[Synergism of carbamylated darbepoetin and L-ethoxidol in the model of experimental kidney ischemia].

AIM: to determine the efficiency of different doses of erythropoietin and carbamylated darbepoetin, to prove experimentally the possibility of increasing the efficiency of carbamylated darbepoetin when using the levorotatory stereoisomer of ethoxidol. MATERIALS AND METHODS: On the model of ischemia-reperfusion injury in male CD-1 mice that were undergone to contralateral nephrectomy, the nephroprotective effect of different doses of erythropoietin alfa, carbamylated darbepoetin, L-ethoxidol (the levorotatory enantiomer of ethylmethylhydroxypyridine malate), and the combined use of L-ethapylated carboxypyridine malate and L-etapoietin alfa was studied. The parameters of microcirculation and glomerular filtration rate were studied one day after 30-minute ischemia. RESULTS: It has been established that the prophylactic use of erythropoietin alfa and carbamylated darbepoetin in the model of ischemia-reperfusion injury of a single kidney reduces the severity of microcirculatory impairment and ensures the preservation of the glomerular filtration rate in dose-dependent manner. The synergistic effect of L-ethoxidol and carbamylated darbepoetin was found when these substances were used together. CONCLUSION: Prevention of ischemia-reperfusion kidney injury by analogs of human erythropoietin and their combination with ethylmethylhydroxypyridine derivatives is experimentally-proved.

[Antiarrhythmic properties of 2-(2'-hydroxy-2')-substituted ethyl-1,2,3,4-octahydropyrrolo[1,2-a]pyrazines]. / Antiaritmicheskie svoistva 2-(2'-gidroksi-2'-zameshchennykh)-étil-oktagidropirrolo[1,2-a]pirazinov.

The antiarrhythmic activity and acute toxicity of a series of 2-(2'-hydroxy-2')-substituted ethyloctahydropyrrolo[1,2-a]pyrazines were studied. Two most promising compound (PV-238) is characterized by high antiarrhythmic activity, broad spectrum of action, and low toxicity.

[2-(2'-hydroxy 2'-substituted) ethyl-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazines--a novel group of substances with anti-arrhythmia activity]. / 2-(2'-Gidroksi-2'-zameshchennye) étil-1,2,3,4-tetragidropirrolo[1,2-a]piraziny--novaia gruppa veshchestv, obladaiushchikh antiaritmicheskoi aktivnost'iu.

The antiarrhythmic activity and acute toxicity of a series of 2-(2'-hydroxy-2'-substituted) ethyl-1,2,3,4-tetrahydropyrrolo[1,2- a]pyrazines were studied. Two most promising compounds (PV-168 PV-174) are characterized by a high antiarrhythmic activity, a broad spectrum of action, and low toxicity.

[Use of thymogen in the treatment of various forms of acute abdominal disorders in an experiment]. / Primenenie timogena v lechenii nekotorykh vidov ostroi abdominal'noi patologii v éksperimente.

The authors have carried out experimental studies of thymogen action on the course of acute pancreatitis and acute peritonitis in white albino rat males. The preparation was introduced into the abdominal cavity early after the modeling and every 24 hours for 5 days. The results of the trial demonstrate that the degree of autoenzyme aggression (the data of blood serum alpha-amylolytic activity control) and the content of lipid peroxidation products (assessment of malonic dialdehyde quantity in tissue homogenate) were low in the experimental group as compared to the untreated animals. In the experimental group less pronounced depression of antiradical activity (superoxide dismutase and catalase activity control) was found, leukocytosis and leukocyte intoxication index were diminished. Thus, the efficiency of thymogen in acute inflammatory and destructive abdominal diseases has been proved.

[The effect of thymogen on the heart in ischemia and reperfusion]. / Vliianie timogena na sostoianie serdtsa pri ishemii i reperfuzii.

The anti-ischemic properties of thymogen were studied on an isolated heart model. Its cardioprotective effect was higher than that of dalargin and verapamil. The mechanism of the thymogen anti-ischemic action is realized without the participation of the opiate receptors and blockade of calcium entrance into the cardiomyocytes.

[The anti-arrhythmia properties of thymogen]. / Antiaritmicheskie svoistva timogena.

The antiarrhythmic and antifibrillary effects of thymogen were determined by using 6 models of arrhythmias induced by aconitine, calcium chloride, strophanthin, low-sodium, reperfusion, and epinephrine. The dose-response curve was examined. The mechanism of thymogen's action was also studied.

[The effect of a number of pharmacological preparations on Na-H metabolic activity and on the passive permeability for protons of the sarcolemma of the isolated heart]. / Vliianie riada farmakologicheskikh preparatov na aktivnost' Na--H-obmena i passivnuiu pronitsaemost' sarkolemmy izolirobvannogo serdtsa dlia protonov.

The influence of the local anesthetics hydrocortisone hemisuccinate and peptide drugs (thymogen and dalargin) on Na-H exchange activity and passive proton permeability of the sarcolemma was studied in experiments on isolated rat hearts. It was established that neither local anesthetics or hydrocortisone hemisuccinate, nor peptide drugs affected Na-H exchange activity. Lidocaine (5 mM), procaine (5 mM), hydrocortisone hemisuccinate (500-750 mg/l) inhibited sarcolemmal passive proton permeability by 40-70%. Aetaphone in the micromolar range attenuated the role of these effects in the antiarrhythmic action of local anesthetics and aetaphone.

[The effect of dalargin on the course of experimental cardiac arrhythmias]. / Vliianie dalargina na techenie éksperimental'nykh aritmii serdtsa.

Five models of arrhythmias (aconitine-, calcium chloride- and low-sodium-induced models on rats, coronary artery ligation and reperfusion in dogs) were used to study the antiarrhythmic and antifibrillatory effects. The latters were not inferior to those shown by the well-known antiarrhythmics. The mechanisms of the action of dalargin are discussed in the paper.

[Effects of etafon on calcium ion contents in smooth muscle cells of the aorta]. / Vliianie étafona na soderzhanie ionov kal'tsiia v gladkomyshechnykh kletkakh aorty.

Aethaphonium (dialicor) in 5-20 microM concentrations causes the dose dependent Ca decreasing in resting smooth muscle cells of rabbit aorta. In dose of 0.5-2.0 microM dialicor decreases the extent of transient in cytosolic-free calcium induced by application acetylcholine (10 microM) and high extracellular K (119 microM). This effect of dialicor is most expressed in attitude to the myocytes, containing the hyper K medium.

[Specific activity and toxicity of hemostatic feracryl-based plaster]. / Spetsificheskaia aktivnost' i toksichnost' krovoostanavlivaiushchego plastyria na osnove ferakrila.

In experiments on 126 rabbits and 156 guinea pigs, a study was made of specific activity, subacute and chronic toxicity of a new hemostatic feracryl-based plaster. The data obtained indicate a pronounced and stable hemostatic activity of the plaster in different types of wounds demonstrated in two species of animals, including hypocoagulation state. The plaster exerts no local irritative, resorptive toxic effect on tissues and possesses no allergenic properties.

[Action of anti-arrhythmia agents in ischemia and hyperoxia]. / Deistvie nekotorykh protivoaritmicheskikh sredstv v usloviiakh ishemii i giperoksii.

During experiments (128 rabbits) it was shown that under ischemia and hyperoxia the pharmacodynamics of lidocaine, anaprilin and ethacizine changed in centrogenic and peripheral arrhythmias induced by aconitine. Hyperoxia significantly potentiated the antiarrhythmic effect of the drugs except lidocaine action in centrogenic arrhythmias.

[Modeling of myocardial lesions of varying degrees of manifestation]. / Modelirovanie porazhenii miokarda razlichnoi stepeni vyrazhennosti.

Five variants of myocardial lesions of different degree were simulated in experiments on 8 dogs, 61 rabbits and 30 rats, namely micronecrosis, diffuse myocarditis, focal dystrophy, small- and large-focal myocardial infarction. The experimental models of heart lesions can be used for studying the pathophysiological mechanisms in cardiac pathology and evaluation of the therapeutic efficacy of new drugs in experimental pharmacology.

[Quantitative evaluation and prognosis of the biological effects of hyperoxia]. / O kolichestvennoi otsenke i prognozirovanii biologicheskikh éffektov giperoksii.

Experiments in 104 white mice subjected to hyperoxia at different regimens of oxygenation, carried out by means of mathematical modelling of three hyperoxic effects (bradypnea, convulsions, lethality) revealed the dependence of biological (physiological, toxic) effects of hyperoxia upon both components of the oxygenation regimen (oxygen pressure, time of exposure). The proposed concept of integral dose allows to determine pressure-exposure correlations corresponding to a given biological phenomenon and to prognosticate the effects of hyperoxia.

[Metabolic and ultrastructural characteristics of myocardial contraction in experimental small focal myocardial infarction]. / Metabolicheskaia i ul'trastrukturnaia kharakteristika sokratitel'noi funktsii serdtsa pri éksperimental'nom melkoochagovom porazhenii miokarda.

In dogs, pituitrin increases, and isadrin reduces, the tonicity of coronary arteries. Successive administration of the two agents to rabbits causes functional and metabolic unbalance of the heart, with resultant myocardial necrotic foci in the presence of blood hypercoagulation and heart muscle contractility disordered. The disorder of cardiomyocyte stereo architectonics is an essential element of the pathophysiologic mechanism of small-focal myocardial infarction.

[Effect of hyperbaric oxygenation on the oxidative phosphorylation in mitochondria of normal and ischemic myocardium]. / Vliianie giperbaricheskoi oksigenatsii na okislitel'noe fosforilirovanie v mitokhondriiakh normal'nogo i ishemizirovannogo miokarda.

Oxygen, under conditions of elevated pressure 303.975 kPi, was shown to alter oxidative phosphorylation in mitochondria of rabbit heart. Inhibition of oxidative phosphorylation in intact animals and stimulation--in rabbits with myocardial ischemia were observed under conditions of high oxygen pressure. With an increase in frequency of the hyperbaric oxygenation treatments the inhibitory effect if high pressure oxygen was strengthened.