The dissertation presents a theoretical generalization and a new solution to an important scientific problem, which is to elucidate the pathogenetic features of the development of ethanol damage to the liver and heart in rats with high and low motor activity.
All experiments were carried out on 192 outbred male rats, which were divided into 8 experimental groups: І – control group, ІІ – group of rats, which were given 5% glucose solution to drink during 7 days, ІІІ – group of rats with acute ethanol hepatitis. The rats included into the І-ІІІ groups were 4-4.5 months of age, IV – control group, V – group of rats, which were given 5% glucose solution to drink during 67 days, VI – group of rats with ethanol hepatosis, VII – group of rats with ethanol fibrosis, VIII – group of rats with ethanol cirrhosis. The rats included into the ІV-VІІІ groups were 6-7 months of age.
On the basis of a comprehensive study, it was established pathogenetic features of heart damage in animals with high and low motor activity depending on the manifestations of oxidative stress, the development of endogenous intoxication, inflammation, and dysregulation of the autonomic nervous system.
It was found that acute ethanol hepatitis is accompanied by a severe increasing of the levels of lipid peroxidation products; and in rats with ethanol hepatosis, fibrosis, and cirrhosis of the liver, it was observed the significant increasing of the levels of oxynomodified proteins, which were predominant in rats with high motor activity. It was found for the first time, that liver damage, caused by ethanol in animals is accompanied by a compensatory increasing of antioxidant protection in both the homogenate of the heart and in the blood serum. An increase level of interleukin 1β under the conditions of ethanol hepatitis was found only in rats with low motor activity and with a decreased immune response in the development of hepatosis, fibrosis and cirrhosis of the liver. It was detected that the degree of endogenous intoxication and the severity of multiorgan failure in ethanol-induced liver pathology depend on the motor activity of animals: in animals with high motor activity, in comparison to the rats with low motor activity, under the conditions of ethanol hepatitis the content of medium mass molecules in the blood is higher at λ = 280, in hepatosis – λ = 254, λ = 260, in fibrosis – at λ = 238, λ = 260, λ = 280, in cirrhosis – λ = 254.
The peculiarities of autonomic regulation of heart rhythm under the influence of ethanol and depending on motor activity of animals were established. The sympathetic regulation of heart rate by humoral channels in rats with high motor activity and the tone of the parasympathetic part of the autonomic nervous system in all groups of animals were increased under the conditions of ethanol hepatitis. On the background of ethanol hepatosis, the sympathetic regulation of heart rate by humoral channels in all groups of rats and nerve channels in rats with high motor activity was decreased. Fibrosis and cirrhosis of the liver were accompanied by increasing of sympathetic impacts on the heart through humoral channels in rats with high motor activity, and decreasing of parasympathetic regulation under the conditions of liver fibrosis in animals with low motor activity.
It was established the compensatory changes of the central hemodynamics on the background of chronic ethanol damage, which were more significant in animals with low motor activity: in animals with ethanol hepatosis the peripheral resistance of vessels was decreased; in animals with fibrosis it was also observed the decreasing of peripheral resistance of vessels and venous outflow; in animals with cirrhosis, the intensity of pulse blood supply to the vessels was increased due to the blood output from the left ventricle. It was found that in animals with high motor activity, comparing with those with low motor activity, the morphological damage to the heart and liver was more significant.
