Biomedical subjects

R Nikolov

Publications and source records attributed to R Nikolov.

At least 55 records · Page 3Linked to original sources

PubMed1983

Study on the anti-hypoxic effect of some drugs used in the pharmacotherapy of cerebrovascular disease.

The anti-hypoxic effect of some agents used in the pharmacotherapy of cerebrovascular disease was studied using the following methods: incomplete ischemia by bilateral carotid ligation in rats, anoxic hypoxia by inhalation of argon in mice, and hemic hypoxia induced by injection of sodium nitrite (120 mg/kg s.c.) in rats. The following drugs were studied: piracetam, orotic acid, centrophenoxine, pentobarbital, vincamine, vinpocetine, cinnarizine, aligeron, xanthinol nicotinate and papaverine. The most pronounced anti-hypoxic effect was shown primarily with the metabolic acting drugs, such as orotic acid, centrophenoxine, piracetam and pentobarbital, followed by the preparations with combined metabolic and vasoactive properties (vincamine and vinpocetine). The predominantly vasoactive drugs were less effective in anoxic hypoxia, but showed more pronounced effect in incomplete ischemia.

Animals↗

PubMed1983

Effect of piracetam in some models of general and local depression of the cortical bioelectrical activity in cats.

The effect of piracetam (100 mg/kg i.v.) on general and local depression of the cortical bioelectrical activity was studied in acute experiments on cats. Asphyxic anoxia and hypoventilation hypoxia were used as models of general depression. Local depressions were caused by topical application of potassium chloride (KCl), adenosine monophosphate (AMP) and pentobarbital on the cortex. In the models of general depression piracetam increased cortical resistance to hypoxia and accelerated the recovery of the cortical bioelectrical activity. In KCl- and AMP-induced depressions piracetam diminished their degree and duration and completely protected the cortex against pentobarbital-caused depression.

Adenosine Monophosphate↗

PubMed1982

1,4-Benzodiazepines. VIII - Central depressive activity and spasmolytic action of isoquino-[2,1-d] [1,4] benzodiazepines. Structure-activity relationships.

The pharmacological activity of four new groups of isoquino [2,1-d] ((1,4]benzodiazepines, i.e. the 6-oxo-12,13-dimethoxy-5H-7H--9,10-dihydroisoquino [2,1-d] [1,4]benzodiazepinium bromides (I); 5,9,10,14b--tetrahydroisoquino [2,1-d] [1,4]benzodiazepin-7H-6-ones (II); 6-phenyl-12,13--dimethoxy-7,9,10,14b-tetrahydroisoquino [2,1-d] [1,4]benzodiazepines (III) and 6-phenyl-12,13-dimethoxy-7H-9,10-dihydroisoquino [2,1-d] [1,4]benzodiazepinium bromides (IV) was studied. All the compounds studied are biologically active. They show a depressive effect on the central nervous system, which is most pronounced in (II). It was established that the presence of alkyl substituents in the position-7 of the structure (II) as well as the chlorine atom in position-2 resulted in an increase of activity. Most of these compounds possess a mild or strong antinociceptive effect. Some of them exhibited an antireserpine activity as well. The spasmolytic effect of (IV) was strong while the rest of the compounds exerted a very weak spasmolytic effect. All the compounds tested on the autonomous nervous system possess the characteristics of weak sympathomimetics.

Animals↗

PubMed1982

Anti-hypoxic effect of prostacyclin.

The anti-hypoxic effect of prostacyclin (PGI2) was studied using the following methods: hypoventilation hypoxia and hypovolemic oligemia in cats and hypobaric hypoxia and complete ischemia by decapitation in mice. In experiments on cats PGI2 (250 ng/kg/min i.v.) led to an improvement of hypoxia-impaired EEG activity. In hypobaric hypoxia, PGI2 at all doses applied (50-500 micrograms/kg) led to a significant increase in the survival time (from 67.5% to 196%). In complete ischemia by decapitation, PGI2 at doses from 50 to 500 micrograms/kg significantly prolonged the gasping movements (from 7.8% to 20.6%). Different mechanisms of the anti-hypoxic effect of PGI2 are discussed. The effect observed would be potentially beneficial in hypoxic and ischemic states.

Animals↗

PubMed1982

Effect of prostaglandin F2 alpha and prostacyclin on asphyxic anoxia in cats.

The effects of exogenously applied prostaglandin F2 alpha (PGF2 alpha) and prostacyclin (PGI2) on asphyxic anoxia was studied in curarized and artificially ventilated cats. Anoxia was induced by stopping the ventilation and checking the changes in the EcoG. Cortical resistance (CRs) was evaluated as time between stopping the ventilation and the extinction of ECoG. Cortical recovery (CRc) was expressed as time between restitution of ventilation and reappearance of brain activity. Anoxia resistance index (ARI) was defined as the ratio between these two parameters (CRs/CRc). PGF2 alpha was applied by 5 minute i.v. and intracarotid (i.c.) infusion in a dose of 10 micrograms/kg/min, and PGI2 in a dose of 250 ng/kg/min for 15 minutes intracarotidly. The results show that both the i.c. and i.v. infusion with PGF2 alpha led to a significant decrease of CRs and prolongation of CRc resulting in decrease of ARI. The changes are more expressed at i.v. infusion, PGI2 does not improve the ECoG changes evoked by hypoxia. Suggestions for the possible mechanism of PGF2 alpha action and for the failure of PGI2 to protect the brain are made.

Animals↗

PubMed1982

Effect of orotic acid on the excitability processes in central nervous system and on cerebral circulation in cats.

The influence of orotic acid on cortical excitability processes and cerebral circulation was studied in acute experiments in cats. The effect on CNS excitability was assessed by examination of the cortical visual-evoked potentials and the recovery cycles. The flash-evoked responses were recorded from visual cortex (VC), associative cortex (AsC) and auditory cortex (AuC). The recovery cycles were determined as the ratio of the average response to the test stimulus and those to the conditioning stimulus depending on the interstimulus interval duration. For investigation of cerebral circulation the method of local cerebral rheoencephalography (REG) was used. The following REG parameters were assessed: amplitude, anacrotic sections of the curve and its relative part, and duration of the wave. The arterial blood pressure was monitored continuously. Orotic acid administration (50 mg/kg i.v.) induced a significant increase in the amplitude of the primary response from VC and AsC. Significant shortening of the peak latency of the second wave of the response in the VC was also observed. The recovery cycles examination showed a facilitation of the test response. The changes observed indicate an increase of excitability processes in the CNS. The REG changes after orotic acid indicate a cerebrovascular resistance decrease and increase in cerebral blood volume. It is assumed that increased cortical activity by orotic acid may lead to an improvement of cerebral circulation.

Animals↗

PubMed1981

[Antihypoxic action of orotic acid].

The authors examined the effect of the ortonic acid in comparison with several preparations from various pharmacologic groups on models of complete ischemia, obtained by decapitation and hypobaric hypoxia in mice. The ortonic acid showed strong anti-hypoxic effect in these two models. The results revealed that the strongest effect manifested the ortonic acid, followed by vinponcetine and cinarizine, in mice with hypoxia, induced by decapitation and by the method of hypobaric hypoxia. Hexobarbital-sodium and papaverine showed comparatively weaker effect, but xantional nicotinate - the slightest. A wide spectrum od drugs, known by experimental and clinical data as antihypoxic drugs allowed the authors to accept the models as relative and the conclusion for the effect of the ortonic acid was considered as significant. They assume that vascular and metabolism effect participates in the mechanism of the antihypoxic action of the ortonic acid.

Animals↗

PubMed1981

The effect of lonetyl on the electroencephalogram and rheoencephalogram of experimental animals.

In view of the interesting problem of the correlation between the functional cerebral activity and cerebral blood circulation, as well as the controversy in the literature concerning the effects of tranquilizers on cerebral blood circulation, the effects of the daily tranquilizer Lonetyl on the spontaneous cerebral bioelectrical activity and cerebral haemodynamics have been studied. According to rheoencephalographic data, Lonetyl is found to reduce cerebral vascular tone, which is manifested by decreased values of the relative share and the dicrotic index, the maximum effect being observed between the 15th and 30th min. The changes in the EEG consist in significant increase of the alpha- and theta-activity, with maximum effect on the 15th min, increased mean frequency and decreased mean amplitude. Synchronization of the cerebral bioelectrical activity is observed after the 30th min.

Animals↗

PubMed1980

Experimental rheoencephalographic and electroencephalographic investigations on piracetam.

The influence of piracetam (2-oxo-1-pyrrolidine-acetamide, Pyramem) on the cerebral circulation and brain bioelectrical activity of cortex and mesencephalic reticular formation (RF) was studied in acute experiments on cats which were encéphale isolé preparations. The methods of local cerebral rheoencephalography (REG) and electroencephalography (EEG) were used. The following REG parameters were assayed: anacrotic section of the curve and its relative part, amplitude and duration of the wave. The arterial blood pressure was followed continuously. The results show that upon piracetam administration (150 mg/kg i.v.) an improvement of the REG parameters of the cortex and RF is observed-an increase of the amplitude and decrease of the values of the anacrotic section of the curve and its relative part. The changes observed indicate a cerebro-vascular resistance decrease and give indirect evidence of cerebral blood volume increase. EEG data are characterized mainly by an increase of alpha-waves, both of cortex and RF. Suggestions for possible mechanism of action of piracetam are made.

Animals↗

PubMed1980

The effect of piracetam on the local cortical cerebral blood flow in cats.

The effect of piracetam (2-oxo-1-pyrrolidine-acetamide, Pyramem) on the local cortical cerebral blood flow (CBF) and oxygen balance in the brain was studied on cats anesthetized with ether-chloralose. The changes in local CBF were registered by means of the thermistor thermoclearance technique. pO2 and pCO2 were determined in blood samples from the femoral artery and superior sagittal sinus and arterio-venous differences of O2 and CO2 partial pressures (AVD-O2 and AVD-CO2) were calculated. The experiments were made on normoxic animals and on animals with slight hypoxia. Piracetam administration (100 mg/kg i.v.) leads to an increase in local cortical CBF corresponding to a change in the specific thermoconductivity of the brain of 0.6 . 10(-4) cal . cm-1 . sec-1 . degrees C-1. This effect is observed in 84% of the experiments with normoxia (arterial pO2 96.0 +/- 21.0 mm Hg) and in 40% of the experiments with slight hypoxia (arterial pO2 59.9 +/- 6.0 mm Hg). Changes in AVD-O2 and AVD-CO2 are not observed. Most probably the increase in CBF does not participate in the mechanism of the protective action of piracetam in hypoxia.

Animals↗

PubMed1980

Effect of prostaglandins F2alpha and E1 on local tissue Po2 and microflow of the brain cortex (cat).

The effects of prostaglandin F2 alpha (PGF2 alpha) and E1 (PGE1) on local tissue Po2 and microflow in the cat's brain surface were studied. Local tissue Po2 was polarographically measured with a multiwire surface electrode, and microflow measured by local hydrogen clearance method. The PGs were investigated by intracarotid (i.c.) infusions, single i.c. and intravenous (i.v.) injections. The i.c. infusions were made with dose of 3, 10 and 30 microgram/kg/min of PGF2 alpha and 0.1, 0.4 and 1.0 microgram/kg/min of PGE1. The i.c. application of PGF2 alpha led to a decrease in local tissue Po2 and tissue microflow. With the use of comparatively low doses (3 and 10 microgram) the effect appeared to be more specific, since SAP did not change significantly. Systemic (i.v.) injections of PGF2 alpha caused a significant drop in arterial pressure and decrease in tissue Po2. Studies with PGE1 always demonstrated a decrease in local tissue Po2 and microflow associated with a significant decrease in the SAP. No evidence for a specific effect was found. Suggestions for possible mechanism of action for these PGs are made.

Alprostadil↗

PubMed1980

Effect of aligeron on the resistance of the cerebral and peripheral blood vessels.

The effect of the cinnarizine analogue Aligeron on the resistance of cerebral and peripheral blood vessels was studied in acute experiments on cats and dogs. The resistance of the cerebral vessels was determined directly and indirectly. For direct determination the method of autoperfusion was used. The resistance was calculated indirectly as a quotient of mean arterial blood pressure and internal carotid blood flow. For evaluation of Aligeron effect on the resistance of the peripheral blood vessels and method of autoperfusion of the femoral artery was used. Aligeron was administered i. v. and i. a. In some of the experiments the compound was applied on the background of previously injected dihydroergotamine. Cinnarizine and papaverine were used as reference compounds. The results show that Aligeron decreases considerably the cerebral and peripheral resistance vessels tone, and its effect is higher than those of cinnarizine. For the realization of this effect most probably its direct myotropic action plays the main role. The reduction of its effect after alpha-adrenergic blockade suggests an involvement of some adrenergic blocking properties in its mechanism of vascular action.

Animals↗

PubMed1980

[Effect of prostaglandin F2 alpha on the cerebral circulation in cats].

The author examined the influence of prostaglandin F2 alpha 2 (PgF 2 alpha) on the cerebral circulation in cats by means of polarographic method. He measured the local tissue tension of oxygen in the cerebral cortex (PO2) with the help of multiple wire superficial electrode. PgF 2 alpha was administered under the form of 5-minute infusions in the carotid artery in a dose of 3 and 10 mkg/kg/min. The intracarotid administration of PgF 2 alpha caused statistically significant reduction of PO2 in the cerebral cortex but the dose of 3 mkg/kg/min did not alter the arterial blood pressure significantly. The increase of the dose did not enhance the effect as the blood pressure was lowered significantly. He discussed the possible mechanisms of effect on PO2 in the cerebral cortex under the influence of PgF 2 alpha.

Animals↗

PubMed1980

Experimental studies on the effect of Aligeron on the cerebral circulation.

In acute experiments on cats under urethan anaesthesia and on dogs under chloralose-urethan narcosis the effect of the cinnarizine analogue Aligeron on local cortical cerebral blood flow (local CBF) and internal carotid blood flow was studied. The local CBF was recorded by means of a thermoclearance method using thermistor transducers. In addition the cortical pH and the arterial blood pressure were registered. For determination of internal carotid flow the flowmetric method was used accompanied by a simultaneous registering of heart rate and arterial blood pressure. Cinnarizine and papaverine were used as reference compounds. The results obtained show that Aligeron increases both the internal carotid flow (with 64% in a dose of 5 mg/kg) and the local CBF (with 30% in a dose of 1 mg/kg and 40% at 5 mg/kg). This effect is higher and longer-lasting than those of cinnarizine and papaverine.

Animals↗

PubMed1980

[Effect of aligeron and cinnarizine on the behavior of experimental animals].

The following methods were used: neuropharmacologic study according to the a modified method of Nikolova, Daleva, orientation reaction according to Boissier and Simon, "open field" according to Fontenay et al. and actographic study. The data from "the free" observation suggested clearly a manifested central stimulating effect of aligeron. The data from the actographic study were similar, which showed an increased motor activity in mice and rats, given doses of 1/100-1/4 of LD50. The stimulating action of the preparation was observed in doses of 1/8-1/6 of LD50 during the experimental procedure "open field". The preparation inhibited orientation reaction in mice. Cinnarizine inhibited the examined indices, obtained by all tests. The complex of the used methods allowed to make an inference that aligeron had central stimulating effect, weaker in smaller therapeutic doses and more manifested in higher doses. Cinnarizine had weak depressive effect.

Animals↗

PubMed1979

Scintigraphic and radiocirculographic studies on the effect of As2 on cat cerebral circulation.

Various well-known agents with a favourable influence on cerebral circulation were used as a basis for creating new methods to asses the effects on this vascular region in experimental animals. A technique was worked out for radiocirculography and simultaneous radiometry, as well as for scanning and simultaneous radiometry of cat brain. Radiocirculography, followed by scintigraphy, proved to be among the best methods used for assessment of the effect of As2 on cerebral circulation. Simultaneous radiometry with the methods mentioned above had only orientational value. Radiocirculographic and scanning data after application of As2 in a dose of 10 mg/kg are close to those for nicotinic acid in a dose of 1 mg/kg. Similar to the data of the isotopic methods after application of As2 in a dose of 5 mg/kg are the results obtained with 5 mg/kg cinnarizin, which suggests a similar machanism of action.

Animals↗

PubMed1979

Experimental rheoencephalographic studies on the effect of the cinnarizin analogue As2 on cerebral circulation.

The effect of As2 and Cinnarizin on cerebral circulation is studied on rabbits using the method of local cerebral rheography. Rheoencephalograms (REG) are recorded from the following brain structures; sensomotor cortex, substantia alba, poseterior hippocampus amygdala; nucleus caudatus and coliculus superior. Arterial blood pressure and ECG are studied simultaneously. Qualitative and quantitative analysis of the REG wave is made. Quantitative analysis involves the calculation of the following parameters: amplitude, anacrotic section of the curve and its relative part, spreading time and dicrotic index. The complex of REG-changes under the effect of the two drugs is very similar and suggests dilatation of the cerebral blood vessels. The difference is in the time of occurrence of the maximum effect: 5th min for As2 and 45th min for Cinnarizine.

Animals↗

PubMed1979

Simultaneous investigation of the cerebral circulation and cortical bioelectrical activity in dogs under the influence of piracetam.

By means of the methods of local cerebral rheoencephalography (REG) and electroencephalography (EEG) the effect of piracetam (1-acetamide-2-pyrrolidone, Pyramem) on cerebral circulation and brain bioelectrical activity was studied in acute experiments on dogs. The following REG parameters were assayed: anacrotic section of the curve and its relative part, amplitude and dicrotic index. The influence of the preparation on the spontaneous EEG was studied by means of surface electrodes, pH, pO2, and pCO2 were determined in blood samples from femoral artery and superior sagittal sinus and arterio-venous differences of O2 (AVD-O2) and CO2 (AVD-CO2) were calculated. The arterial pressure and ECG were followed continuously. The results showed that after piracetam administration (100 mg/kg i.v.) an improvement of the REG parameters is observed: increase of the amplitude and decrease of the values of the relative part and dicrotic index. The changes observed indicated cerebro-vascular resistance decrease and increase of the cerebral blood volume. The AVD-O2 increased and the negative AVD-CO2 decreased. The EEG data indicated an improvement in the functional state of the brain cortex. Suggestions as to mechanism of piracetam effect and the usefulness of the methods were made.

Animals↗