Beclin-1-Dependent Autophagy of Left Ventricular Cardiomyocytes in SHR and Wistar-Kyoto Rats with Type 1 Diabetes Mellitus.

Autophagy is considered as a mechanism of progression of heart failure, but under certain conditions, it can also act as an adaptation mechanism. Beclin-1 plays the key role in autophagy. We studied the features of Beclin-1 expression in cardiomyocytes of the left ventricle in arterial hypertension, type 1 diabetes mellitus, and their combination. The experiment was performed on male 38-week-old Wistar Kyoto rats and SHR rats aged 38 and 57 weeks. Type 1 diabetes mellitus was modeled by a single parenteral administration of streptozotocin. Expression of Beclin-1 in cardiomyocytes of the left ventricle was evaluated by immunohistochemical analysis. In arterial hypertension, a decrease in the intensity of Beclin-1-dependent autophagy of cardiomyocytes was seen, while in combined pathology, we observed an opposite effect manifested as a significant increase in the expression of protein Beclin-1.

Bright Light Therapy Increases Blood Pressure and Changes the Structure of Circadian Rhythm of Melatonin Secretion in Spontaneously Hypertensive Rats.

Phototherapy (therapy with bright light) is widely used to treat seasonal affective disorders, different types of depression, sleep disorders, and other diseases; it has no significant contraindications, but its effects on functional state and biological rhythms of the cardiovascular system in hypertension are poorly studied. In experiments on Wistar-Kyoto and SHR (spontaneously hypertensive rats) rats, the effect of bright light therapy on the daily profile of BP, HR, and production of epiphyseal melatonin was investigated. Phototherapy was simulated by exposure to 9000-lux cold light at the level animal eyes over 1 h (from 10.00 to 11.00 h) with LED lamps. In freely moving rats (free access to food), daily profiles of BP and HR were studied by 24-h continuous telemetry monitoring. The production of epiphyseal melatonin was assessed by measuring urinary concentration of its stable metabolite 6-sulfatoxymelatonin (aMT6s) during the day and night. During phototherapy, systolic BP significantly increased in in animals of both lines and diastolic BP increased in SHR rats. This effect persisted after the end of phototherapy session. Bright light had no effect on HR. In Wistar-Kyoto rats, phototherapy induced a significant decrease in daily concentration of aMT6s, but its nocturnal level did not change. In SHR rats, bright light therapy significantly decreased nighttime concentration of aMT6s in the urine and had no effect on daytime concentration of this metabolite. As a result, the difference between the night and day levels of aMT6s in the urine was leveled. Phototherapy produced more pronounced and less favorable effect on animals with primary arterial hypertension.

24-Hour Profile of Blood Pressure, Heart Rate, Excretion of Electrolytes, and Locomotor Activity in Wistar-Kyoto and SHR Rats Under Conditions of Free-Run Rhythm.

We presented the results of our study of chronostructure of BP, HR, electrolyte excretion, and locomotor activity under conditions of "free-run rhythm" (light deprivation). In adult male Wistar-Kyoto (normotensive) and SHR (spontaneously hypertensive) rats, BP, biopotentials of the heart (ECG), and locomotor activity were recorded over 24 h by telemetric monitoring and the rate of excretion of electrolytes (Na+, K+, Ca2+, and Mg2+) during the nighttime and daytime hours was measured. It was found that under free-run rhythm, 24-h profiles of BP, HR, excretory function of the kidneys, and locomotor activity underwent more considerable changes in normotensive Wistar-Kyoto rats in comparison with hypertensive SHR rats. However, hypertensive rats demonstrated pronounced changes in rhythmic characteristics of HR, which can restrict adaptation reserves of the cardiovascular system.

Influence of geomagnetic activity and earth weather changes on heart rate and blood pressure in young and healthy population.

There are many references in the literature related to connection between the space weather and the state of human organism. The search of external factors influence on humans is a multi-factor problem and it is well known that humans have a meteo-sensitivity. A direct problem of finding the earth weather conditions, under which the space weather manifests itself most strongly, is discussed in the present work for the first time in the helio-biology. From a formal point of view, this problem requires identification of subset (magnetobiotropic region) in three-dimensional earth's weather parameters such as pressure, temperature, and humidity, corresponding to the days when the human body is the most sensitive to changes in the geomagnetic field variations and when it reacts by statistically significant increase (or decrease) of a particular physiological parameter. This formulation defines the optimization of the problem, and the solution of the latter is not possible without the involvement of powerful metaheuristic methods of searching. Using the algorithm of differential evolution, we prove the existence of magnetobiotropic regions in the earth's weather parameters, which exhibit magneto-sensitivity of systolic, diastolic blood pressure, and heart rate of healthy young subjects for three weather areas (combinations of atmospheric temperature, pressure, and humidity). The maximum value of the correlation confidence for the measurements attributable to the days of the weather conditions that fall into each of three magnetobiotropic areas is an order of 0.006, that is almost 10 times less than the confidence, equal to 0.05, accepted in many helio-biological researches.

Energy deficit as a possible factor for the induction of caspase-dependent apoptosis in left ventricular myocardial cells during genetically determined and secondary arterial hypertension.

Activities of caspase-3 and caspase-8 in the left ventricular myocardium of Chinchilla rabbits with renovascular arterial hypertension and spontaneously hypertensive rats were measured after 10-day administration of a macroergic compound phosphocreatine. Treatment with phosphocreatine prevented activation of caspase-3, but had no effect on caspase-8 during secondary and genetically determined arterial hypertension. Our results indicate that the intrinsic mechanism of the induction of the caspase cascade in myocardial cells dominates over the extrinsic pathway during both types of arterial hypertension. Energy deficit is one of the inducing factors of these processes.

Contractile function of the heart and the state of some stages of lipid metabolism during acute diphtheritic intoxication.

Acute diphtheritic intoxication was modeled in rabbits by intravenous administration of native diphtherin (0.3 minimal lethal dose per 1 kg body weight). The contractile function of the left and right ventricles (peak systolic pressure under conditions of basal hemodynamics and during 5-sec occlusion of the aorta and pulmonary artery, respectively) was estimated 1, 3 and 5 days after the start of the pathological process, the intensity of lipid peroxidation was evaluated by measuring the content of TBA- reactive products in the myocardium. Impairment of the contractile function of both ventricles was observed in the course of intoxication. The level of TBA-reactive products in the left ventricle significantly decreased on day 1, but then returned to normal. Thus, impairment of the contractile function of the left ventricle at the early stages of diphtheritic intoxication is not mediated by activation of lipid peroxidation in cardiomyocytes.

[Effect of hyperbaric oxygenation on paramagnetic centers in the rabbit myocardium during experimental myocardial infarction]. / Vliianie giperbaricheskoi oksigenatsii na paramagnitnye tsentry v myshtse serdtsa krolika pri éksperimental'nom infarkte miokarda.

Changes in paramagnetic centres (PC) concentration in rabbit's myocardial muscle were studied under experimental myocardial infarction during 168 hours by means of ESR-spectroscopy. PC characterized by ESR signal with g = 3.0 was found. It was shown that hyperbaric oxygenation did not affect PC content in the infarction zone, and resulted in an increase of PC concentration with g = 1.94 and g = 2.0 in the intact myocardial zone.

[Changes in the contractile myocardium in acute rhythm disorders]. / Izmeneniia sokratitel'nogo miokarda pri ostrykh narusheniiakh serdechnogo ritma.

Experiments in rabbits were carried out to study the morphology of contractile myocardium in arrhythmias caused by electric stimulation of previously intact myocardium (1st group) and in those caused by inhalation of ammonia steam against the background of exogenous poisoning with barium chloride (2nd group). Morphological lesions of contractile myocardium consisting in granular an vacuolar dystrophy at 1--3 days of the experiment and focal myocytolysis at 7 days were demonstrated. In animals of the 2nd group, morphological lesions in the myocardium were more severe and by the 7th day of the experiment included both focal myocytolysis and contracture alterations. Changes in the blood vessels of the microcirculation bed were similar in both groups consisting of vascular spasm followed by paresis, plethora, diapedetic hemorrhages and early signs of thrombus formation. The latter was observed earlier in animals of the 2nd group. The observed morphological changes in contractile myocardium may be regarded as one of the forms on non-coronarogenic myocardiopathies.

[Patholphysiological aspects of hyperbaric oxygenation exposure on the heart in compensatory hypertrophy]. / Nekotorye patofiziologicheskie aspekty vozdeistviia giperbaricheskoi oksigenatsii na serdtse pri ego kompensatornoi gipertrofii.

Chronic interrupted effect of hyperbaric oxygenation applied for 4 weeks reduces the rate of the development of myocardial hypertrophy in rabbits and is thus conducive to stabilization of myocardial contractile function on a sufficiently high level and increases the reliability of the circulation system in emergency situations. In the dangerous stage of compensatory cardiac hyperfunctions, hyperbaric oxygenation protects the myocardium from destructive changes and activates bionergetic processes, whereas in the stage of marked hypertrophy it inhibits the development of cardiosclerosis. Hyperbaric oxygenation prevents the development of functional isolation of the hypertrophied myocardium from the neurohormonal effects and contributes to the preservation of the reserve capacity of the neuroeffector mechanisms of heart regulations.

[Effect of large doses of nicotinic acid on certain metabolic processes and contractile function of an intact heart]. / Vliianie bol'shikh doz nikotinovoi kisloty na nekotorye obmennye protsessy i sokratitel'nuiu funktsiiu intaktnogo serdtsa

Peroral administration of nicotinic acid to rabbits in amounts of 500 mg, twice a day for 7 days was attended by a reduced contractility of the myocardium, an increased content of catecholamines in the heart and deranged lipids metabolism in the heart muscle. It is assumed that the contractility of the heart is largely determined by the state of the lipids metabolism and their utilization in the generation of energy.

[Effect of combined use of hyperbaric oxygenation and alpha-tocopherol on the contractile function and various components of the antioxidant system of the heart after adrenaline lesioning]. / Vliianie sovmestnogo ispol'zovaniia giperbaricheskoi oksigenatsii i alpha-tokoferola na sokratitel'nuiu funktsiiu i nekotorye komponenty antiokislitel'noi sistemy serdtsa pri ego adrenalinovom povrezhdenii.

A session of hyperbaric oxygenation (HBO) at 2.5 at. abs. conducted for one hour in rabbits with adrenalin heart affection (AHA) immediately after adrenalin administration prevented a decrease in the cardiac contractile function usually developing within two hours after AHA. On the third day of the follow up, rabbits with AHA receiving daily HBO displayed a decrease in the pump and contractile functions as well as in superoxide dismutase (SOD) activity and the antioxidant activity (AOA) of the left ventricle lipids. Combination of HBO sessions with the intra-muscular administration of alpha-tocopherol (50 mg/kg) made the decrease in SOD activity less pronounced and prevented both the fall in lipid AOA and the depression of the heart contractile and pump functions on the third day following AHA. It is suggested that the combined use of HBO and substances increasing the potency of the cell antioxidation system may become one of the principles of reducing HBO side effects and of expanding the potentialities of HBO in treating ischemic and adrenergic heart impairments.

[Myocardial morphology in fibrillation and defibrillation of the heart ventricles]. / Morfologiia miokarda pri fibrilliatsii i defibrilliatsii zheludochkov serdtsa.

The morphology of the contractile myocardium was studied experimentally in fibrillation and defibrillation of the ventricles on 30 rabbits. Morphology of the contractile myocardium appears as vacuolated dystrophy of the cardiomyocytes, destruction of mitochondria and contracture lesions of the myofibrils. The latter with progressing fibrillation become irreversible. Myocardial changes are related both to the mechanical lesions of cardiomyocytes and the haemodynamic disorders, developing as a result of ventricular fibrillation, which leads to marked myocardial hypoxia. The changes in the microcirculatory bed contribute to the development of the latter. Hyperfunction of the intracellular structures, especially of mitochondria and myofibrils, taking place under unfavourable conditions leads to a rapid energy depletion, which is one of the main causes of development of the acute cardiac insufficiency in this type of arrhythmias. Studies of cardiac defibrillation enabled one to elicit the dynamics of morphological changes, appearing in the myocardium as related to the duration of ventricular fibrillation.

[Soluble guanyl cyclase of blood platelets and heart of rats with experimental myocardial ischemia]. / Rastvorimaia guanilattsiklaza trombotsitov i serdtsa krysy pri éksperimental'noi ishemii miokarda.

The activity of soluble guanylate cyclase (GC) and its regulation in the platelets and heart of normal rats and rats with experimental acute myocardial ischemia provoked by coronary ligation was examined. There was a synchronous reduction in platelet and heart GC activity immediately following 15 minutes after surgery along with a drastically marked drop in genuine baseline activity (with Mg2+) to 19 and 40% in the platelets and heart (both ischemic and intact areas), respectively. Following 24 hours, GC activity insignificantly rose (up to 35.5%) in the platelets with Mg2+, that with Mn2+ remained unchanged; in the ischemic area it decreased much more (to 30%), whereas in the intact area it partially restored (up to 70%). The stimulating effect of DTT on platelet GC activity 15 minutes after the surgery drastically rose (from 2.8 to 8), then returning to normal 24 hours later. The findings show an enhancement in free radical processes typical of ischemia and indicate their high response of platelet GC at the earliest stages. Sodium nitroprusside-induced activation of myocardial GC diminished in the ischemic area in 15 minutes and virtually lacked in 24 hours. There was a less pronounced decrease in GC activation in the intact area. It is suggested that lower enzymatic activatibility is associated with heme loss. The absence of sodium nitroprusside-induced stimulation of platelet GC both in health and in the abnormality under question may be due to primary heme enzymatic deficiency.

[Effect of baxacor on the hemodynamics and contractile function of the myocardium in acute ischemia (an experimental study)]. / Vliianie baksakora na gemodinamiku i sokratitel'nuiu funktsiiu miokarda pri ostroi ego ishemii (éksperimental'noe issledovanie).

The article discusses the results of experiments on 16 dogs in which acute myocardial ischemia was reproduced with intravenous infusion of baksacor and without the infusion of the drug; control experiments were also performed on an intact heart with baksacor infusion. Hemodynamics and myocardial contractility were studied throughout the entire experiment. It was found that baksacor had practically no effect on an intact heart. In acute ischemia the maximum effect of the drug was manifested on the 5th-25th minutes. An increase of the stroke volume and normalization of the rate of shortening of the contraction component were observed. An anti-arrhythmic effect of baksacor was noted.

[Effect of large heparin doses on the contractile function, structure and lipid metabolic indices of the myocardium in intact rabbits]. / Vliianie bol'shikh doz geparina na sokratitel'nuiu funktsiiu, strukturu i nekotorye pokazateli lipidnogo obmena miokarda intaktnykh krolikov.

The effect of large doses (700 U/kg daily for 6 days) of heparin on the heart contractile function, myocardial morphology, content of free fatty acids in the blood, and the activity of tri- and monoglycerin lipase in blood plasma and heart tissue of intact rabbits was studied 24, 72 hours and 6 days after the beginning of heparin administration. It was established that the activity of lipolytic enzymes intensified, the concentration of free fatty acids in blood plasma grows, and the myocardial contractility increases after heparin administration. The phase structure of the cardiac cycle is simultaneously disturbed slightly. It is concluded that the intensification of lipolysis plays a role in increasing the myocardial contractility.

[Various characteristics of lipid metabolism in experimental myocardial infarct and their effect on myocardial contraction]. / Nekotorye osobennosti lipidnogo obmena pri éksperimental'nom infarkte miokarda i vliianie ikh na sokratitel'nuiu funktsiiu serdtsa.

It was established in rabbit experiments that in acute focal myocardial ischemia induced by ligation of the descending branch of the left coronary artery, diminution of the force of cardiac contractions and an increase in the content of free fatty acids in blood plasma are observed. Progressing intramyocardial lipolysis is noted for 6 days. Lipolysis blockade with large doses of nicotinic acid leads to an extremely sharp drop in the contractile force of the heart in experimental animals with acute focal myocardial ischemia and to drastic damage of the myocardial ultrastructures as well as to disorders of the metabolism of intracellular lipids.

[Effect of hyperbaric oxygenation on the cyclic nucleotide and catecholamine content, energy and carbohydrate metabolism and on cardiac contractile function in acute focal myocardial ischemia]. / Vliianie giperbaricheskoi oksigenatsii na soderzhanie tsiklicheskikh nukleotidov, katekholaminov, énergeticheskii, uglevodnyi obmen i sokratitel'nuiu funktsiiu sedrtsa pri ostroi ochagovoi ishemii miokarda.

Two hours after the ligation of the descending branch of the left coronary artery in rabbits the contractile function of the heart decreased, concentration of phosphocreatine, ATP, glycogen dropped, and the content of lactic acid in the ischaemic and intact areas of the left ventricle elevated. Two-hour ischaemia of the myocardium was accompanied by increase of the cAMP and decrease of cGMP levels in the ischaemic and intact areas. Hyperbaric oxygenation (HBO, 2 at. abs, 1 h) started 30-40 min after coronary occlusion led to partial restoration of the cardiac contractility function, improvement of the energy and carbohydrate metabolism in the ischaemic and intact areas of the left ventricle and prevented cardiac fibrillation. It is surmised that favourable action of HBO on the functional state of the heart in its acute focal ischaemia is related not only to the antihypoxic effect but also to the rearrangement of the system of neurohormonal control of the heart.

[Effect of hyperbaric oxygenation on animal deaths from acute circulatory disorders caused by intense cerebral excitation]. / Vliianie giperbaricheskoi oksigenatsii na smertnost' zhivotnykh ot ostrykh narushenii krovoobrashcheniia, vyzvannykh rezkim vozbuzhdeniem mozga.

Sound exposure to 100--120 dB caused death of about 6--16% of white rats KM line from the blood circulation disturbances. The hyperbaric oxygenation (2 atm) decreased the death rate among rats of 4 to 15 months old while having no effect upon younger ones (2--4 months old). The rats who died in hyperbaric oxygenation suffered from O2 intoxication more often than those who survived. Administration of caffeine reduced the positive effect of hyperbaric oxygenation.

[Contractile function and antioxidative system of the myocardium of the intact rabbit during hyperbaric oxygenation]. / Sokratitel'naia funktsiia i antiokislitel'naia sistema miokarda intaktnykh krolikov pri giperbaricheskoi oksigenatsii.

Daily exposures of rabbits to the HBO (2 ata, 1 hr) enhanced activity of glutathione-peroxidase for all 28 days of exposure. Other parameters of the antioxidative defence and the contractile function remained unchanged. The 2.5-ata oxygenation sharply reduced the activity of antioxidative enzymes, the antioxidative activity of lipids, and the tissue resistance against the induced peroxide oxidation of lipids. The heart contractile function was obviously worsened. Sites of necrosis appeared in the myocardium tissue. Increase in oxygenation seems to lead to changes of adaptation of the antioxidative system, but the exhaustion of the latter's power reserves potentiates the toxic effect of hyperoxia.

[Changes in the activity of cyclic adenosine monophosphate metabolism enzymes in myocardial hypertrophy and after exposure to hyperbaric oxygenation]. / Izmenenie aktivnosti fermentov obmena tsiklicheskogo adenozinmonofosfata pri gipertrofii miokarda i vozdeistvii giperbaricheskoi oksigenatsii.

Hypertrophy of myocardium, developed within 4 weeks after aorta stenosis, led to alteration in content of adrenaline in heart tissue as well as in some pathways of cAMP turnover: decrease in content of cAMP, an increase in the basal activity of adenylate cyclase, decrease in activation of the enzyme by adrenaline; activity of phosphodiesterase was not distinctly altered. Under conditions of hyperbaric oxygenation hypertrophy of myocardium became less distinct, content of cAMP was increased up to the normal value, the increased basal activity of adenylate cyclase was slightly decreased, whereas sensitivity of the enzyme to adrenaline did not reduce, content of adrenaline was increased.