The influence of adrenoreactive preparations on clinical and haemodynamic parameters in patients with ischaemic heart disease.

The influence of anaprilin, oxprenolol, nonachlazine, prazosin and levodopa on the clinical course and haemodynamics was investigated in 138 patients with ischaemic heart disease in whom selective coronary angiography had revealed an up to 50 percent stenosis of one of coronary arteries. The clinical picture of IHD patients with a high tolerance of physical exercise was characterized by a preponderance of spontaneous angina pectoris accompanied by painless myocardial ischaemia. A certain role in the genesis of these disturbances is played by the relative increase in the activity of alpha 1-adrenoreceptors and decrease in beta-adrenoreceptor activity. Prazosin and nonachlazine in monotherapy reduced the number of anginal attacks and episodes of painless myocardial ischaemia.

[Use of beta 1-adrenostimulants in circulatory failure in patients with chronic inflammatory lung diseases]. / Primenenie beta 1-adrenostimuliatorov pri nedostatochnosti krovoobrashcheniia u bol'nykh s khronicheskimi vospalitel'nymi zabolevaniiami legkikh.

In 34 patients with chronic cor pulmonale, the drugs from a group of beta-adrenostimulants, nonachlazinum and oxyphedrinum, were tested for effects on their hemodynamics, pulmonary ventilation function, blood gas composition and acid-base balance. In patients with circulatory failure due to lung diseases, nonachlazinum and oxyphedrinum were found to exert a pronounced positive intropic action, to contribute to an increase in cardiac output. The agents may be included into the multimodality therapy of patients with decompensated chronic cor pulmonale.

[Cardiohemodynamics and microcirculation in patients with ischemic heart disease undergoing beta-adrenergic receptor stimulation and blockade]. / Kardiogemodinamika i mikrotsirkuliatsiia u bol'nykh ishemicheskoi bolezn'iu serdtsa pri stimuliatsii i blokade beta-adrenergicheskikh retseptorov.

A study of 76 patients with ischemic heart disease is presented who revealed during coronography stenosis of one-three coronary arteries equalling 50-75% of the vessel lumen. Analysis of the effect of anaprilin and nonachlazin on the clinical course and hemodynamics revealed that in patients with initial coronary atherosclerosis of middle age beta-adrenodependent vasodilation of the coronary arteries decreased. In these patients anaprilin may increase the frequency of attacks of spontaneous stenocardia. On the contrary, nonachlazin reduces manifestations of stenocardia but it may be used only in patients with a high tolerance to physical load.

[Effect of nonachlazine on the adenylate cyclase system of the rabbit heart]. / Vliianie nonakhlazina na adenilattsiklaznuiu sistemy serdtsa krolikov.

The influence of nonachlazine on the adenylate cyclase system of the rabbit heart was investigated. The faint beta-blocking activity (displacement of up to 20% of [3H]-dihydroalprenolol and inhibition of isoproterenol-stimulated activity) as well as the ability to stimulate basal activity in micromolar concentrations has been observed. Such combination of properties may be important in the realization of some positive effects of nonachlazine pharmacological activity.

[Mechanisms of the hemodynamic effects of nonachlazine in ischemic heart disease patients]. / K voprosu o mekhanizmakh gemodinamicheskikh éffektov nonakhlazina u bol'nykh ishemicheskoi bolezn'iu serdtsa.

During course therapy with nonachlazine of patients with ischemic heart disease, stable angina pectoris a negative inotropic effect of the drug in persons with eukinetic and in particular hyperkinetic type of hemodynamics was revealed. Enhancement of beta-adrenoblocking effect of nonachlazine with an increase of its daily dose was found. Nonachlazine effect on hemodynamic parameters was shown to be mediated through adrenoreactive structures.

[Possibility of the pharmacologic treatment of post-ischemic myocardial damage]. / Vozmozhnost' farmakologicheskogo vozdeistviia na postishemicheskoe povrezhdenie miokarda.

The influence of ethacizin and nonachlazin on the size of myocardial necrosis, caused by 1.5-hour partial occlusion of the coronary artery was studied in conscious rabbits. The drugs were administered for 3 days, after the blood supply in the ischemic zones had been recovered. Ethacizin had a more pronounced effect, as compared to nonachlazin. The data obtained suggest that in the case of isochemic heart disease pharmacotherapy can be used not only for the prevention and arrest of anginal attacks, but also for the treatment of postischemic cardiac lesions.

[Action of nonachlazine on the creatine phosphokinase and acid phosphatase activity and on the lysosomal membrane stability of the ischemic myocardium in rats after preliminary reserpinization]. / Deistvie nonakhlazina na aktivnost' kreatinfosfokinazy, kisloi fosfatazy i stabil'nost' lizosomnykh membran ishemizirovannogo miokarda krys posle predvaritel'noi rezerpinizatsii.

Experiments on the ischemic myocardial tissue of the rat in vitro showed that despite the fact that reserpine-induced depletion of the tissue catecholamine storage failed to affect the stability of lysosomal membranes, a combination of reserpine pretreatment of the animals with subsequent administration of nonachlazine at the low dose yielded stabilization of lysosomal membranes to a greater extent than administration of nonachlazine alone. The effects of nonachlazine (0.25 mg/kg) on the activity of creatine phosphokinase and total activity of acid phosphatase with and without reserpine pretreatment were similar.

[Use of ion-exchange sorbents for determining drug preparations and their metabolites in biological fluids by high-performance liquid chromatography]. / Primenenie ionoobmennykh sorbentov pri opredelenii lekarstvennykh preparatov i ikh metabolitov v biologicheskikh zhidkostiakh metodom vysokoéffektivnoi zhidkostnoi khromatografii.

High performance liquid chromatography has acquired great importance recently for an analysis of the drugs in biological fluids of the body. Phase inversion sorbents are particularly widely used today. However, the use of ion-exchange sorbents is fairly promising for an analysis of the drugs capable of ionizing in an aqueous solution. The authors illustrate the use of the latter ones for determination in the blood, urine and saliva of man of a number of the cardiologic drugs (etmozine, nonachlazine, verapamil, prazosin, propranolol, nadolol). Ion-exchange sorbents make it possible to attain better results than inverse phase ones, since they retain the drugs selectively and do not retain the endogenous substances of lipid nature. As regards verapamil, prazosin and propranolol, the unchanged drug and polar metabolites could be determined jointly, with such a determination being not feasible with the use of phase inversion sorbents. Separation of the diastereoisomers of nadolol was achieved in the blood and urine of patients who received the drug.

[Effect of nonachlazine on the temperature sensitivity of the lysosomal membranes of the heart muscle in rats in vitro]. / Vliianie nonakhlazina na temperaturnuiu chuvstvitel'nosti lizosomal'nykh membran serdechnoi myshtsy krys in vitro.

It has been shown in vitro that nonachlazine stabilizes rat myocardial lysosomal membranes and activates total acid phosphatase in homogenates of rat myocardium. Preliminary addition of nonachlazine to homogenates in two different final concentrations produces unequal changes in total and free activity of acid phosphatase and cathepsin D during 2.5-hour incubation of homogenates at 37 degrees C.

[Various aspects of the effects of beta adrenergic receptor blockaders, stimulants and calcium antagonists on the cardiovascular system]. / Izuchenie nekotorykh aspektov vliianiia na serdechno-sosudistuiu sistemu blokatorov i stimuliatorov beta-adrenoretseptorov i antagonistov kal'tsiia.

Experiments with isolated animal hearts showed that intracoronarily injected propranolol (beta-adrenoblocker) and nonachlasine (beta-adrenostimulator) lead to coronary dilatation changing into coronary constriction. Unlike propranolol, nonachlasine reduced the venous bed capacity. The use of nonachlasine resulted in primary reduction and consequent increase of myocardial contractility, propranolol leading to negative inotropic effect. The character and degree of the drug effect in hemodynamics depend on the initial activity of the sympathoadrenal system. The therapeutic effectiveness of the drugs also depends on the initial hemodynamic state and on the sympathoadrenal system activity. A comparative study of Ca2+ antagonists demonstrated corinfar to have positive ino- and chronotropic effect. Isoptine was shown to produce negative ino- and chronotropic action, with hemodynamics remaining indifferent to sensite. Ca2+ antagonists examined in the study are characterized by a diverse therapeutic effect and considerably differ in their influence on the circulatory system.

[Mechanisms of the inotropic action of nonachlazine]. / O mekhanizmakh inotropnogo deistviia nonakhlazina.

It has been demonstrated clinically and experimentally that administration of nonachlazine enhances myocardial contractility because of the stimulation of beta-adrenostructures and that the initial status of the latter ones determines in many respects the drug action intensity.

[Effect of nonachlazine on the size of an experimental myocardial infarct]. / Vliianie nonakhlazina na razmery éksperimental'nogo infarkta miokarda.

The effect of intravenous injection of nonachlazine on the infarction size in rabbits was studied planimetrically 7 days after coronary artery occlusion. The first group rabbits received the drug 5 times every 30 minutes, beginning from the 30th minute after occlusion (the total dose 15 mg/kg). The second group rabbits were given nonachlazine 3 times a day (the total dose 12 mg/kg) during 6 days, beginning from the 2nd day after coronary artery occlusion. In both the animal groups, the drug induced respectively a 22.8 and 39.4% decrease in the necrosis size as compared to control. The effect of nonachlazine is presumably linked with stimulation of the collateral coronary circulation in the occluded zone and with the drug direct action on myocardial metabolism.

[Biochemical basis for the spasmolytic effect of isoquinoline and phenothiazine derivatives]. / Biokhimicheskaia osnova spazmoliticheskogo éffekta proizvodnykh izokhinolina i fenotiazina.

Experiments with isolated ring-like strips of pig heart veins and arteries and those with rat small intestinal strips made in the presence of hyperpotassium contracture have demonstrated that spasmolytic activity of papaverine, nospa, nonachlazine, and ethmozine is a consequence of the reduced respiratory intensity and phosphorylation in smooth muscle mitochondria. No changes in the anaerobic glycolysis rate have been found after drug administrations.