Respiration in isolated cardiomyocytes and microviscosity of their membranes in rats of different ages with heart failure

Abstract

Background. According to the latest epidemiological data, heart failure (HF) is diagnosed in 10% of adult population over 70 years old. However, currently this diagnosis is being increasingly made in young and middleaged people. The pathogenesis of HF may be based on a decrease in respiration in cardiomyocytes with age, which affects the function of energy-dependent processes in cells.Aim. To study respiration in cardiomyocytes and microviscosity of their membranes in rats aged 2 and 15 months with heart failure.Materials and methods. The study was carried out on male Wistar rats. The animals were divided into 4 groups: 2 groups of intact rats aged 2 and 15 months (n = 12) and 2 groups of animals of similar ages (n = 10) with a model of HF. In the latter, HF formed by day 28 after a double subcutaneous injection of isoproterenol hydrochloride at a dose of 170 mg / kg with an interval of 24 hours. Isolated cardiomyocytes were obtained from enzyme-washed rat hearts. Cell respiration was studied in a thermostated chamber in an incubation medium supplemented with phosphorylation (ADP) and oxidation (succinate) substrates. The respiratory control (RC) ratio was calculated by dividing V3 respiration state to V4. Membrane microviscosity characteristics were assessed by the eximerization coefficient of pyrene fluorescence in the areas of protein – lipid and lipid – lipid interactions.Results. RC in cardiomyocyte membranes of intact animals did not change with age. In 2-month-old rats with HF, respiratory control ratio (RCR) did not change compared with the intact age-matched controls. In 15-month-old rats with HF, there was a significant decrease in RC of cardiomyocytes (CM) compared with the intact animals of this age and 2-month-old rats with HF. An age-dependent decrease in the microviscosity of CM membranes in the areas of lipid – lipid interactions and no significant changes in the parameter at the sites of protein – lipid interactions were noted. In 2-month-old animals with HF, the microviscosity of CM membranes in the areas of protein – lipid interactions significantly decreased, and in 15-month-old rats it increased, compared with the intact controls. When carrying out an intergroup comparison, an age-dependent increase in the microviscosity of CM membranes in the areas of protein – lipid interactions and no differences in the parameter in the areas of lipid – lipid interactions were revealed.Conclusion. In the intact rats, the absence of significant changes in respiration with age was revealed. In the 15-month-old animals with HF, respiration in CM was significantly lower than in the intact controls and 2-monthold animals with HF. These changes may be due to the differences in the membrane microviscosity characteristics in different periods of ontogenesis.