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 galantamine and testosterone on the arthritic response and dopamine content in rat spleen].

The study was carried out on male Wistar rats with surgically ablated gonads. The rats with gonadectomy and intact rats received galantamine and/or testosterone over 10 days, after which the model arthritis was induced by injection of 200 ml of complete Freund's adjuvant. It was established that gonadectomy reduced arthritic reactions producing ulcer formation at a later time (21 days) as compared to control (rats with arthritis), where they are formed on the local stage of development (day 7). Testosterone replacement therapy completely blocks the development of ulcers on the paws. Galantamine suppresses the arthritic reaction more significantly, reducing paws and ankle-joint edema 1.5 and 1.3 times respectively (n = 12, p <0.05). The appearance of dopamine in the spleen during galantamine treatment may serve as a marker of protective action of the drug under hypoandrogenic conditions. Introduction of galantamine at high level of testosterone does not significantly influence on development of arthritic reaction, which is indicative of a marked imbalance between the hormonal and cholinergic systems and a possibility to modulate arthritic reaction with cholinergic drugs.

[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.

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.

Effects of cytoflavin and neuronol on morphological changes in the brain and survival of rats with ischemic disturbances in cerebral blood flow.

Cytoflavin and neuronol produce vasoactive and neuroprotective effects in rats with cerebral ischemia. Vasoactive activity of neuronol was higher than that of cytoflavin. These differences were most pronounced at the level of microcirculation. Test preparations were equally potent in producing the neuroprotective effect. Cytoflavin and neuronol markedly decreased the mortality rate of animals. Over the first 6 h of ischemia the relative effectiveness of cytoflavin was higher than that of neuronol. However, neuronol exceeded cytoflavin in the relative effectiveness during the follow-up period (days 1-21).

[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.

[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.

[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 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.

[Anti-arrhythmic action of adenosine and the cyclic nucleotide content of the myocardium of rats with ischemia]. / Antiaritmicheskoe deistvie adenozina i soderzhanie tsiklicheskikh nukleotidov v miokarde krys pri ishemii.

In anesthetized rats a 30-min intravenous infusion of adenosine (2.5 mg/kg/min) performed after the coronary artery ligation significantly decreased the incidence and severity of early ischemic arrhythmias. After the infusion of adenosine, there was an increase in cGMP level in the left ventricular myocardium, cAMP content remained unchanged.

[Effect of guanosine-5'-monophosphate and inosine on the isolated heart of the frog]. / Deistvie guanozin-5'-monofosfata i inozina na izolirovannoe serdtse liagushki.

The chronotropic and inotropic effects of guanosine-5'-monophosphate (5'-GMP) and inosine were investigated in isolated frog hearts. 5'-GMP induced biphasic chronotropic and inotropic responses: positive those were inhibited with propranolol, the negative inotropic response could not be inhibited with atropine. Inosine was able to enhance the positive inotropic response to 5'-GMP.