Clinical and experimental study of antiarrhythmic and antianginal effects of quaternidine

High antiarrhythmic activity of a new Russian antiarrhythmic drug quaternidine in ventricular arrhythmia was studied in 96 coronary patients by Holter monitoring, bicycle ergometry, and echocardiography. The drug had a positive impact on local kinetics in left-ventricular ischemic myocardium and some parameters of bicycle exercise test. The preparation possesses no arrhythmogenic effect. Experiments on 30 random-bred rats showed that the drug reduced the necrotic zone under conditions of experimental coronary occlusion. Experiments on 14 intact cats demonstrated that quaternidine had no effect on coronary bloodflow.     

Effect of biotechnological cytochromec on the early postocclusion and reperfusion arrhythmias

Biotechnological cytochromec showed a lower antiarrhythmic activity in cats with acute occlusion and reperfusion arrhythmias than trimecaine, verapamil, and quaternidine but a higher activity than anapriline. Under experimental conditions, cytochromec potentiated the antiarrhythmic effect of trimecaine and quaternidine. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 127, No. 1, pp. 89–91, January, 1999     

Involvement of central and peripheral cannabionoid receptors in the regulation of heart resistance to arrhythmogenic effects of epinephrine

Intravenous injection of the selective cannabinoid receptor agonist HU-210 in doses of 0.05 and 0.25 mg/kg increased heart resistance to arrhythmogenic effects of epinephrine, while intracerebroventricular infusion of this substance had no effect on the incidence of epinephrine-induced arrhythmia. The selective antagonist of type I cannabinoid receptors SR141716A in a dose of 3 mg/kg and ganglion blocker hexamethonium in a dose of 10 mg/kg did not modify the antiarrhythmic effect of HU-210. This effect of HU-210 is probably related to activation of type II peripheral cannabinoid receptors. Translated fromByulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 130, No. 11, pp. 552–554, November, 2000     

Do endogenous ligands of peripheral μ- and δ-opiate receptors mediate antiarrhythmic and cardioprotective effects ofRhodiola rosea?

Oral administration ofRhodiola rosea extract to rats (3.5 ml/kg, 8 days) prevents reperfusion arrhythmias and elicits a protective effect in experiments on isolated heart. Experiments with naloxone and ICI 174,864 suggest that the antiarrhythmic effect ofR. rosea extract is mediated through activation of μ-opiate receptors in the myocardium. The cardioprotective effect of this extract is not associated with opiate receptors. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 124, No. 8, pp. 151–153, August, 1997     

Antiarrhythmic activity of GABA derivative TZ-50-2

The GABA derivative TZ-50-2 exerted pronounced antiarrhythmic effects on a variety of arrhythmias (atrial, ventricular, and mixed). The drug was superior (or at least comparable) to quinidine, procainamide, lidocaine, verapamil, bonnecor, and other reference drugs in antiarrhythmic activity and therapeutic range, and showed no cardiotoxicity. The antiarrhythmic effects of TZ-50-2 were due to modulation of calcium and sodium channels. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 127, No. 4, pp. 415–418, April, 1999     

Membrane Mechanisms of Antiarrhythmic Effect of Quaternidine

Complex electrophysiological study of the effects of quaternidine carried out on intact hearts from cats, myocardial fragments from rats, and single ionic channels of large edible snail showed that quaternidine demonstrates properties of class 1B antiarrhythmic drug according to Vaughan-Williams nomenclature. This agent did not suppress nomotopic pacemaker automaticity, did not change conduction in ventricles, atria, and atrioventricular junction in hearts with preserved sinus rhythm, did not prolong refractoriness of the atria and atrioventricular junction, but prolonged efficient refractory period of heart ventricles. Quaternidine decelerated rapid depolarization of the action potential, but had no effect on its duration. It did not affect potassium conductance.__________Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 139, No. 6, pp. 656–659, June, 2005     

Implication of sympathetic innervation of the heart in antiarrhythmic action of intra-atrial laser irradiation

The role of sympathetic nervous system in the antiarrhythmic effect of intra-atrial laser irradiation (λ=632.8 nm) during myocardial ischemia was studied in acute experiments on Nembutal-anesthetized cats. Laser irradiation applied after bilateral, dextral, or sinistral transection of cardiac branches of stellate ganglia increased the number of ischemic rhythm disturbances that developed after occlusion of the circumflex branch of the left coronary artery. The maximum increase in the number of arrhythmias was observed after dextral transection, the occurrence of ventricular fibrillation being 100%. Bilateral transection provoked a larger number of ischemic rhythm disturbances than the sinistral transection. It is probable that the development of the antiarrhythmic effect of laser irradiation requires sustained sympathetic activity targeted at the nonischemic regions in the myocardium that could play a stabilizing role during local ischemic damage to the heart. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 126, No. 11, pp. 522–526, November, 1998     

Antiarrhythmic effect of hypoxic preconditioning is mediated by activation of μ- and δ-opioid receptors

Adaptation of rats to repetitive hypoxia leads to a decrease in the severity and frequency of arrhythmias induced by epinephrine. Naloxone abolishes antiarrhythmic effect of adaptation. Activation of μ-and δ-opioid receptors is one of the important factors mediating antiarrhythmic effect of adaptation. Intravenous administration of acetorphan, an enkefalinase inhibitor, produces statistically significant antiarrhythmic effect in the control group. Thus, the antiarrhythmic effect of hypoxic adaptation results from activation of μ-and δ-opioid receptors due to increased level of endogenous enkefalins. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 125, No. 3, pp. 272–274, March, 1997     

Role of ATP-sensitive K<Superscript>+</Superscript>-channels in antiarrhythmic and cardioprotective action of adaptation to intermittent hypobaric hypoxia

Mature Wistar rats were exposed to intermittent hypobaric hypoxia (5000 m, 6 h/day, 30 sessions). This mode of adaptation enhanced heart tolerance to the arrhythmogenic action of 45-min coronary occlusion, but does not affect the infarction size/risk area ratio. In some series, the rats were exposed to more severe intermittent hypobaric hypoxia (7000 m, 8 h/day, 6 weeks) followed by 20-min coronary occlusion and 3-h reperfusion one day after the last hypoxia session. In this case, adaptation reduced the infarction size/risk area ratio and enhanced cardiac tolerance to the arrhythmogenic effect of reperfusion, but had no effect on the incidence of ventricular arrhythmia during ischemia. We found that the cardioprotective and antiarrhythmic effects of adaptation to an altitude of 7000 m and the antiarrhythmic effect of 5000-m adaptation were mediated via activation of K_ATP channels. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 145, No. 4, pp. 395–398, April, 2008     

Prevention of experimental epinephrine-induced arrhythmias with agonists of δ1- and δ2-opiate receptors

Agonists of δ₁- and δ₂-opiate receptors prevent epinephrine-induced arrhythmias in rats after intracerebroventricular administration. The antagonist of δ-opiate receptors ICI 174,864 blocks antiarrhythmic effect of the selective agonist of δ-opiate receptors DTLET and exhibits no antiarrhythmic activity by itself. It is shown that antiarrhythmic effect of DTLET is associated with increased vagal tone. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 124, No. 9, pp. 286–288, September, 1997     

Protective effect of neurotensin during vagal arrhythmias

The effects of neurotensin and its analog [d-Trp¹¹]-neurotensin were studied on Wenckebach arrhythmia and atrioventricular dissociation provoked by vagal volley stimulation. In both cases the antiarrhythmic effect of neurotensin was observed, which was mediated by activation of cardiac β-adrenoreceptors and manifested 40–60 sec after its administration. The neurotensin analog had no cardioprotective activity, but when applied before neurotensin, it demonstrated antagonism to the protective effect of natural neurotensin. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 124, No. 11, pp. 495–497, November, 1997     

Opiatergic mechanisms of cardioprotective and antiarrhythmic effects of adaptation

Adaptation to hypoxia and short-term immobilization stress, as well as preconditioning with Rhodiolae rosea extract produces pronounced antiarrhythmic and cardioprotective effects in the model of adrenergic damage to the heart. Preliminary blockade of opioid receptor significantly decreases the protective effect of adaptation. Using selective opiate receptor antagonists (naltrindole, ICI 174,864, and norbinaltorphimine) we show that the antiarrhythmic effect of adaptation is mediated predominantly via activation ofk-receptors, and to a lesser extent μ-and σ-receptors. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 127, No. 2, pp. 167–170, February, 1999     

Comparative study of Na-blocking properties of antiarrhythmic drugs on isolated rat cardiomyocytes

The effects of the antiarrhythmic preparations lidocaine, flecainide, and rhlocaine on sodium concentration in cardiomyocyte cytoplasm are studied using the Na-sensitive fluorescent probe SBFI. The Na-blocking effect of lidocaine and rihlocaine depends on the frequency of electrical stimulation of cardiomyocytes (0.2–1.0 Hz). The data suggest the possibility ofin vitro testing of novel antiarrhythmic drugs. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 123, No. 6 pp. 666–668, June, 1997     

Effect of suphan, lidocaine, and their combination on early occlusion and reperfusion arrhythmias in cats

It is shown that the nonglycoside cardiotonic drug suphan exhibits antiarrhythmic and antifibrillatory activity, although less pronounced than that of lidocaine. When lidocaine was administered after suphan, the antifibrillatory effects of both preparations increased. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 123, No. 5, pp. 545–547, May, 1997     

Comparative characteristics of antiarrhythmic activity of phencarol and dimebone in neurogenic ventricular fibrillation

The antihistamine drugs (H₁-blockers) dimebone and especially phencarol exhibit antiarrhythmic activity under conditions of neurogenic ventricular fibrillation. The antiarrhythmic activity of phencarol is associated with pronounced vagolytic effect, while that of dimebone is due to both vagolytic and moderate cardiotropic effect. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 124, No. 7, pp. 81–85, July, 1997     

Role of vagus nerves in antiarrhythmic effect of DAGO in acute myocardial ischemia

Acute experiments on cats show that DAGO, a selective μ-opiate receptor agonist, elicits a pronounced antiarrhythmic effect in ischemia-induced arrhythmias. The protective effect of DAGO is observed only under conditions of intact parasympathetic innervation of the heart and apparently depends on then. vagus activity and stimulating effect of DAGO on acetylcholine release. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 124, No. 10, pp. 377–379, October, 1997     

Antiarrhythmic activity of the antiopioid peptide nociceptin and its effect on the fast Na+ channels in cardiomyocytes

The antiopioid peptide nociceptin does not affect heart resistance to the proarrhythmic effect of epinephrine or calcium chloride, but it produces an antiarrhythmic effect in the aconitine arrhythmia model. Nociceptin prolongs the QRS interval and does not affect heart rate and duration of the RQ interval. The antiarrhythmic effect of nociceptin is not related to changes in the tone of the autonomic nervous system. Nociceptin is supposed to block fast Na⁺ channels in cardiomyocytes. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 126, No. 12, pp. 655–657, December, 1998     

Effect of befol and sufan on neurogenic atrial fibrillation

Antiarrhythmic activity of befol in neurogenic atrial fibrillation is due to its cardiotropic and cholinolytic effects and coincides with the dynamics of the tonic component of vagal chronotropic influence. Unlike befol, sufan has no effect on the duration of atrial fibrillation despite a reduction of synchronizing component of the vagal chronotropic influence. Tonic component remains unchanged, which is probably responsible for the absence of antiarrhythmic activity of sufan. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 125, No. 4, pp. 404–406, April, 1998     

Neurochemical characteristics of the effects of delta sleep-inducing peptide in wistar rats with hyperactivity of the dopaminergic system

Quantitative cytochemical assay showed that single injection of delta sleep-inducing peptide increased monoamine oxidase activity (substrates: serotonin and tryptamine) in the caudate and accumbens nuclei and glutamate dehydrogenase activity in the hippocampus of stress-resistant Wistar rats chronically treated with L-DOPA. Enzyme activities in the sensorimotor cortex did not change. Delta sleep-inducing peptide had no effects on acetylcholine esterase and aminopeptides activities in the brain of Wistar rats. Translated fromByulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 130,No. 11, pp. 537–539, November, 2000     

Cardiotoxic effects of the antiarrhythmic rhythmidazol and their correction by suphan, befol, and their combinations

The antiarrhythmic rhythmidazol produces a cardiotoxic effect that can be corrected by suphan, befol, and their combinations, as evidenced by normalization of ultrastructural organization of cardiomyocytes and myocardial oxygen consumption by these drugs. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 124, No. 12, pp. 640–644, December, 1997