Remote postconditioning (RPost) has a great therapeutic potential for protecting the myocardium during ischemiareperfusion in clinical practice. At the same time, an important problem limiting the use of conditioning effects in the clinic is the presence of metabolic disorders in the patient. The aim of this work was to assess the effect of induced metabolic syndrome (iMetS) on the efficacy of the infarct-limiting effect of remote ischemic postconditioning (RPost) in rats and to study the mechanisms of this effect.The study was carried out on Wistar rats. MetS was induced by high-carbohydrate high-fat diet. Criteria of metabolic syndrome were an increase in the weight of animals, abdominal fat volume, the development of arterial hypertension, hypercholesterolemia, an increase in triglycerides in serum, hyperleptinemia, hyperglycemia, the development of a state of insulin resistance by a significant increase in the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) index and glucose tolerance. All animals were subjected to 45 min coronary occlusion and 120 min reperfusion.RPost led to a twofold reduction of infarct size in rats with intact metabolism (р < 0.0001), while in rats with iMetS a decrease in infarct size during RPost was 25 % (p = 0.00003), which was significantly lower than in animals without iMetC (р < 0.0001). A direct correlation was found between of infarct size during RPost and the serum leptin level of rats with iMetC.The presented data suggested that a decrease in the efficiency of remote postconditioning in rats with diet-induced metabolic syndrome depends on leptin content in blood.
The role of reactive oxygen species (ROS) in ischemic and reperfusion (I/R) injury of the heart has been discussed for more than 40 years. It has been demonstrated that reperfusion triggers a multiple increase in free radical generation in the isolated heart. Antioxidants were found to have the ability to mitigate I/R injury of the heart. However, it is unclear whether their cardioprotective effect truly depends on the decrease of ROS levels in myocardial tissues. Since high doses and high concentrations of antioxidants were experimentally used, it is highly likely that the cardioprotective effect of antioxidants depends on their interaction not only with free radicals but also with other molecules. It has been demonstrated that the antioxidant N-2-mercaptopropionyl glycine or NDPH oxidase knockout abolished the cardioprotective effect of ischemic preconditioning. Consequently, there is evidence that ROS protect the heart against the I/R injury.
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.
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