delta-2 opioid receptor agonist deltorphin-II prior to reperfusion in old rats with diet-induced metabolic syndrome.Materials and methods. The study was performed on Wistar rats aged 60 days (young rats) and 450 days (old rats) before the onset of a study. Metabolic syndrome (MetS) was modeled for 84 days with a high-carbohydrate high-fat diet (16 % protein, 21 % fat, 46 % carbohydrate) with the replacement of drinking water with 20 % fructose solution. Myocardial infarction was performed by 45-min coronary occlusion followed by 120-min reperfusion; the size of the area of the necrotic myocardium was determined relative to the size of the hypoperfusion zone. The delta-2 opioid receptor agonist deltorphin-II was administered once intravenously 5 minutes before the end of ischemia.Results. It was found that coronary occlusion and subsequent reperfusion both in groups of young and old rats led to the formation of myocardial infarction (necrosis), the size of which was 45 % of the size of the risk zone. Administration of deltorphin-II in old rats led to a limitation of infarct size to 30 % of the size of the risk zone, i. e. 1.7-fold. The use of deltorphin-II in old rats with MetS contributed to a decrease in infarct size to 27 % of the size of the risk zone (1.5 times). The obtained results demonstrate the cardioprotective efficacy of the delta-2 opioid receptor agonist deltorphin-II in aging and metabolic syndrome in rats.Conclusions. These data may serve as a basis for conducting preclinical studies of deltorphin-II as a drug for treatment of acute myocardial infarction.

δ-Opioid Receptor as a Molecular Target for Increasing Cardiac Resistance to Reperfusion in Drug Development

“…The infarct-limiting effect of deltorphin II was confirmed in rats with diet-induced metabolic syndrome and in aged rats with a coronary artery occlusion (45 min) and reperfusion (120 min) in vivo [24].…”