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.

[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.

[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 energy provision for cardiac contractile activity in experimental myocardial infarct]. / Vliianie nonakhlazina na énergetichekoe obespechenie sokratitel'noi deiatel'nosti serdtsa pri éksperimental'nom infarkte miokarda.

Experiments on 107 rabbits and 76 white rats with the use of electrophysiological, biochemical and electron microscopy research methods have shown that nonachlazine-induced improvement of heart contractility in microfocal myocardial infarction occurs as a result of the shortening of the systolic and lengthening of the diastolic phases of the heart cycle. Nonachlazine improves the processes of oxidative phosphorylation in heart mitochondria in myocardial infarction, which is accompanied by inhibition of the activity of succinate dehydrogenase and transition of oxidation from succinate to NAD-dependent substrates.

[Effect of antianginal agents with a beta-adrenostimulating component of their action on the ischemic myocardium]. / Vliianie antianginal'nykh sredstv s beta-adrenostimuliruiushchim komponentom deistviia na ishemizirovannyi miokard.

Experiments on dogs with acute coronary insufficiency were made to show that nonachlazine in doses of 3 and 5 mg/kg considerably reduces or even prevents the rise of S-T segment on the epicardial electrogram depending on the intensity of ischemia. Hydroxyfedrine in doses of 0.1 and 0.3 mg/kg deteriorates the electrogram. Nonachlazine prevents an increase in the content of lactate and in the lactate/pyruvate ratio in the blood outflowing from the focus of ischemia. On the contrary, hydroxyfedrine raises the characteristics in question. Nonachlazine improves blood supply of the ischemized myocardium, increases the retrograde coronary blood flow and redistributes blood in favour of the affected myocardial area. Hydroxyfedrine lowers the retrograde blood supply of the area of ischemia and redistributes blood in favour of the unaffected areas of the heart.

[Use of computers for detecting the dynamics of changes in the cardiac adaptation reserves of alcoholism patients treated with nonachlazine]. / Ispol'zovanie EVM dlia vyiavleniia dinamiki izmenenii adaptatsionnykh rezervov sredtsa u bol'nykh alkogolizmon pri lechenii nonakhlazinom.

To reveal latent cardiac pathology in alcoholic patients'--the adaptation mechanisms adjusting the heart to the exercise test were quantitatively evaluated. The computer-made histograms of the cardiac rhythm of 30 practically healthy humans and 24 alcoholic patients showed before, during and after the exercise test that the variation range of the R-R interval was drastically decreased in alcoholic patients as compared to normal, while their mode was shifted towards shorter cardiointervals and had an increased amplitude. When the alcoholic patients were exposed to the exercise tests the shifts of the cardiointerval parameters in them were sharply different from those observed in the healthy subjects and after the test was over, the initial cardiac rhythm parameters failed to reappear within more than 3 min. Nonachlazin treatment of alcoholic cardiomyopathy increased the exercise tolerance estimated on the basis of the computer-processed cardiac rhythm, contributing to the reappearance of the normal clinical picture in the patients.

[Mechanism of the effect of anti-angina drugs with adrenergic beta receptor agonist action on the collateral hemodynamics and redistribution of the blood flow in chronic myocardial ischemia]. / K mekhanizmu vliianiia antianginal'nykh sredstv s beta-adrenostimuliruiushchim komponentom deistviia na kollateral'nuiu gemodinamiku i pereraspredelenie krovotoka pri khronicheskoi ishemii miokarda.

The experiments on dogs showed that in chronic myocardial ischaemia nonachlasine raising the retrograde arterial pressure and increasing the retrograde blood inflow to the ischaemic focus exerts a positive influence on the collateral cardiac haemodynamics. Raising the tonus of the coronary vessels in the intact regions of the myocardium to a greater extent than in the ischaemic region, nonachlasine redistributes the bloodflow to the advantage of the ischaemic zone. Oxyphedrin, decreasing of the ischaemic zone. Oxyphedrin, decreasing the tonus of the coronaries, especially in the intact areas of the myocardium, elicits the syndrome of "stealing" the zone of ischaemia.

[Mechanisms of action of nonachlazine]. / O nekotorykh mekhanizmakh deistviia nonakhlazina.

In animals with a ligated anterior descending left coronary artery, a single administration of nonaclazine (5 mg/kg bw) leads to a marked increase in the coronary blood flow and to an improvement in cardiovascular system function. Administration of nonachlazin for 7 days helps normalize the electrophysiological and hemodynamic characteristics and produces a beneficial effect on the myocardial blood flow and contractility. Interaction of nonaclazine with adrenergic receptors does not appear to have any decisive significance in the drug action mode.

[Effect of nonachlazine on brain and myocardial noradrenaline content in normal rats and rats subjected to stress]. / Vliianie nonakhlazina na soderzhanie noradrenalina v mozge i miokarde krys v norme i v usloviiakh stressa.

Nonachlazin causes a rapid and significant increase in the noradrenaline content of the rat myocardium and brain stem. The noradrenaline level falls in these tissues under stress reaction induced by immobilization and electric pain stimulation. Nonachlazin pretreatment before stress reaction prevents the decrease of the myocardial noradrenaline level and the development of cardiac ischemic disturbances and arrhythmias (according to the ECG data). However, nonachlazin fails to diminish the noradrenaline level in the brain stem under these conditions.

[Mechanism of action of nonachlazine and ethmozine on the cardiac blood supply in acute myocardial ischemia]. / K mekhanizmu deistviia nonakhlazina i étmozina na krovosnabzhenie serdtsa pri ostroi ishemii miokarda.

In anesthetized cats, intravenous administration of nonachlazin (1 and 6 mg/kg) and ethmozine (2 and 5 mg/kg) led, 5 minutes after ligation of the anterior descending branch of the left coronary artery, to the increased blood outflow from the coronary sinus and to a less marked elevation of myocardial oxygen consumption. The coronarodilatory effect of the drugs fell in the presence of a preliminary injection of the sympatholytic octadin (25 mg/kg intraperitoneally), atropine (0.5 mg/kg intravenously), alpha-adrenoblocker dihydroergotoxin (2 mg/kg intravenously), and beta-adrenoblocker obsidan (0.5 mg/kg intravenously). Nonachlazin and ethmozine decreased the pituitrin-induced (2 ED/kg intravenously) spasm of the coronary vessels of the affected heart.