[Determination of the leading factors in the pathogenesis of an alcoholic lesion of the heart]. / Opredelenie vedushchikh faktorov v patogeneze alkogol'nogo porazheniia serdtsa.

Male rats were given per os 25% ethanol solution twice a day at 9.00 and 21.00 for 5.5 consecutive days. Every single dose was 2 to 5 g/kg 2 and 12 hours after 8th gavage ethanol, acetaldehyde and acetone concentrations were measured in blood, 2-8 hours after the last (11th) gavage isolated hearts were perfused by Krebs-Henseleit solution. Applying of Spearman rank correlation method demonstrated negative correlation between mean acetaldehyde concentration and maximal systolic pressure, tension-time index of left ventricle and velocity of contraction and relaxation. Negative correlation has been shown between maximal ethanol concentration (MEC) and rate heart whereas positive correlation has been noticed between MEC and leakage of creatine phosphokinase.

Morphofunctional examination of the heart in rats with the alcohol withdrawal syndrome.

Using histochemical methods, light and electron microscopy, authors examined rat heart 2-6 hours, 1, 3, and 7 days after discontinuation of forced intoxication with alcohol. At the same time, they assessed the contractile function and creatine phosphokinase (CPK) activity in the isolated perfused heart, and the development of animal destruction. Ethanol withdrawal was followed by escalation of vascular disorders in the heart, dystrophic changes in the subcellular structures, considerable polymorphism in enzyme distribution and activity, and formation of foci containing disintegrating myocytes with contractures. The contractile function was impaired and CPK release increased in the isolated heart. The changes were most marked 3 days after ethanol discontinuation to disappear after 7 days. Two to seven days after ethanol cessation, 13.1% of rats perished. Cardiac injury due to alcohol withdrawal syndrome may be one of the factors leading to the development of alcohol cardiomyopathy and a cause of sudden death in patients with documented alcohol abuse.

[Participation of catecholamines in the mechanism of heart damage during the alcohol withdrawal syndrome in rats]. / Uchastie katekholaminov v mekhanizme povrezhdeniia serdtsa pri sindrome otmeny étanola u krys.

Withdrawal syndrome in rats was induced after ethanol administration in a dose of 4-5 g/kg b. w. twice daily for 5 consecutive days. Creatine phosphokinase and lactate dehydrogenase release from the isolated heart and catecholamine distribution in the heart have been investigated in rats suffering from alcohol withdrawal syndrome. Maximum rate of enzyme release was observed on the third day of withdrawal. The density of catecholamine neurons in intact hearts and the hearts of rats sacrificed 2-6 hours, 1, 3, and 7 days after the last ethanol administration was 86, 64, 28, 7 and 38%, respectively. The area of extraneuronal catecholamine distribution accounted for 2, 19, 46, 82 and 4%. Synchronous changes observed in catecholamine distribution and the rate of enzyme release suggest that catecholamines act as a trigger of heart damage in rats with alcohol withdrawal syndrome.

[Comparative characteristics of voluntary and semivoluntary methods of the alcoholization of rats]. / Sravnitel'naia kharakteristika dobrovol'nykh i poludobrovol'nykh metodov alkogolizatsii krys.

Water and ethanol consumption, blood and urine ethanol concentrations were measured in male rats aged 1.5 to 8 months. The animals had ethanol solutions (5-25%) and water as alternate fluid (two-bottle choice) or a 10% ethanol solution as a sole water source. In both cases, the rats did not exceed 7 g/kg of ethanol consumption per day. From 10 a.m. to 16 p.m. the blood ethanol concentration was no more than 0.1 g/l. Ethanol excretion with urine did not go beyond 0.1% of the daily dose. Ethanol consumption was increased by 1-2 g/kg a day if saccharin (0.125%) and sodium chloride (1%) were added to ethanol solution. In this case the withdrawal signs developed after ethanol consumption cessation.

[Alcoholic lesions of the brain]. / Alkogol'nye porazheniia golovnogo mozga.

Brains of 117 alcoholics admitted in the state of alcoholic coma or abstinence syndrome with an increase of blood pressure or development of acute psychosis were studied. The changes in the human brain were compared with those occurring in the brains of 30 rats with chronic alcoholic intoxication and formation of withdrawal syndrome. It is shown that in alcoholic coma and different manifestations of abstinence syndrome vascular and cellular changes take place, that can be attributed to the action of ethanol or its metabolites, as well as catecholamines. In the brain of the animals studied the same cellular and vascular changes were found as in the mentioned alcohol-induced manifestations in man. Progression of cephalic changes due to withdrawal syndrome is associated with more marked structural changes of the hemato-encephalic barrier.

[Catecholamines in the mechanism of the cardionecrotic action of acetaldehyde]. / Katekholaminy v mekhanizme kardionekroticheskogo deistviia atsetal'degida.

Administration of acetaldehyde to rats by inhalation or intraperitoneally (in repeated doses) provokes an emergence of micronecroses in the myocardium. Administration of acetaldehyde in a dose causing no injury to the myocytes potentiates the cardionecrotic action of adrenalin. Pretreatment with L-DOPA potentiates while that of L-alpha-methyl-DOPA or alpha-methyl-p-tyrosine averts the necrosogenous action of acetaldehyde. Under isolated heart perfusion, acetaldehyde administered in the concentrations that exceeded 2-fold and more those in the blood in experiments in vivo had no necrosogenous action. The degree of the adrenalin-induced lesions of the isolated myocardium remained unchanged in the presence of acetaldehyde. It is assumed that the cardionecrotic effect of acetaldehyde is mediated by catecholamines and is effected by stimulation of biogenic amine release from neurons and chromaffin tissue, and is not linked with direct acetaldehyde effect on the realization of the alterative action of catecholamines.

[Myocardium in acute and chronic experimental alcoholic intoxication]. / Miokard pri ostroi i khronicheskoi alkogol'noi intoksikatsii v éksperimente.

The myocardium of both heart ventricles in acute (AAP) and chronic (CAP) alcoholic poisoning was studied in 90 randombred rats. Functional-morphological changes typical of alcoholic cardiomyodystrophy were shown to develop in the heart in AAP and CAP. In AAP, alcoholic cardiomyodystrophy may lead to acute cardiac insufficiency and in CAP to progressive reduction of the contractile function of the heart and disturbances of conductivity in it. In AAP, however, the leading factor is the disturbance of bioenergetics as a result of toxic effect of ethanol and its metabolites on mitochondrial membranes under conditions of markedly disordered microcirculation. In CAP, along disordered microcirculation. In CAP, along with compensatory-adaptative processes in cardiomyocytes there increase the defects of the contractile apparatus, and diffuse fine-focal cardiosclerosis. This is the result of a long-term effect of ethanol and progressive hypoxia due to the affected vessels and disorders in lipid metabolism. Disorders in the function of sarcoplasmic reticulum may contribute to reduced contractile capacity of the heart.

[Pharmacology of several aromatic amino acid decarboxylase inhibitors]. / K farmakologii nekotorykh ingibitorov dekarboksilazy aromaticheskikh aminokislot.

D,L-beta-(3,4-dihydroxyphenyl)lactic acid (I), D,L-beta-(5-hydroxyindolyl-3)lactic acid (II), and L-alpha-methyl-DOPA (III) inhibited the aromatic amino acid decarboxylase (AAAD) competitively. In difference from the compound III, I and II were not AAAD substrates. Compound II selectively suppressed decarboxylation of L-5-hydroxytryptophane. Compounds I and III potentiated the excitation caused in mice by L-DOPA and failed to influence the excitation due to L-5-hudroxytryptophane (L-5-HTP). Compound II attenuated the excitation caused by L-DOPA and L-5-HTP. Pyridoxine hydrochloride and pyridoxalphosphate attenated the excitation caused by L-DOPA and L-5-HTP. Compounds I and III eliminated this action of vitamins B6.

[The pharmacology of 3,4-dihydroxyphenyl-alpha-hydroxypropionic acid sodium salt]. / K farmakologii natrievoi soli 3,4-dioksifenil-al'fa-oksiproiolionovoi kisloty.

Sodium salt of 3,4-dihydroxyphenyl-alpha-hydroxypropionic acid inhibits exploratory behavior and induces hypothermia in mice. The compound enhances central effects of L-DOPA, such as: gross excitation in group, fighting behavior, anticataleptogenic action and hyperthermic effect. The L-DOPA central effects are mitigated by pyridoxal phosphate. The 3,4-dihydroxyphenyl-alpha-hydroxypropionic acid sodium salt abolishes the protective action of pyridoxal phosphate. In vitro this salt inhibits DOPA-decarboxylase. It is suggested that the compound under discussion is a competitive antagonist of L-DOPA, when the latter is involved in reactions with pyridoxal phosphate.

[Facilitation of the effects of L-DOPA by alpha-methyldopa]. / Ob usilenii éffektov L-dopa na fone alpha-metil-DOFA

Alpha-methyl-DOPA increased the duration of excitation induced by L-DOPA in mice, alpha-methyl-DOPA potentiated the anticataleptogenic activity of L-DOPA in mice pretreated with reserpine or haloperidol. Alpha-methyl-DOPA given to cats 30 min prior to L-DOPA diminished the influence of L-DOPA on the blood pressure and the contraction of the nictitating membrane. When given 4 to 6 hours prior to L-DOPA alpha-methyl DOPA enhanced the reaction of the blood pressure and contraction of the nictitating membrane induced by L-DOPA or dopamine.