Фармакокинетика и Фармакодинамика (Nov 2023)

Study of the relationship between the severity of alcoholic cardiomyopathy and the level of alcohol consumption in male and female rats in the model of “home drinking”

  • S. A. Kryzhanovskii,
  • I. B. Tsorin,
  • E. O. Ionova,
  • V. V. Barchukov,
  • V. N. Stolyaruk,
  • M. B. Vititnova,
  • L. G. Kolik,
  • A. D. Durnev

DOI
https://doi.org/10.37489/2587-7836-2023-3-82-93
Journal volume & issue
Vol. 0, no. 3
pp. 82 – 93

Abstract

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Background. Earlier, on the translational model of alcoholic cardiomyopathy (ACMP) developed by us in outbred white rats, which reproduces the main clinical diagnostic signs of this disease, it was shown that in rats of both sexes under conditions of constant 24/7 alcoholization for 24 weeks, AСMP is formed.This study purpose is a comparative assessment of the features of the ACM formation in male and female rats depending on the level of ethanol consumption in model experiments simulating "domestic drunkenness" with periodic alcoholization 24/2 for 24 weeks.Materials and methods. Experiments were performed on outbred white rats randomized into 4 groups: group 1 — control male rats (n=18), group 2 — control female rats (n = 18), group 3 — alcoholized male rats (n = 39) and group 4 — alcoholized female rats (n = 19). Control animals received a normal diet and free access to water. Animals of the 3rd and 4th groups weekly, for 24 weeks, from Friday 22.00 to Monday 8.00, received a 10 % ethanol solution as the only source of liquid with unlimited access to standard food, and the usual diet on the remaining days.Results. In animals of both sexes, after 24 weeks from the consumption start of the ethanol solution, ACM is formed, as evidenced by an increase in the end-systolic and end-diastolic sizes of the left ventricle of the heart (p = 0.0001) and a decrease in its ejection fraction (p = 0.0001), while the degree of pathological myocardial remodeling is more pronounced in females. According to cluster analysis, by the consumption of ethanol (CET), animals of both sexes are divided into 3 subgroups: low, medium and high CET, however, in males, the subgroup with an average CET prevails — 56 %, and in females with a high CET — 47 % (p = 0.0286), the low CET subgroup is minimal (16 %). At the same time, if in males in all subgroups, starting from the 8th week of alcoholization, CET dynamically decreases, then how in females in subgroups with medium and high CET, starting from the 16th week, it increases. It was found that the degree of left ventricular remodeling in females with high and moderate CET was almost 2 times higher than in males (p < 0.05).Conclusion. In model experiments imitating “domestic drunkenness”, it was shown that in females the intensity of the left ventricle heart remodeling is significantly higher than in males, which, apparently, is determined by the identified gender-dependent multidirectional trends in the formation of alcoholic behavior characterized by dynamic growth. consumption of ethanol in female rats as the duration of alcoholization increases.

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