[Formation of a new type of dinitrosyl iron complexes bound to cysteine modified with methylglyoxal].

It has been shown that interaction of cysteine dinitrosyl iron complexes with methylglyoxal leads to the formation of a new type of dinitrosyl iron complexes., EPR spectrum of these complexes essentially differs from spectra of dinitrosyl iron complexes containing unmodified thiol. The products of the cysteine reaction with methylglyoxal are hemithioacetals, Schiff bases and thiazolidines, which most likely serve as ligands for the new type of dinitrosyl iron complexes. It has been shown that the new type of dinitrosyl iron complexes as cysteine dinitrosyl iron complexes, which are physiological donors of nitric oxide, exert a vasodilator effect. It has also been found that the oxidative destruction of the new type of dinitrosyl iron complexes occurs at normal oxygen partial pressure, but these dinitrosyl iron complexes remain rather stable under hypoxia modeling. An assumption that the destruction of the new type of dinitrosyl iron complexes is caused by the formation of a bound peroxynitrite-containing intermediate is made.

Biopharmacology of enzyme conjugates: vasoprotective activity of supramolecular superoxide dismutase-chondroitin sulfate-catalase derivative.

Bienzyme conjugate was obtained by the covalent connection of superoxide dismutase with catalase through endothelial glycocalyx glycosaminoglycan - chondroitin sulfate (SOD-CHS-CAT). This SOD-CHS-CAT conjugate has vasoprotective activity in respect to platelet interactions, tonus of the ring arterial fragment of a rat blood vessel, as well as normalization of hemodynamic parameters in rats and rabbits in conditions of oxidative stress caused by the administration of hydrogen peroxide. The SOD-CHS-CAT conjugate had antiplatelet potential due to its antiaggregation action manifested through the combination of enzyme activities and an acquired supramolecular structure. The influence on arterial fragment tonus was equivalent for SOD and CAT in native and conjugated form. Blood pressure and heart rate were significant and effectively normalized with SOD-CHS-CAT conjugate in rats and rabbits (after hydrogen peroxide administration as a perturbance stimulus). We have discovered the possibility of using the antioxidant bienzyme conjugate in chronic prophylaxis. It is important for a real development of the oral form of the SOD-CHS-CAT conjugate. These results indicate that the development of enzyme conjugates can be medically significant, as a promising approach for the creation of new drugs.

[Prevention of reperfusion-induced arrhythmia by Na+/H+ exchange block]. / Preduprezhdenie reperfuzionnykh aritmii putem blokady Na+/H+ obmena.

Using the isolated papillary muscle and rat hearts, perfused by Langendorf, the effects of the Na+/H+ exchange blocker, ethylisopropylamiloride (EIPA), on electrical activity and contractility, and induction of ischemic and reperfusion arrhythmias were studied. In the experiments with regional ischemia and reperfusion of an isolated heart (the ligation of the left anterior descending coronary artery for 10 minutes), EIPA (5 microM) effectively abolished reperfusion fibrillations, reducing the incidence of the long fibrillations from 60% (in the controls) to 8%, and increased nearly five-fold the time interval prior to their onset. Antiarrhythmic action of EIPA seems to be unconnected with the direct block of ionic channels, because 5 microM of this compound did not significantly change the action potential parameters, first derivative Vmax and the contractile response of the papillary muscle in normal conditions. The results obtained show a significant role of the postischemic activation of the Na+/H+ exchange in the initiation of reperfusion-induced arrhythmias and possible use of amiloride derivatives for their prevention.

[Anti-arrhythmic and vasodilator actions of the antioxidant fenozan in acute ischemia and reperfusion]. / Antiaritmicheskoe i vazodilatornoe deistvie antioksidanta fenozana pri ostroi ishemii i referfuzii.

At the experiments with the isolated rat hearts, prepared by Langendorff, the anti-arrhythmic dose-effects of the water-soluble antioxidant fenozan from the class of steric-hindrance phenols were studied at condition of regional ischemia and reperfusion, as well as its action on the coronary flow. 3.6.10(-4) M of fenozan completely inhibited ischemic tachycardias, and diminished their incidence during reperfusion to 27%. The action of the fenozan in the concentration one order less, diminished total amount of reperfusion fibrillation to 67% (compared to 100% in control), the incidence of the long fibrillation to 67%, and considerably shifted their beginning to the moment of reperfusion. Dose-effects of anti-arrhythmic action of the antioxidant was V-shaped. Introduction of fenozan before 10 minutes of the occlusion caused an 1.5-2 hold increase of the coronary flow. This data show an effective antiarrhythmic and vasodilator action of the water-soluble phenol antioxidants during acute ischemia and reperfusion of myocardium.

[Anti-arrhythmia action of the antioxidant SD-6 in the development of ischemic and reperfusion rhythm disorders of the isolated rat heart]. / Antiaritmicheskoe deistvie antioksidanta SD-6 pri razvitii ishemicheskikh i reperfuzionnykh narushenii ritma izolirovannogo serdtsa krysy.

An antiarrhythmic action of water-soluble antioxidant SD-6 from 3-hydroxypyridine class and its effect on the transmembrane potentials were studied using the isolated rat heart and papillary muscle. Ischemia was induced by the occlusion of the left anterior descending coronary artery. 10 minutes later the ligation was removed and reperfusion was achieved. In the control, ischemia induced premature ventricular complexes, tachycardia and, in some cases, fibrillation. During perfusion total fibrillation occurred in 100% of the experiments. SD-6 in the doses of 10(-6) g/ml and 5 X 10(-6) g/ml significantly reduced the incidence of fibrillation and tachycardia. In the experiments on the papillary muscle SD-6 during reperfusion completely normalized the action potential duration and removed depolarization developed in hypoxia, which suggests the ability of the antioxidant to block reperfusion-induced arrhythmias by normalization of the parameters of electrical heterogeneity. These data show that the origin of reperfusion-induced arrhythmias is connected with the activation of free radical metabolites and that their scavengers--synthetic antioxidants from 3-hydroxypyridine class--can be used as new antiarrhythmic agents.

[Protective action of an antioxidant of the 3-hydroxypyridine class on the contractility and electrogenesis of the heart muscle in hypoxia and reoxygenation]. / Zashchitnoe deistvie antioksidantov iz klassa 3-oksipiridinov na sokratimost' i élektrogenez serdechnoi myshtsy pri gipoksii i reoksigenatsii.

The effect of SD-6, a 3-hydroxypyridine antioxidant, on the pattern of variation in contraction intensity, contracture and membrane potentials were assessed in experimental studies on isolated left ventricular papillary muscles of rats, exposed to hypoxia and reoxygenation. The antioxidant considerably limited hypoxic and reperfusion contracture, its efficiency increasing with a concentration reduced to 10(-7) g/ml. Contraction intensity and duration of action potentials, diminished by hypoxia, were only recovered by reoxygenation, if the antioxidant was present. It is assumed that the recovery of action potentials by reoxygenation in the presence of SD-6 may result from normalization of ATP-dependent outgoing current through the kappa channels, activated by ATP deficiency. The antioxidant capacity for levelling diverse durations of action potentials between normal and ischemic areas is evidence of an important contribution of free-radical mechanisms to the development of reoxidation-induced recirculation arrhythmias.

[Comparative analysis of the changes in myocardial electrical and contractile activity in rats exposed to rubomycin and its nitroxyl derivative]. / Sravnitel'nyi analiz izmenenii élektricheskoi i sokratitel'noi aktivnosti miokarda krysy pri deistvii rubomitsina i ego nitroksil'nogo proizvodnogo.

A comparative analysis was performed of changes in the contractile and electrical activity of the rat myocardium in experiments on isolated papillary muscles, obtained 2-2.5 months after the discontinuation of chronic administration of rubomicin in 0.7 mg/kg and ruboxil in 3 mg/kg dose to the animals. It is shown that rubomicin decreases the maximal rate of growth of the anterior potential of action and in a greater degree than ruboxil inhibits the contractile activity of papillary muscles. The preparations had a contrary influence on the rhythmoinotropic relations in the rat myocardium. This difference might be connected with the ability of rumobimicin to block and of ruboxil to stimulate Na-Ca metabolism. The participation of these mechanisms in the process of development of cardiotoxicity of antracycline antibiotics is discussed.