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.
Not only the prevalence, but also the death rate from the coronary heart disease, including myocardial infarction, is higher in older people than among young people. A demographic shift towards an aging population will lead to a further increase in the prevalence of cardiovascular diseases among the elderly population. Therefore, one of the urgent aims of modern experimental and clinical medicine is to develop methods aimed at limiting reversible and irreversible damage to the myocardium, including in elderly patients. There are a lot of the data supporting the cardioprotective efficiency of such phenomena as ischemic and pharmacological pre- and postconditioning that reduce ischemic and reperfusion damage in young hearts. However, the information on the effectiveness of these phenomena in experiments on old animals is very scarce, contradictory, and not fully understood. The aim of the study was to experimentally evaluate the influence of old age on the reproducibility of the cardioprotective efficiency of pharmacological postconditioning using lactic acid in ischemia-reperfusion of the myocardium. In the course of the study, it was found that neutral lactate, after being administered into the blood flow of animals at a dose of 10 mg/kg 25 minutes after the onset of reperfusion, leads to a decrease in the infarct size of the left ventricle of the myocardium in old rats. Pharmacological postconditioning using lactate is not effective in reducing the duration of cardiac arrhythmias in ischemia-reperfusion of the myocardium in old rats; however, there is a tendency to reduce the incidence of reperfusion arrhythmias and the total duration of cardiac arrhythmias. The obtained data suggest that the presence of such a risk factor for cardiovascular diseases as old age is not a criterion to exclude the use of pharmacological postconditioning with lactate as a way to reduce ischemia and reperfusion injury of myocardium.
новых эффективных методов предотвращения или ослабления ишемического повреждения миокарда и механизмов их реализации является актуальной задачей современной экспериментальной и клинической медицины и важным направлением исследований в физиологии. Целью исследования было выявление воспроизводимости противоишемического и антиаритмического эффектов дистантного ишемического прекондиционирования (ДИПК) миокарда у крыс с экспериментальной дислипидемией (ДЛЕ). Установлено, что ДИПК не эффективно в плане ограничения размеров зоны некроза в миокарде левого желудочка при ишемии-реперфузии миокарда у крыс с ДЛЕ. В то же время после воспроизведения ДИПК у крыс с ДЛЕ имеет место выраженный антиаритмический эффект, о чем свидетельствует снижение длительности ишемических нарушений сердечного ритма на 85 % (p < 0,05). Полученные данные дают основание говорить о необходи-< 0,05). Полученные данные дают основание говорить о необходи-0,05). Полученные данные дают основание говорить о необходи-0,05). Полученные данные дают основание говорить о необходимости дифференцированного подхода к назначению ДИПК пациентам с острым инфарктом миокарда. Наличие такого фактора риска сердечно-сосудистых заболеваний, как ДЛЕ, может служить критерием для исключения ДИПК в качестве способа уменьшения ишемических и реперфузионных повреждений миокарда у пациентов с острым инфарктом миокарда. Ключевые слова: противоишемический эффект, антиаритмический эффект, дистантное ишемическое прекондиционирование, дислипидемия, зона риска, зона некроза Для цитирования: Кардиопротекторная эффективность дистантного ишемического прекондиционирования при ишемии-реперфузии миокарда у крыс с экспериментальной дислипидемией / Ф. И. Висмонт [и др.] // Вес. Нац. aкад. навук Беларусі.
Modern medicine faces the problem of a steady growth of cardiovascular pathology. Given the high medical and social significance of the problem of treating patients with coronary heart disease and acute myocardial infarction, the search for new effective methods to prevent or mitigate ischemic myocardial damage and mechanisms for their implementation is an urgent task of modern experimental and clinical medicine. The aim of the study was to determine the significance of nitric monoxide in realizing the infarction-limiting effect of remote ischemic postconditioning (RIPostC) in myocardial ischemia-reperfusion in young and old rats. The study revealed that RIPostC has a heart attack-limiting effect in myocardial ischemia-reperfusion in both young and old rats; however, under the conditions of the systemic action of the NG-nitro-L-arginine methyl ester inhibitor at a dose of 25 mg/kg (intravenous administration 5 min before the start of reperfusion and 15 min before RIPostC), the effect remains, although not completely, in old rats but not in young rats. Apparently, the NO synthase activity and the blood level of nitric monoxide play a more significant role in the mechanisms of the cardioprotective effects of RIPostC in young rats than in old rats.
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