[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.

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.

[GLUCOSE CONTENT FLUCTUATION IN BLOOD OF NEWBORN RATS DEPENDING ON SEASON AND PATTERN OF SPONTANEOUS MOTOR ACTIVITY].

Earlier we have shown that in newborn rats the glucose level in blood serum changes depending on the pattern of spontaneous periodic motor activity (SPMA). During rest periods, both under dominant decasecond rhythm and under dominant minute rhythm, the glucose level in blood serum is higher than during activity periods. We have also shown that the glucose level in the blood serum rises with age reaching the level of adult animals by day 10. In the present study carried out on 3-10-day-old rats under conditions of free behavior the blood glucose content was investigated in different periods of <> cycle during different seasons. It is found that in newborn rats of all ages studied (3-, 5-, 7-, and 10-day-old ones) the lowest glucose concentration in the blood is observed in the winter period. In spring its level increases and in summer reaches the maximum different significantly from the winter and spring levels in all age groups except day 5. In autumn the glucose level decreases and approaches the spring values but it is still different from the winter indices. In 5-day-old rats statistically significant differences of glucose levels in different seasons were not observed. The data obtained provide evidence of seasonal fluctuations of the glucose level in blood serum of newborn rats. At the same time during all seasons except spring the dependence of glucose level on the pattern of motor activity persists. In spring these differences are smoothed. Key words: ontogenesis, motor activity, metabolic factors, glucose, seasonal variations.

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.

[The blood glucose content in newborn rats depending on level and pattern of spontaneous motor activity].

Earlier we have shown that administration to newborn rats of the pentose phosphate cycle inhibitor hydroquinone leads to a change in intensity and pattern of spontaneous periodic motor activity (SPMA) characteristic of early stages of development. The most typical was the disappearance of the rest period from the near-minute cycle "activity--rest" and the appearance of uninterrupted motor activity. In several cases, especially after 10 days of development, there was noted an enhancement in the SMPA pattern of the motor activity complexes following in the decasecond rhythm. In this study, on the 3-10-day old rats maintained under conditions of free behavior there was studied the blood glucose content in the animals at various periods of the activity-rest cycle. Apart from the SPMA phase, its composition (pattern) characterizing the maturity level and functional state of spinal motor centers was taken into account. In the 3, 7 and 10-day old rats at the rest period, the glucose concentration was established to differ depending on the motor activity pattern. In the case of the decasecond periodicity, it amounts to 5.7 +/- 0.2, 6.3 +/- +/- 0.3, and 7.7 +/- 0.3 mmol/l, while at the minute one--6.1 +/- 0.4, 7.8 +/- 0.3, and 7.8 +/- 0.1 mmol/l. At the moment of bursts of motor excitation, the glucose concentration falls to 5.2 +/- 0.1, 6.1 +/- 0.4, and 7.1 +/- +/- 0.3 mm at the decasecond and to 5.4 +/- 0.5, 6.7 +/- 0.2, and 7.6 +/- 0.3 mmol/l at the near-minute rhythm (for the 3, 7 and 10-day old animals, respectively). The results obtained on the 5-day rat pups differ qualitatively from those observed in other age groups. Thus, the glucose concentration at the rest period amounts to 6.8 +/- 0.2 at the decasecond and to 6.7 +/- 0.4 mmol/l at the nearminute periodicity. At the period of motor excitation accompanied by the presence of the decasecond activity rhythm, the glucose concentration falls to the level of 6.0 +/- 0.2 mmol/l by differing statistically significantly from the observed one in the rest state. In the case of the appearance of the minute rhythm, the glucose concentration amounts to 5.8 +/- +/- 0.3 mmol/l. The obtained data indicate that reproduction of the minute and decasecond rhythms recorded in composition of SPMA is accompanied by a change in the blood serum glucose level. The degree of a decrease of its concentration correlates with a certain activity rhythm: at the decasecond one the fall is 9, 13, 3, and 7 %, whereas at the minute rhythm--11, 13, 14, and 2% (for the 3-, 5-, 7- and 10-day old rats, respectively). In id to be noted that a certain effect on the activity pattern is produced by the degree of satiety of the rat pups, the gastric emptying being accompanied by an increase in expression of the decasecond rhythm and of brief jerks. Besides, there occur the significant seasonal oscillations of the blood serum glucose concentration in the newborn rat pups--at the summer period it is statistically significantly higher than at the winter-spring period.

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.

Neuroprotective effect of cytoflavin during compression injury of the spinal cord.

Cytoflavin normalized energy metabolism, decreased the intensity of lipid peroxidation, and reactivated the antioxidant system in the spinal cord of rats with compression injury at the level of Th10-Th11. The neuroprotective effect of the test preparation manifested in normalization of hindlimb motor function and decrease in mortality rate of animals with spinal cord injury. Neuroprotective activity of cytoflavin was higher than that of Cerebrolysin.

[The neuroprotector effect of a new taurine derivative on a model of compression spinal cord trauma in rats].

The neuroprotector effect of a new taurine derivative, 2-(1-phenylethyl)-aminoethanesulfonyl-2-propylamide hydrochloride, has been studied in rats with model compression spinal cord trauma. The drug favored restoration of the motor function of posterior extremities in rats with the model spinal cord trauma and significantly decreased the lethality in test animals. The taurine derivative normalized the energy metabolism, lipid peroxidation and antioxidant system in animals with spinal cord trauma. The neuroprotector effect of the new taurine derivative significantly exceeds the action of cerebrolysine.