[Effects of anomalous rise of air temperature on population mortality].

Global climate warming for the last 10 years actualized the problem of mortality rise in some European countries in anomalous summer heat. Russia faced this problem in July-August 2010 when extreme heat entailed a significant elevation of mortality in 31 regions of the country primarily due to coronary heart disease and cerebrovascular diseases. The analysis of foreign researches has shown that old age and living in cities are leading risk factors of deat in anomalous heat. Experience of the European countries and USA evidences that stay in conditioned apartments and early referral for medical assistance are most effective death preventive measures in heat.

[The study of hypotensive action of dinitrosyl-iron complex with glutathione containing drug oxacom in healthy volunteers].

On the basis of earlier executed studies of hypotensive effect of dinitrosyl iron complexes (DNIC) with glutathione, the drug has been created in industrial conditions named oxacom. Preliminary pharmacological studies of oxacom have not revealed negative qualities. The drug has been now tested in 14 healthy men in whom at single intravenous introduction it caused typical response - a decrease of diastolic as well as systolic arterial pressure on 24-27 mmHg through 3-4 min with subsequent very slow restoration in 8-10 hours. The heart rate after initial rise was quickly normalized. Echocardiography revealed unaltered cardiac output in spite of reduced cardiac filling by 28%. The multilateral analysis of clinical and biochemical data has revealed an absence of essential alterations which could lead to pathological consequences. The drug is recommended for carrying out of the second phase of clinical trial. The comparative study of the efficiency of hypotensive action of oxacom, S-nitrosoglutathione (GS-NO) and sodium nitrite (NO2) in rats has shown that the duration of effect was the greatest at oxacom action.

[First experience of clinical use of new class III antiarrhythmic agent niferidil in patients with persistent atrial fibrillation and flutter].

The aim of the study was to evaluate the efficacy and safety of administered intravenously niferidil in doses 10, 20 and 30 mkg per kg in patients with persistent atrial fibrillation (AF) and flutter (AFL) for pharmacological cardioversion. The study included 30 patients (22 male) with persistent AF (n = 28) and AFL (n = 2) without structural heart diseases with median arrhythmia duration 6.1 +/- 4.8 months (2 weeks to 24 months). Niferidil was administered as 3 bolus injections (10 mkg per kg each) performed with the interval of 15 minutes. Antiarrhythmic efficacy of niferidil in dose of 10 mkg per kg was 60%, in dose of 20 mkg per kg it was 70%, and in dose of 30 mkg per kg reached 90% prespectively. The part of the patients, in whom QTc prolongation exceeded potentionally dangerous value of 500 mc, was 22.2% (6 of 27). None of the patients developed proarrhythmic side effect as torsade de pointes.

[The influence of chronic neurotization on the monoaminergic systems of various brain structures in rats with various typological characteristics].

Typological behavioral features of Wistar rats were tested in the open field and in Porsolt test. Rats were assigned to groups with high (HAct), medium (MAct), and low (LAct) behavioral activities. The same rats were assigned to high (HDep), medium (MDep) and low depressive (LDep) groups. The release of norepinephrine, dopamine, serotonin and their metabolites in homogenates obtained from the hypothalamus, hippocampus, frontal cortex and amygdala was assessed by microdialysis and HPLC. In these groups, the monoamine concentrations were different: the level of serotonin was higher in the hypothalamus and norepinephrine and 5-HIAA levels were lower in the hippocampus of MAct - MDep rats as compared to LAct - HDep. Chronic neurotization caused changes in monoamine concentrations in the hypothalamus and amygdala in rats of all groups, whereas in the hippocampus and frontal cortex monoamine changes were observed in HAct - LDep and LAct -HDep rats. The most prominent changes in monoamines levels in neurotized rats with different types of behavior were found in the frontal cortex, amygdala and hippocampus. The results show a correlation between the typological of behavioral characteristics and the reaction to stress of monoaminergic systems of the hypothalamus, hippocampus, frontal cortex and amygdala.

[Electrophysiological experimental study of a novel class III antiarrhythmic drug RG-2]. / Eksperimental'noe élektrofiziologicheskoe issledovanie preparata III klassa RG-2.

The electrophysiologic effects of a new drug, RG-2 were studied on anesthetized open-chest dogs and on rabbit right atrial tissue. RG-2 was manufactured in Chemical-Pharmaceutical Institute in Moscow. Dogs (n=12) were anesthetized with sodium pentobarbital (30 mg/kg, i.v.). An ECG lead II, arterial blood pressure, His bundle electrogram, atrial and ventricular bipolar electrograms were continuously monitored, recorded and then analyzed by a computerized complex for electrophysiological study. Electrophysiological variables, ECG parameters, atrioventricular conduction (His electrogram) and blood pressure were determined after sequential i.v. administration of 1, 5, 10, 20, 40 and 80 ug/kg of RG-2. Interval between injections was 60 min. RG-2 had no significant effect on PQ, QRS, S-A, A-H and H-V intervals, but the drug caused dose-dependent increase of R-R and QT intervals. Moreover, RG-2 dose-dependently increased the atrial and ventricular effective refractory periods (AERP and VERP). Maximal increases of AERP and VERP registered at 5 min after administration of RG-2 (40 microg/kg) were 46+/-2% (p<0.001 vs control) and 23+/-6% (p<0.05 vs control), respectively. In the isolated rabbit right atrial tissue RG-2 (0.01 to 1 microM) had no effects on maximal diastolic potential, action potential amplitude and Vmax, but revealed concentration-dependent increase of action potential duration at 90% repolarization level (APD90%). The maximal effects on APD90% obtained after RG superfusion at 1 microM were 26+/-7% (p<0.001 vs control). We conclude that RG-2 has significant effects of class III antiarrhythmic drugs in vivo and in vitro.

[Chronic stress increases the reactivity of central depressor mechanisms]. / Khronicheskii stress uvelichivaet reaktivnost' tsentral'nykh depressornykh mekhanizmov.

The activity of noradrenergic system of lateral hypothalamus and hemodynamics were studied during acute restraint in chronically stressed and control rats. Arterial blood pressure in rest was negatively proportional to basal norepinephrine concentration in dialysate of lateral hypothalamus. Animals with high increase of norepinephrine levels in dialysate during acute stress had rapid return of arterial blood pressure to basal values while stress-induced hypertension in the beginning of restraint was the same as in rats with low increase of norepinephrine levels. Data obtained show the depressor role of noradrenergic system of lateral hypothalamus. The enhanced reactivity of noradrenergic depressor system may be one of the mechanisms providing cardiovascular adaptation to stress.

[The activity of the monoaminergic systems of the rat hypothalamus in acute stress after chronic stressing]. / Aktivnost' monoaminergicheskikh sistem gipotalamusa krys pri ostrom stresse posle khronicheskogo stressirovaniia.

The influence of chronic stress (footshock combined with randomized light flashes) on acute stress-induced (immobilization) release of noradrenaline, dopamine and serotonin in rat lateral hypothalamus was assessed by microdialysis. The chronic stress resulted in an increase and prolongation of the acute stress-induced release of noradrenaline but not of dopamine and serotonin. The increased rate of accumulation of dioxyphenylacetic acid and unchanged accumulation of homovanillic acid (dopamine metabolites) and dopamine during and after the acute stress in chronically stressed animals reflect a rise of synthetic activity of catecholaminergic systems in response to acute stress and reuptake increase. Marked stress-induced increase in hydroxyindoleacetic acid in chronically stressed rats without any changes in the ST dynamics may be regarded in a similar way. A significant increase in potassium-stimulated release of all the studied monoamines was found while their basal level remained unchanged. The conclusions was made that the hyperergic release of neurotransmitters may be the basis of an inadequate response of animals to acute stress, i.e., one of the neurotic symptoms.

[The first original Russian class-III antiarrhythmic nibentan]. / Pervyi original'nyi otechestvennyi antiaritmik III klassa nibentan.

The paper presents experimental and clinical findings of the new antiarrhythmic drug nibentan. The agent was found to be a class-III antiarrhythmic agent in terms of its electrophysiological effects and an inhibitor of the delayed rectifier potassium current in terms of its effects on the ionic channels of cardiomyocytes. The clinical trial of nibentan shows that the drug is highly effective (in 70-100% of cases) in patients with atrial flutter and fibrillation and in those with supraventricular tachycardia and it is less effective in suppressing ventricular premature contractions and tachycardia. The rate of arrhythmogenic effects produced by the drug was inversely related to its antiarrhythmic action. Nibentan has been approved for clinical use.

[New approach to the deposition of biologically active compounds in the body: an experimental study of the intracoronary administration of modified Sephadex]. / Novyi podkhod k deponirovaniiu biologicheski aktivnykh soedinenii v organizme: izuchenie intrakoronarnogo vvedeniia modifitsirovannogo sefadeksa v éksperiemnte.

The possibility of depositing in the myocardium drugs immobilized on modified Sephadex was studied. The method makes it possible to produce optimum local concentration of the drug with a predetermined rate of its detachment and has significant advantages over the commonly used methods for introducing drugs. Appraisal of a complex of data, including the findings of morphologic examination and analysis of the ECG and the curves of changes in the activity of CPK and hypoxanthine, has shown that intracoronary administration of 0.02 mg of Sephadex microspheres (approximately 20 000 microparticles) 20--40 mc in diameter per 1 g of dog myocardium has no harmful microembolic effect.

[The relationship between the pineal gland and the hypothalamo-hypophyseal complex. I. The effect of pinealectomy, binding and continuous illumination on H3-leucine incorporation in the nucleus of the anterior, middle and posterior hypothalamus of prepubertal and sexually mature rats]. / Vzaimosviaz' pineal'noi zhelezy s gipotalamo-gipofizarnym kompleksom. I. Vliianie pinealéktomii, oslepleniia i postoiannogo osveshcheniia na vkliuchenie H3-leitsina v iadra perednego, srednego i zadnego gipotalamusa prepubertatnykh i polovozrelykh krys

Autoradiography was applied to the study of the effect of extirpation of the epiphysis in rats on the level of H3-leucine incorporation by the neurons of 8 couples of the nuclei localized in the anterior, middle and posterior portions of the hypothalamus. Experiments were conducted on female animals of the prepubertal and reproductive age. Pinealectomy was combined with binding (a factor intensifying the physiological status of the epiphysis) and continuous illumination (a factor inhibiting the function of this gland). In the blinded prepubertal rats pinealectomy enhanced the H3-leucine incorporation into the supraoptic nucleus by 38%, into the paraventricular--by 26%, into the dorsomedial--by 61%, into the premammillary dorsal--by 58%, into the ventro-medial--by 40%, into the premammillary ventral--by 36%, and into the anterior hypothalamic--by 26%. In mature rats this index exceeded, after pinealectomy, such in the sham-operated animals (control) in the supraoptic nucleus by 48%, in the paraventral--by 40%, in the premamillary ventral--by 80%, in the arcuate--by 48%, in the premammillary dorsal--by 35%, in the ventro-medial--by 29%, and in the dorso-medial--by 26%. Continuous illumination reduced the stimulating influence of pinealectomy on the H3-leucine incorporation into the neurons of the premammillary and the arcuate nuclei, without changing the difference between the experiment and control in the macrocellular nuclei. On the whole, the results obtained permit a conclusion to be drawn on tonic inhibition by the epiphysis of the extensive hypothalamic zones.

[Interrelationship of the pineal body with the hypothalamo-hypophyseal complex. II. The effect of melatonin on the incorporation of H3-leucine in the anterior and medial hypothalamic nuclei of pinealectomized blinded rats]. / Vzaimosviaz' pineal'noi zhelezy s gipotalamo-gipofizarnym kompleksom. II. Vliianie melatonina na vkliuchenie H3-leitsina v iade perednego i srednego gipotalamusa pinealéktomirovannykh osleplennykh krys

A study was made of the effect of low doses of melatonin on the H3-leucine incorporation into the supraoptic, paraventricular, ventro-medial, and arcuate nuclei of the hypothalamus. Sexually mature blinded pinealectomized female rats were used in these experiments. Melatonin administered in a dose of 10 mug at 11 a.m. for 9 days inhibited the biosynthetic potential of the mentioned hypothalamic nuclei enhanced by extirpation of the epiphysis. Administration of melatonin at 11 p.m. in the same doses produced no effect on leucine incorporation.