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Biomedical subjects

O S Medvedev

Publications and source records attributed to O S Medvedev.

At least 19 recordsLinked to original sources
PubMed1995

Allopurinol: kinetics, inhibition of xanthine oxidase activity, and protective effect in ischemic-reperfused canine heart as studied by cardiac microdialysis.

With microdialysis, we monitored cardiac interstitial fluid (ISF) levels of allopurinol, its metabolites, and the adenine nucleotide breakdown products (ANBP), inosine, hypoxanthine (HYP), xanthine (Xa), uric acid (UA) in dogs that received 1 and 10 mg/kg allopurinol intravenously (i.v.). Half-life (t1/2) of drug penetration into the heart was dose independent (1.8 min), whereas for the 10-mg/kg dose terminal elimination t1/2 (96 min) was much prolonged and ISF clearance (9.6 l/min kg) was reduced as compared with that induced by 1 mg/kg (28 min and 30.4 l/min kg) probably due to capacity limitation of allopurinol conversion to oxypurinol by Xa dehydrogenase/oxydase (Xa D/O). Inhibition of Xa D/O activity by allopurinol resulted in a dose-dependent increase in ISF HYP and Xa levels and a decrease in UA level. For a 10-mg/kg dose, maximal effect was attained approximately 40 min after drug injection. Allopurinol (1 mg/kg) given 30 min after the start of 40-min coronary artery occlusion during ischemia entered the ischemic zone ISF very slowly as compared with that of the control zone; the no-reflow phenomenon was evident because the levels became similar in both zones only 15 min after initiation of reperfusion. To examine cardioprotective efficiency, we administered allopurinol (10 mg/kg) 40 min before 40-min occlusion; it had little effect on total ANBP release during ischemia but facilitated washout of ANBP from the ischemic zone during reperfusion, thus manifesting protective efficacy against reperfusion injury and no-reflow. As shown by the lack of ischemia-induced increase in ISF Xa, myocardial Xa D/O activity was completely blocked by allopurinol.

Adenine Nucleotides↗
PubMed1992

Cardiac microdialysis measurement of extracellular adenine nucleotide breakdown products during regional ischemia and reperfusion in canine heart: protective effect of propranolol against reperfusion injury.

Using cardiac microdialysis, we studied release of the adenine nucleotide breakdown products (ANBP) adenosine (ADS), inosine (INS), and hypoxanthine (HYP) into the interstitium of canine myocardium during 20- and 40-min occlusion of the anterior descending coronary artery and reperfusion. Dialysate ANBP concentrations reached maximum values not at the end of ischemia but in the first 10 min of reperfusion. The effect was more pronounced after 20-min ischemia. Further reperfusion led to an ANBP decrease that was more prolonged after 40-min ischemia. Pretreatment with DL-propranolol (0.5 mg/kg, intravenously, i.v.) given 40 min before coronary occlusion had no effect on adenine nucleotide catabolism rate during 20- and 40-min ischemia, but it facilitated washout of ANBP from ischemic zone immediately after the start of reperfusion. A similar effect was elicited by a D-stereoisomer of propranolol with no beta-adrenoceptor blocking activity. Results suggest that the reperfusion injury and probably the no-reflow phenomenon were the cause of enhanced adenine nucleotide catabolism at the beginning of reperfusion and prolonged ANBP washout from the ischemic zone. Reduction of reperfusion injury by propranolol could be related to the membrane stabilizing and antioxidant activity of this agent. Examination of DL-propranolol kinetics in arterial and coronary venous blood plasma showed that drug accumulation in the myocardium was almost maximum at the start of ischemia; therefore, the efficiency of cardio-protection with DL-propranolol was not limited by pharmacokinetic causes. Insertion of an additional microdialysis probe in the myocardium allowed monitoring of extracellular propranolol concentrations.

Adenine Nucleotides↗
PubMed1992

[The hemodynamic and metabolic effects of 2-deoxy-D-glucose in waking Wistar rats].

The effect of 2-deoxy-D-glucose (2-DG) in a dose of 250 mg/kg as a stressogenic factor on changes in hemodynamic parameters and metabolism in awake rats was quantified during 6 hours. It was found that a single 2-DG injection causes lowering of blood pressure on min 40 and 120. Heart rate tended to slow down. Diminished glucose concentration in the brain observed on experiment minute 15 induced a number of adaptive reactions in the body. Epinephrine plasma levels increased sharply on min 15 and 40. Norepinephrine concentrations elevated slightly only at the beginning of the experiment. The maximal glucose level in blood plasma was observed on min 40 and 120 and that of lactate 40 min following 2-DG injection. The level of immunoreactive insulin rose. Glucose content in the heart came up sharply on min 15 and 40. Lactate concentration in the heart increased continuously.

Animals↗
PubMed1992

[Two-phase effect of endothelin-1 on resistance of coronary vessels in anesthesized rats with intact chest].

Effects of intracoronary infused (2 pM/kg/min for 5 min) endothelin-I on coronary blood flow was studied using modification of the method of Vetterlein and Schmidt. Blood flow in extracorporeal circuit was measured by 20 MHz pulsed Doppler flowmeter. One end of the circuit was connected to the left common carotid artery and the other was connected to the especially curved glass cannule which was placed to the origin of the coronary artery and through the right common carotid artery. Five-minute infusion of endothelin was followed by transitory dilatation and then by constriction of coronary vessels. Blockade of dihydropyridine-sensitive Ca-channels potentiated endothelin-induced vasodilation and decreased the constrictor response three-fold.

Animals↗
PubMed1992

[Parameters of systemic hemodynamics in conscious rats with acute streptozotocin diabetes].

The effect of acute streptozotocin-induced diabetes mellitus on the systemic hemodynamic parameters was studied in conscious rats by thermodilution technique. Male Wistar rats were made diabetic with a single intravenous injection of streptozotocin (STZ, 50 mg/kg). The most important finding of this work was the elucidation of the systemic vasodilation and increased cardiac index one day after STZ injection. Such alteration in hemodynamic parameters could result in the increased blood flow and capillary hypertension in some vascular beds and, therefore, be considered as a pathogenic factor in the development of diabetic microangiopathy.

Acute Disease↗
PubMed1992

[Effects of taurine and dipeptide Tyr-Tyr on ventricular defibrillation].

Results of the study of taurine and dipeptide Tyr-Tyr effect on the threshold values of functional lesions of the myocardium and heart defibrillation are reported. The experiments were carried out on 27 narcotized mongrel dogs weighing 12-30 kg. Defibrillation was performed using Lifepak-7 defibrillator (USA). Lesion threshold (LT), defibrillation threshold (DT) and electrotherapeutic index (ETI) as a LT:DT ratio were determined. In 14 experiments (control group) these parameters were evaluated during 3 h. In group 1 (6 experiments) taurine (100 mg/kg) was infused intravenously by the end of the 1st hour, in group 2--Tyr-Tyr (25 mg/kg). It was shown that infusion of taurine did not have a noticeable effect of the LT, DT and ETI values. Infusion of Tyr-Tyr resulted in an increase in LT and DT. The possibility to use dipeptide Tyr-Tyr in the complex of measures aimed at ceasing ventricular fibrillation is discussed.

Animals↗
PubMed1991

[The cardiovascular effects of endothelin in waking rats with normal and artificially increased atriopeptide levels of the blood].

The systemic and regional hemodynamic effects of endothelin: a new vasoconstrictor peptide, were studied in alert WKY rats. The radioactive microsphere technique was used to measure cardiac output, total peripheral resistance and regional blood flow before and 10 min after bolus injection of endothelin into the left ventricle. Endothelin produced a transient hypotension followed by a long-lasting increase in blood pressure and in systemic resistance and a decrease in cardiac output. Endothelin induced a decrease in blood flow in all vascular beds to variable extent (the maximal changes were recorded in kidneys and adrenals), only the coronary blood flow being increased. In the rats receiving constant atriopeptine II infusion, the hypotensive phase of endothelin effects was augmented whereas the hypertensive phase was reduced. Atriopeptine II infusion also diminished the regional blood flow responses to endothelin in the kidneys, the adrenals and the heart.

Animals↗
PubMed1991

[Differences in the redistribution of cardiac output during hyperthermia in waking rats and guinea pigs].

The heat stress induced common responses in rats and guinea pigs: an increase in the blood flow at the sites of heat radiation and in the diaphragm, and its decrease in splanchnic area's organs and in kidneys while cardiac output remained constant. The species differences occurred in the responses of intestine and skeletal muscles' vessels. The differences seem to be due mainly to the differences in behavioral responses to the heat stress in these animals.

Animals↗
PubMed1991

[The cardiovascular reactions during audiogenic seizures in rats genetically predisposed to epilepsy].

Changes in arterial pressure (AP) and venous tone were studied in Krushinskiĭ-Molodkina (KM) rats genetically predisposed to audiogenic seizure, during the audio stress and 20 min after it. The venous tone was estimated by the mean circulatory filling pressure (MCFP) during a short arrest of circulation by inflating a balloon in the right atrium. It was shown that, during seizure, AP raised from 104 to 156 mm Hg on the average, while MCFP decreased from 8.9 to 7.4 mm Hg. Ganglion blockade with hexamethonium did not prevent the development of pressor reaction during seizure. The intensity of subdural and subarachnoidal hemorrhagic correlates with the raise of AP during seizure. The hemorrhagic area spread over 75 mm2 during AP greater than 200 m Hg, while in lower increment it was only 2.56 mm2. The KM rats can be used in experimental modelling of brain circulation disorders caused by acute increase in AP.

Acoustic Stimulation↗
PubMed1991

[A microdialysis study of noradrenaline release in the hypothalamus evoked by 2-deoxyglucose in waking rats].

Intracerebral microdialysis was used to examine extracellular concentrations of noradrenaline (NA) in the lateral hypothalamus of alert rats. Desipramine (0.01 mmol) added to the perfusion medium did not change basal NA release. 2-deoxyglucose-induced (500 mg/kg) neuroglycopenia led to an increase in extracellular NA in hypothalamus which reached maximum 10-30 min after drug administration.

Animals↗
PubMed1991

[Study by the intracerebral microdialysis method of the effects of atypical neuroleptics and anxiolytics on striatal release and metabolism of dopamine in awake rats].

Using brain microdialysis in awake rats effects of risperidone, ritanserin, buspirone, sulpiride and 5-methoxy-N,N-dimethyltryptamine (MeODMT) on striatal dopamine (DA) release and metabolism were studied. Risperidone, sulpiride and buspirone increased levels of DA, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA). Ritanserin failed to affect DA release, while increased DOPAC and HVA levels. MeODMT had no effect on striatal DA release and metabolism. Possible interaction between DA and serotonin systems is discussed.

Animals↗
PubMed1991

[Systemic and regional hemodynamics during audiogenic convulsions in rats genetically epilepsy-prone].

Changes in systemic and regional hemodynamic during sound-induced convulsions were measured with microsphere technique in genetically epilepsy-prone rats of Krushinsky-Molodkina (KM-rats) strain. Blood pressure increased from 103 till 178 mm Hg and cardiac index rose from 27.3 till 49.3 ml/min/100 g b. w. during convulsions. Blood flow was increased in the brain and in the heart by 140-700%, whereas in most of internal organs it was decreased by 40-94%.

Animals↗
PubMed1991

[Increased sensitivity of the cardiovascular system to captopril after microsphere embolization of the coronary vessels].

Changes in captopril sensitivity as a result of coronary embolization by 15 um microspheres were studied in rats. Selective coronary embolization was produced by injection of microspheres into the left ventricle during ascending aorta occlusion. The hemodynamic data were examined in conscious rats 21 days after embolization or sham operation before and after captopril bolus injection (1 mg/kg) by using microspheres method. Captopril injection caused a significant increase of the blood flow in the heart, kidneys, skin and some intestinal organs.

Animals↗
PubMed1991

[Disordered sympathetic regulation of the functions of the cardiovascular system in rats with streptozotocin diabetes].

The effect of sympathomimetic tyramine on the systemic and regional hemodynamic parameters was studied by the radioactive microsphere technique in experiments on conscious streptozotocin-diabetic and age-matched control rats. The dose of tyramine required for blood pressure elevation on 15-20 mm Hg was 5.6 times as large in diabetic rats as compared to control animals. It was suggested that sympathetic neuropathy may play the role in the development of the cardiovascular alterations in streptozotocin-diabetic rats.

Amphetamine↗
PubMed1991

[Systemic and regional hemodynamic reactions to metabolic stress caused by 2-deoxyglucose].

Changes in parameters of systemic and regional hemodynamic, elicited by intraarterial administration of 250 or 500 mg/kg of 2-deoxy-D-glucose (2-DG) were studied in the awake Wistar rats with microsphere technique. Measurements were performed before, 15-and 40-min after 2-DG administration. Significant decrease in the heart rate as well as increase in stroke volume were observed 15 min after 2-DG. It was a tendency to increase in cardiac output. Blood flow in skin and skeletal muscles were decreased whereas in the brain, heart, adrenal glands and small intestine there were significant increases in the blood flow. We conclude that hemodynamic responses to 2-DG reflect the effects of humoral (adrenaline) and central sympathetic factors.

Animals↗
PubMed1991

[Hemodynamic mechanisms of the hypotensive effect of cobalt in anesthetized rats].

Hemodynamic mechanisms of Co(2+)-evoked hypotension were studied in pentobarbital--anesthetised male Wistar rats. Bolus i.v. administration of cobalt sulphate (30, 90 and 270 mg/kg of Co) evoked dose-dependent hypotension followed by tachycardia and increase in left ventricular contractility index (dP/dt/P). Administration of beta-adrenoblocker propranolol (2 mg/kg) attenuated Co evoked (270 ug/kg) tachycardia and unmasked its cardiodepressive effects (dP/dt/P decreased by 11% and end-diastolic pressure increased by 55%). Cardiodepressive Co2+ effects were prevented by administration of verapamil (0.4 mg/kg). In the second group hemodynamic mechanisms of Co-evoked hypotension were studied with radioactive microspheres. Co2+ infusion (55 mg/kg) lowered blood pressure (in average by -11%) by decreasing total peripheral resistance (-25%). Cardiotoxic effects were obtained with a ++larger dose 80 mg/kg/min. It is concluded that Co decreased blood pressure by vasodilatator action and its cardiotoxic effects attenuated by sympathetic counterregulation and may be prevented by verapamil.

Anesthesia, General↗