Prolonged perfusion of rat brain with a high oxygen tension solution, without oxygen carriers and with an external normal barometric pressure.

BACKGROUND: Isolated brain of experimental animals is a useful model to study transport of substances, including drugs, across the blood-brain barrier, mechanisms of convulsive activity, ischemic and reperfusion brain injury. Normal functioning of neurons, especially cortical, in the central nervous system requires adequate supply of oxygen. Therefore oxygen carriers or fluorocarbon substances with high oxygen capacity are often used in animal brain perfusion experiments. NEW METHOD: In the present study of the in situ rat brain perfusion oxygen carriers were not used. The optimum oxygen capacity of the perfusion media (adequate to the arterio-venous difference) was achieved by a high oxygen tension (2400-2600 mm Hg) in the solution under normal barometric pressure. Perfusate was depressurized and delivered at normal rat systemic hydrostatic pressure to the brain via a cannula inserted transcardially into the ascending aorta, with both subclavian arteries ligated. Perfusate was delivered using normal hydrostatic pressure. RESULTS: In these experimental conditions of the brain perfusion the pattern of electrocorticogram has been stable in the course of 5 h and more. The release of lactic acid in the perfusion solution was 3 times less than in perfusion under partial oxygen tension of 900 mm Hg; excessive activation of the lipid peroxidation process in the brain tissue was not observed. CONCLUSION: The presented new model of the isolated brain perfusion may be used in experiments with other isolated organs and in studies of toxic effects of oxygen.

[Electrophysiological features (EEG) of ethanol withdrawal syndromes on isolated perfused rat brain].

On isolated rat brains we studied native EEC and its derivates (mean EEC amplitude and power spectrums - Fourier transformation) during perfusion with ethanol (65 Mm/ L) and after its withdrawal. Previously rats were undergone ethanol burden for 6 days according to Majchrowicz procedures to get alcohol withdrawal syndrome. Duration perfusion without ethanol was 5, 10 and 20 min depending on the experimental schedule. Ethanol infusion between periods of withdrawal comprised 20 min. 55% of isolated brains shown epileptiform activity after 1-2 min of ethanol withdrawal but others manifested only increased mean amplitude and the power spectrums of EEC as well as an appearance of single or batch spikes. Differences between in vivo and in vitro conditions can be explained by the accelerated rate of ethanol elimination. The high positive correlation was obtained between EEC findings at the 5-th min of the first ethanol withdrawal and the same findings at the 5-th min of ethanol withdrawal in the second and the third episodes of ethanol withdrawal. Prolongation of withdrawal period more than 5th min caused brain death showing epileptiform activity. Isolated rat brain is the convenient subject to study pathogenesis of excitability of neurons and examination of drugs to treat alcohol withdrawal syndrome.

Significant entry of tubocurarine into the brain of rats by adsorption to polysorbate 80-coated polybutylcyanoacrylate nanoparticles: an in situ brain perfusion study.

The possibility of using polysorbate 80-coated polybutylcyanoacrylate nanoparticles to deliver low molecular polar hydrophilic drugs to the CNS has been studied. Tubocurarine (a quaternary ammonium salt) does not penetrate the normal intact blood-brain barrier. However, the injection of this drug directly into the cerebral ventricles of the brain provokes the development of epileptiform seizures as assessed by electroencephalogram (EEG). An in situ perfused rat brain technique was used as an experimental technique together with a simultaneous recording of the EEG. Nanoparticles were prepared by butylcyanoacrylate polymerization in an acidic medium. Fifteen minutes after the introduction of tubocurarine-loaded polysorbate 80-coated nanoparticles into the perfusate, epileptiform spikes in the EEG appeared. Intraventricular injection of tubocurarine caused the appearance of the EEG seizures 5 min after administration. Neither tubocurarine solution nor tubocurarine-loaded nanoparticles without polysorbate 80 or a mixture of polysorbate 80 and tubocurarine were able to influence the EEG. Thus only the loading of tubocurarine onto the polysorbate 80-coated nanoparticles appears to enable the transport of this quaternary ammonium compound through the blood-brain barrier.

[The role of ketone bodies in the development of postalcoholic-intoxication heart damage in rats]. / Issledovanie roli ketonovykh tel v razvitii postintoksikatsionnogo alkogol'nogo povrezhdeniia serdtsa u krys.

Experiments on rats subjected to forced alcoholization for 5.5 days were made to measure the content of ethanol, acetaldehyde and ketone bodies in the blood during intoxication and 2 days after ethanol withdrawal and to estimate the intensity of postintoxication disorders in heart activity on the third day after alcoholization withdrawal. A positive correlation was discovered between depression of left ventricular contractility and the blood content of acetaldehyde and ketone bodies. The magnitude of the threshold of heart fibrillation did not correlate well with the concentration of ethanol during alcoholization. However, it agreed well with ethanol concentration in the postintoxication period. Additional administration to the animals of beta-hydroxybutyrate or caprylic acid in the postintoxication period intensified heart contractility depression. The conclusion is drawn that elimination of ketosis in ethanol withdrawal as well as a progressive taking out of alcoholic patients from dipsomania can prevent the development or attenuate the intensity of postintoxication heart injury.

[Myocardial damage and the sympatho-adrenal system in ethanol abstinence syndrome in rats]. / Povrezhdenie miokarda i simpatiko-adrenalovaia sistema pri sindrome otmeny étanola u krys.

Increase in content of II-oxycorticosteroids and in activity of dopamine-beta-hydroxylase in blood serum, decrease in concentration of adrenaline in adrenal glands with simultaneous accumulation of the catecholamine in myocardium were observed in rats after intensive alcoholization within 5 days (intragastric administration of ethanol 4-5 g/kg twice daily). In this case content of noradrenaline and its density in the catecholamine-containing nervous fibers were decreased. Ethanol abolishing, as shown by dynamics of catecholamines in heart and adrenal glands, caused an additive stimulation of the sympathoadrenal system, which reached the maximal level within a day and accomplished within 3 days after the last ethanol injection. Abolishing of ethanol led to an increase in the rate of creatine kinase elimination from isolated perfused heart and to activation of the enzyme in rat blood, which reached the maximal value within 3-7 days after the last injection of ethanol. Development of myocardium impairments correlated with accumulation of catecholamines in extraneuronal structures of heart tissue.

[Experimental study of the effect of rubidium on the cardiovascular system]. / Eksperimental'noe issledovanie deistviia na serdechnososudistuiu sistemu.

The experimental data on the chronic inhalation effects of rubidium on the myocardium and the rate of natural organism aging are presented. No cardiotoxic effect of rubidium sulfate has been established. Hypotensive effect is associated with neurohormonal shifts at the level of an integral organism. Its impact does not result it potassium displacement in cells. Rubidium standardization should be carried out without taking account of gerontogenic effect.

[Cardiac effects of insulin in ethanol intoxication and in the postintoxication period]. / Kardial'nye éffekty insulina pri intoksikatsii étanolom i v postintoksikatsionnyi period.

Insulin (2 IU/ml) effect on the contractile function, glucose consumption and lactate release by the myocardium was studied in experiments on the isolated rat heart performed at different time after a single (8 g/kg) and 10-fold with a 12-hour interval (8-10 g/kg) intragastric administration of ethanol. A single administration of ethanol failed to influence the contractile function, glucose consumption and lactate release by the isolated heart. The magnitude of a positive inotropic reaction to insulin increased and its stimulating effect on glucose utilization by the myocardium weakened. The reaction of ethanol withdrawal developing after its 10-fold administration led to a disturbance of the contractile and rhythmic functions of the heart and activation of glycolysis. The heart inotropic reaction to insulin in this period weakened and glucose consumption and lactate release stimulated by insulin did not differ from control. During perfusion of intact rat hearts with and without glucose insulin (2 IU/ml) weakened the cardiodepressive effect of ethanol (200 mM).

[Contractile function, glucose consumption and lactate release by the isolated rat heart during different regimens of alcohol administration and after discontinuation of ethanol]. / Sokratitel'naia funktsiia, potreblenie gliukozy i vysvobozhdenie laktata izolirovannym serdtsem krys pri raznykh rezhimakh alkogolizatsii zhivotnykh i posle otmeny étanola.

Acute or chronic intoxication of rats with ethanol (intragastric administration at a dose of 8 g/kg or free-choice drinking of 10% ethanol for 3 months) produced no significant changes in contractile function, glycogen content, glucose uptake and lactate release in isolated hearts. Withdrawal syndrome simulated in rats following a short period of severe intoxication with ethanol at a dose of 4-5 g/kg twice daily has demonstrated a 15 and 28% decrease in peak systolic pressure and tension time index, respectively. In this case glucose uptake and lactate release were 2 times higher. Changes in glycogen level were observed three days after the last ethanol administration. The rats, survived after the abstinence period, revealed areas of perivascular myocardial necrosis. It is concluded that withdrawal syndrome plays an important role in pathogenesis of alcoholic cardiomyopathy.

[Relationship of the activity of cardiac cholinergic mechanisms to the state of the sympathetic innervation and its noradrenaline content in hypoxia]. / Zavisimost' deiatel'nosti kholinergicheskikh mekhanizmov serdtsa ot sostoianiia simpaticheskoi innervatsii i soderzhaniia v nem noradrenalina pri gipoksii.

Preliminary sympathectomia depletes acetylcholine (ACh) in the heart of rabbits under hypoxia. In these conditions the inhibitory action of ACh on the rat isolated heart is reduced under the noradrenaline content fall, while under increase it is potentiated. Under hypoxia noradrenaline increases concentration of potassium in the myocardium, thus stimulating ACh formation and activity. It is suggested that under deep hypoxia suppression of the sympathetic mechanisms causes functional isolation of the heart from nervous effects.