Antiarrhythmic Activity of Taurepar during Ischemic and Reperfusion Damage to Myocardium.

The antiarrhythmic effect of taurepar, an N-phenylalkyl derivative of taurine, was examined in experiments on rats subjected to acute myocardial ischemia/reperfusion leading to arrhythmia development. During acute ischemia, taurepar (25 mg/kg) completely prevented early postocclusion arrhythmias including extrasystoles, ventricular tachycardia, and ventricular fibrillation. During postischemic reperfusion, taurepar (25 mg/kg) did not prevent extrasystoles and ventricular tachycardia, but precluded the development of ventricular fibrillation and the death of animals. The antiarrhythmic potency of taurepar surpassed that of lidocaine during acute myocardial ischemia and that of propranolol during ischemia/reperfusion injury. The results suggest that taurepar is a promising antiarrhythmic drug with high antifibrillation activity.

Antiarrhythmic effect of uridine and uridine-5'-monophosphate in acute myocardial ischemia.

Experiments on rats with acute myocardial ischemia accompanied by early postocclusive arrhythmias have shown normalizing, energy-stabilizing, and antiarrhythmic effects of uridine and uridine-5'-monophosphate. The drugs decreased lactate and restored reserves of glycogen and creatine phosphate depleted by ischemia. Uridine and uridine-5'-monophosphate significantly decreased the severity of ventricular arrhythmias. Both drugs reduced the incidence and duration of fibrillation. Uridine -5'-monophosphate demonstrated most pronounced antifibrillatory effectiveness. We hypothesize that the antiarrhythmic effect of the drugs is determined by their capacity to activate energy metabolism.

Effect of uridine on energy metabolism, LPO, and antioxidant system in the myocardium under conditions of acute coronary insufficiency.

Experiments on rats have shown that preventive treatment with uridine stabilizes energy metabolism in the heart under conditions of 60-min left coronary artery occlusion. The preparation also prevented antioxidant system dysfunction and LPO hyperactivation. 5-Hydroxydecanoate, a selective blocker of mitochondrial ATP-dependent K(+)-channels, abolished the protective effect of uridine, which attested to the involvement of these channels into mechanisms of the cardioprotective effect of the preparation. The elimination of intravenously administered uridine from the blood of animals with acute ischemia was accelerated in comparison with that in intact animals, which could suggest the participation of this nucleoside in the processes of activation of intracellular anti-ischemic defense mechanisms.

[Protective effect of uridine on metabolic processes in rat myocardum during its ischemia/reperfusion damage]. / Zashchitnoe deistvie uridina na metabolicheskie protsessy v miokarde krys pri ego reperfuzionnom povrezhdenii.

The experimental study of the cardioprotective effect of uridine, the metabolic precursor of the endogenous activator of mitochondrial ATP-dependent K+-channels (mitoKATP-channels), was performed using the model of myocardial ischemia/reperfusion (I/RP) in rats. Ischemia for 30 min followed by reperfusion for 120 min resulted in a significant decrease in ATP and phosphocreatine (PC) content, intensification of lipid peroxidation (LPO), and inhibition of the antioxidant system (AOS) in cardiomyocytes. Uridine in a dose of 30 mg/kg, administered intravenously prior to reperfusion, had a protective effect on myocardial metabolism in the I/RP zone. It prevented the decrease of ATP and PC, limited the LPO processes, evaluated by the content of lipid hydroperoxides and conjugated dienes, and improved the AOS state by, preventing the decrease of superoxide dismutase (SOD) activity and increasing the content of reduced glutathione (GSH). The mitoKATP-channel blocker 5-hydroxydecanoate (5-HD, 5 mg/kg) eliminated the ability of uridine to maintain the ATP level and to exhibit its positive effect on the intensity of the LPO and activity of AOS. The obtained data allow us to conclude that activation of mitoKATP-channels play an important role in the mechanism of the cardioprotective effect of uridine in I/RP damage of myocardium.

[Mitochondrial ATP-dependent potassium channel. 2. The role of the channel in protection of the heart against ischemia].

The cardioprotective properties of pharmacological and metabolic activators of mitoKATP are reviewed. Metabolic activators of the channels and data on their cardioprotective properties are discussed in the review. The authors adduce their own data concerning cardioprotective properties of mitoKATP channel metabolic activator (UDP). In experimental animals, UDP precursors, uridine and UMP, decrease myocardial ischemic alteration index and T-wave amplitude within 60 min after occlusion of the left coronary artery. Both effects are prevented by mitoKATP channel inhibitors, glibenclamide and 5-HD. UMP and uridine possess antiarrhythmic properties as well. These preparations decrease the number of premature ventricular beats, the duration of ventricular tachycardia and fibrillation, and these effects are eliminated mainly by glibenclamide. Thus, mitoKATP plays a significant role in prevention of both ischemic lesions and rhythm disorders. The prospects of application of metabolic activators to prevent and treat myocardial infarction are discussed.

[Effect of adenosine on the size of experimental myocardial infarction and "no re-flow" areas]. / Vliianie adenozina na razmer eksperimental'nogo infarkta miokarda i velichinu zony "nevosstanovleniia krovotoka".

In rabbit experiments, adenosine was studied for its effects on the sizes of myocardial infarction and "no reflow" zones after coronary artery occlusion and reperfusion. Intravenous administration of adenosine resulted in a steady drop in blood pressure, decrease in heart rate and increase in the extent of infarction and "no reflow" zone.

[Hemodynamic and metabolic effects of adenosine in experimental myocardial infarction]. / Gemodinamicheskie i metabolicheskie éffekty adenozina pri eksperimental'nom infarkte miokarda.

Adenosine, administered intravenously (0.25 mg/kg-1/min-1) to rabbits with experimental myocardial infarction, produced a drop in arterial pressure and total peripheral resistance, normalized stroke volume, increased ATP content at the margin of the infarcted area, and reduced LDG activity and increased SDG activity in the ischemized region.

[Changes in the microcirculation in the rat mesentery during hypotension induced by adenosine]. / Izmeneniia mikrotsirkuliatsii v bryzheike krysy pri gipotonii, vyzvannoi adenozinom.

In anesthetized rats, i.v. administration of adenosine (2.5 mg/kg/min) for 30 min caused reduction of mean systemic blood pressure. A significant decrease of blood flow was found in mesentery microvessels as well as dilation of arterioles and venules.

[Adenosine pharmacokinetics in rats]. / Farmakokinetika adenozina u krys.

The pharmacokinetics of the effective peripheral vasodilator adenosine in blood serum of rats was studied after its intravenous injection. The dynamics of labeled adenosine in blood was described by means of a one-compartment mathematical model. The pharmacokinetic parameters of the drug were calculated from the model coefficients. The distribution of the label of adenosine and its metabolites in blood serum and heart, liver, and kidney tissues was studied by thin-layer chromatography.

[The role of the muscarinic, adenosine and adrenoreceptors of the heart in the development of postischemic reperfusion ventricular fibrillation]. / Rol' muskarinovykh, adenozinovykh i adrenoretseptorov serdtsa v razvitii postishemicheskoi reperfuzionnoi fibrilliatsii zheludochkov.

The authors studied the effect of m-cholino-, adreno-, and purinotropic agents on the development of postischemic reperfusion fibrillation of isolated rat hearts. Pilocarpine, norepinephrine, phenylephrine, and adenosine caused a proarrhythmogenic effect. Atropine, trimedoxim, prazosin, and chloroquine made fibrillation less expressed. A direct correlation was found between the arrhythmogenic effect of reperfusion and the size of the no-reflow zone, with the use of the drugs too. It is concluded that the phospholipid mechanism contributes to realization of the arrhythmogenic effect of reperfusion and vascular disorders, leading to the occurrence of the no-reflow phenomenon.

[Effect of purine nucleosides on the contractile function of the rat heart in ischemia and reperfusion]. / Vliianie purinovykh nukleotidov na sokratitel'nuiu funktsiiu serdtsa krys pri ishemii i reperfuzii.

The Langendorf isolated rat hearts underwent 30-minute total ischemia followed by 60-minute reperfusion. Adenosine, inosine or guanosine was added at a concentration of 50 mumol/l into the perfusate in the first 30 minutes. The nucleotides significantly increased the developed pressure and the maximum left ventricular contractility rate. The most effective agent was adenosine which also made blood flow higher. Guanosine was more effective than adenosine and inosine in protecting the heart from ischemic contracture. At the same time adenosine augmented the arrhythmogenic effect of reperfusion, by significantly elevating the cardiac levels of diene conjugates and malonic dialdehyde. It is suggested that the arrhythmogenic effect of adenosine is the result of activated lipid peroxidation due to adenosine exchange via the xanthine reaction during nucleotide-induced vasodilation.

[Action of regulators of peripheral cholinergic processes on development of early arrhythmia in myocardial ischemic rats]. / Vliianie reguliatorov perifericheskikh kholinergicheskikh protsessov na razvitie rannikh aritmii u krys pri ishemii miokarda.

Occlusion of the left coronary artery in rats provoked ventricular tachycardia (VT) and ventricular fibrillation (VF) within the first 30 min of ischemia leading to death in 20% animals. Methacin (i.v., 100 micrograms/kg) significantly prolonged VT and VF without effects on the survival. Acetylcholine (i.v., 10 micrograms/kg/min) had no influence on VT frequency and severity but prevented VF. Rats from this group survived. The same effect was observed for neostigmine (i.v., 25 micrograms/kg). Nicotine (i.v., 2.5 micrograms/kg/min) prolonged VT episode duration but did not change frequency and severity of VF and survival. Ganglioblockers hexametony and azametony (i.v., both in a dose 500 micrograms/kg) significantly attenuated VT, prevented VF and death of the animals. Thus, cholinotropic drugs may have both antiarrhythmic and proarrhythmogenic effects in early arrhythmias induced by ischemia.

[The effect of a new phenylalkyl taurine derivative on the size of the necrotic area in experimental myocardial infarct in rats]. / Vliianie novogo fenilalkil'nogo proizvodnogo taurina na razmer zony nekroza pri éksperimental'nom infarkte miokarda u krys.

The study of an anti-ischemic action of a new phenilalkyl taurin derivative TAU-60 has discovered that this drug attenuates ECG signs of myocardial infarction and reduces the size of necrosis zone on the anterior wall of the left ventricular myocardium in rats with experimental myocardial infarction.

Comparative study of cardioprotective effects of uridine-5'-monophosphate and uridine-5'-triphosphate during the early periods of acute myocardial ischemia.

In experiments on rats, uridine-5'-monophosphate and uridine-5'-triphosphate reduced the intensity of anaerobic glycolysis and preserved glycogen stores and creatine phosphate balance during the first 60 min after occlusion of the left coronary artery. However, the energy-protective effect of uridine-5'-triphosphate developed 15 min later than the effect of uridine-5'-monophosphate. Uridine-5'-monophosphate, but not uridine-5'-triphosphate, reduced T wave amplitude on ECG and decreased the volume of ischemic injury to the myocardium.

Cerebroprotective effect of a new taurine derivative during cerebral ischemia.

A new taurine derivative chlorohydrate-N-isopropylamide-2-(1-phenylethyl)aminoethanesulfonic acid normalized energy metabolism, inhibited lipid peroxidation, and reactivated antioxidant enzymes in the brain of rats exposed to ischemia. This taurine derivative decreased the mortality rate of animals with ischemic changes in cerebral circulation. The test compound was more potent than piracetam in producing the cerebroprotective effect.

Antiarrhythmic activity of taurhythman.

Antiarrhythmic properties of taurhythman were demonstrated on experimental models of ventricular (early occlusion and calcium chloride-induced) and atrioventricular (aconitine-induced) arrhythmias. The preparation reduced or prevented episodes of paroxysmal tachycardia and ventricular fibrillation, decreased the incidence of arrhythmias, and increased the lethal dose (LD) of arrhythmogenic agents. By its efficiency, taurhythman was superior to procainamide and comparable to lidocaine.

[Dependence of cardiovascular effects of adenosine on the blood circulation type in rats]. / Zavisimost' kardiovaskuliarnykh éffektov adenozina ot tipa krovoobrashcheniia u krys.

Administration of adenosine increased the RR interval in greater degree at hyper- than in hypodynamic blood circulation type. The AV-blockade and atrial flutter were maximal in rats with hyperdynamic type of blood circulation. Propranolol weakened the adenosine cardiotropic effect whereas cholinoblockators enhanced it. Neurohumoral regulation exerted no effect on the adenosine hypotensive action.

[Effect of adenosine on hemodynamic changes during the development of neurogenic myocardial lesions]. / Vliianie adenozina na izmeneniia gemodinamiki pri razvitii neirogennykh porazhenii miokarda.

The influence of adenosine on hemodynamic changes induced by electrostimulation of reflexogenic zone of aorta was studied in this article. It was shown that 3-hour electrostimulation increased the total peripheral resistance and decreased cardiac output and aortic pressure. Intravenous infusion of adenosine during electrostimulation led to the normalization of main indices of hemodynamics.