[Repolarization of canine ventricular myocardium under the supraventricular rhythm].

The ventricular myocardium is characterized by heterogeneity of activation-recovery interval durations. The transmural ARI gradients are present in the right ventricular apex (ARIs monotonically decreased as one moved from the endocardium to the epicardium), and in the left ventricular base (repolarization in the subepicardial layers was significantly shorter than that in the midmyo cardial layers whereas subendocardial ARIs did not differ from the others). The repolarization pattern of these myocardial regions is governed by the distribution of ARIs. In the apical left ventricular and basal right ventricular areas, no significant transmural differences in the repolarization durations were found. The repolarization pattern of these myocardial regions is governed by the activation sequence. In the right ventricle, ARIs were significantly longer at the base and shorter at the apex. In contrast, in the left ventricle, the apical ARIs were prolonged whereas the basal ARIs were abbreviated. The apex-to-base sequence of myocardial repolarization seems to depend on apex-to-base gradient of activation-recovery intervals durations.

[Reflection of distribution of the epicardial ventricular potential on the dog body surface during electrical stimulation of the myocardium]. / Otobrazhenie na poverkhnosti tulovishcha sobaki raspredeleniia potentsiala na épikarde zheludochkov pri élektricheskoi stimuliatsii miokarda.

Electrical pacing of the apex, base, and free wall of the heart right and left ventricles, as well as the left ventricle's interventricular septum revealed that localisation of the ectopic focus determined the sequence of ventricular depolarisation, the site formation, and the pathway of displacement of the areas' positive and negative potentials and their extrema on the thoracic surface. Time of the mutual movement (inversion) of positive and negative zones on the body surface was found to depend on the pacing site in the wall of ventricles.

[The role of ketone bodies in the development of postalcoholic-intoxication heart damage in rats]. / Issledovanie roli ketonovykh tel v razvitii postintoksikatsionnogo alkogol'nogo povrezhdeniia serdtsa u krys.

Experiments on rats subjected to forced alcoholization for 5.5 days were made to measure the content of ethanol, acetaldehyde and ketone bodies in the blood during intoxication and 2 days after ethanol withdrawal and to estimate the intensity of postintoxication disorders in heart activity on the third day after alcoholization withdrawal. A positive correlation was discovered between depression of left ventricular contractility and the blood content of acetaldehyde and ketone bodies. The magnitude of the threshold of heart fibrillation did not correlate well with the concentration of ethanol during alcoholization. However, it agreed well with ethanol concentration in the postintoxication period. Additional administration to the animals of beta-hydroxybutyrate or caprylic acid in the postintoxication period intensified heart contractility depression. The conclusion is drawn that elimination of ketosis in ethanol withdrawal as well as a progressive taking out of alcoholic patients from dipsomania can prevent the development or attenuate the intensity of postintoxication heart injury.

[The relation of abstinence analgesia to the development of cardiac disorders in the ethanol withdrawal syndrome in rats]. / Sviaz' abstinentnoi anal'gezii s razvitiem kardial'nykh narushenii pri sindrome otmena étanola u krys.

Ethanol was administrated intragastrically (25%, w/v) to Wistar male rats. They received 7-10 g ethanol/kg b.wt. daily in 2 fractional doses for 6 days. In 20-24 hours after the last ethanol administration behavioral and neurological signs of withdrawal syndrome and pain latent period were measured. Analgesia was determined using the tail flick and hot plate tests. Two days later systolic function of the isolated perfusing heart and creatine phosphokinase outflow were examined. Rats had longer latent pain period than in control. Heart perfusion revealed a decrease of systolic pressure, dp/dt of systolic and diastolic pressure, increase of enzyme outflow. Kendall's correlation analysis revealed a positive relationship between intensity of withdrawal symptoms and analgesia index in the hot plate test (tau = +0.343, p. 0.01) and a lack of relationship in the tail flick test. There was negative relationship between the analgesia index and the indices of heart disorders. It is proposed that analgesia index can be used as a predictor of the cardiac muscle injury caused by the alcoholic abstinent syndrome.

[Myocardial damage and the sympatho-adrenal system in ethanol abstinence syndrome in rats]. / Povrezhdenie miokarda i simpatiko-adrenalovaia sistema pri sindrome otmeny étanola u krys.

Increase in content of II-oxycorticosteroids and in activity of dopamine-beta-hydroxylase in blood serum, decrease in concentration of adrenaline in adrenal glands with simultaneous accumulation of the catecholamine in myocardium were observed in rats after intensive alcoholization within 5 days (intragastric administration of ethanol 4-5 g/kg twice daily). In this case content of noradrenaline and its density in the catecholamine-containing nervous fibers were decreased. Ethanol abolishing, as shown by dynamics of catecholamines in heart and adrenal glands, caused an additive stimulation of the sympathoadrenal system, which reached the maximal level within a day and accomplished within 3 days after the last ethanol injection. Abolishing of ethanol led to an increase in the rate of creatine kinase elimination from isolated perfused heart and to activation of the enzyme in rat blood, which reached the maximal value within 3-7 days after the last injection of ethanol. Development of myocardium impairments correlated with accumulation of catecholamines in extraneuronal structures of heart tissue.

[Ethanol withdrawal syndrome in the pathogenesis of alcoholic heart damage]. / Sindrom otmeny étanola v patogeneze alkogo'lnogo porazheniia serdtsa.

In an ultrastructural and functional study of rat hearts, some animals had received liquid food containing ethanol (36.1% of total caloric intake) for 14 weeks (group 1); in half of the rats (group 2), ethanol-containing diet was at regular intervals replaced by an alcohol-free diet (five three-day cycles). Animals on dry forage and water or ethanol-free liquid diet were taken as controls. The study has suggested that recurrent ethanol abstinence syndrome may be a leading pathogenetic factor of alcoholic heart damage.

[Pharmacologic analysis of the role of catecholamines in the mechanism of alcoholic affection of the heart]. / Farmakologicheskii analiz roli katekholaminov v mekhanizme alkogol'nogo porazheniia serdtsa.

The authors studied the effect of 6-oxidopamine and rausedyl on the manifestation of cardiac disorders in rats given 3-5 g/kg ethanol by way of the stomach at 12-hour intervals for 5.5 days. 6-oxidopamine was injected intraperitoneally in a dose of 50 mg/kg 24 hours before the beginning of alcoholization and one hour after the first administration of ethanol. Rausedyl was given in a dose of 0.5 mg/kg by the intragastric route once a day during alcoholization. It was established in perfusion of an isolated rat heart that ethanol induces decrease of cardiac rhythm and rate of relaxation of the heart and coronary duct, increase of systolic and diastolic pressure in the left ventricle, and escape of creatine phosphokinase from the heart. 6-oxidopamine fails to influence while rausedyl weakens the effect of ethanol on heart contractility. Both compounds reduce the escape of creatine phosphokinase from the heart approximately by 40%. It is concluded that the destructive effect of ethanol on the cardiomyocytes is mediated partly by catecholamines. The authors suggest that the cardiotoxic effect of catecholamines in alcoholic intoxication is realized not fully because ethanol weakens their negative action on the heart.

[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.

[Cardiac effects of insulin in ethanol intoxication and in the postintoxication period]. / Kardial'nye éffekty insulina pri intoksikatsii étanolom i v postintoksikatsionnyi period.

Insulin (2 IU/ml) effect on the contractile function, glucose consumption and lactate release by the myocardium was studied in experiments on the isolated rat heart performed at different time after a single (8 g/kg) and 10-fold with a 12-hour interval (8-10 g/kg) intragastric administration of ethanol. A single administration of ethanol failed to influence the contractile function, glucose consumption and lactate release by the isolated heart. The magnitude of a positive inotropic reaction to insulin increased and its stimulating effect on glucose utilization by the myocardium weakened. The reaction of ethanol withdrawal developing after its 10-fold administration led to a disturbance of the contractile and rhythmic functions of the heart and activation of glycolysis. The heart inotropic reaction to insulin in this period weakened and glucose consumption and lactate release stimulated by insulin did not differ from control. During perfusion of intact rat hearts with and without glucose insulin (2 IU/ml) weakened the cardiodepressive effect of ethanol (200 mM).

[Contractile function, glucose consumption and lactate release by the isolated rat heart during different regimens of alcohol administration and after discontinuation of ethanol]. / Sokratitel'naia funktsiia, potreblenie gliukozy i vysvobozhdenie laktata izolirovannym serdtsem krys pri raznykh rezhimakh alkogolizatsii zhivotnykh i posle otmeny étanola.

Acute or chronic intoxication of rats with ethanol (intragastric administration at a dose of 8 g/kg or free-choice drinking of 10% ethanol for 3 months) produced no significant changes in contractile function, glycogen content, glucose uptake and lactate release in isolated hearts. Withdrawal syndrome simulated in rats following a short period of severe intoxication with ethanol at a dose of 4-5 g/kg twice daily has demonstrated a 15 and 28% decrease in peak systolic pressure and tension time index, respectively. In this case glucose uptake and lactate release were 2 times higher. Changes in glycogen level were observed three days after the last ethanol administration. The rats, survived after the abstinence period, revealed areas of perivascular myocardial necrosis. It is concluded that withdrawal syndrome plays an important role in pathogenesis of alcoholic cardiomyopathy.