Effect of selective blockade of M4 cholinoreceptors by tropicamide on blood supply in brain, splanchnic azygous organs, and hindlimbs in intact rats.

Experiments on anesthetized rats carried out with a high-frequency ultrasonic system and tropicamide, a highly selective blocker of M4 cholinoreceptors, showed that the vasodilator effects observed after selective blockade of M4 cholinoreceptors are not organ-specific. Intravenous tropicamide (0.1 µg/kg body weight) transiently decreased systemic BP, elevated the linear and volume fl ow rates, and diminished vascular resistance in common carotid, superior mesenteric, and femoral arteries. At the same time, in most rats (76%) the fl ow rate in the portal vein did not change, while in 25% rats it insignificantly and temporarily increased. The hypothesis on possible involvement of M4 cholinoreceptor structures in cholinergic vasoconstriction is discussed.

[Respiratory and cardiovascular responses to hypoxia under activation or blockade inhibitory transmission].

Respiratory rhythm changes and hypoxic ventilatory responses were studied in anesthetized albino rats after administration GABA and adenosine receptor antagonists. Intracisternal microinjection of picrotoxin induced pathological periodic breathing. Picrotoxin intravenous administration caused the increase of individual resistance to acute hypoxia. Aminophylline administration exerted the opposite effect. After pretreatment of hydroxybutyrate we observed different types of respiratory reactions to adenosine antagonist injection, which probably depended on the value of arterial blood pressure and cerebral hemodynamics.

Role of various subtypes of muscarinic cholinergic receptors in the development of posthemorrhagic abnormalities in systemic and portal circulation in rats.

The experiments employing high-frequency ultrasonic technique and selective blockers of M1, M3, and M4 muscarinic cholinergic receptors pirenzepine, 4-DAMP, and tropicamide, respectively, revealed individual roles of these receptors in the development of severe posthemorrhagic hypotension in rats with low or high individual resistance to circulatory hypoxia. The study showed that M1 and M4 muscarinic receptors are involved in shock-limiting and shock-activating processes, respectively, while M3 receptors exert no effect on the course of posthemorrhagic abnormalities in systemic and hepatic portal circulation and on the posthemorrhagic lifespan. Poor resistance of the cardiovascular system to circulatory hypoxia during shock development is considered to be dysregulatory pathology.

Spectral analysis of blood velocity fluctuations and characterization of the mechanisms controlling the tone of individual microvessels in frog tongue.

Intravital microscopy and high-frequency ultrasonic system equipped with a microtransducer working at 38.5 MHz were employed to record blood velocity in arterioles and venules in the symmetrical fragments of the microvascular bed in frog tongue. The diameters of the vasculature ranged 75-200 µ. The record length was 2-5 min. The range of blood velocities was wider in the left arterioles than in the right ones, and inversely, it was greater in the right venules than in the left ones. The high-frequency and respiratory harmonics (0.2-1.5 Hz) dominated in the velocity spectrum of microvessels at each side, the greatest values being 64.6 and 72.3% for the left venules and the right arterioles, respectively. The low-frequency harmonics (0.009-0.02 Hz) were rare observed (7.6-15.4% examined vessels). They appeared in vessels with pronounced difference between the maximum and minimum velocities, in the cases with velocity variations looking like batches (bursts), etc. Correlation of velocities in arterioles and venules was positive at the left side (0.451) and negative at the right side (-0.574) of the tongue.

[Hemodynamic mechanisms of negative impact of emotional stress on the development of cerebral ischemia in stressor load-sensitive rats].

Emotional stress aggravates the course of brain ischemia that has developed in the presence of the former. The investigation studied the functional state of parietooccipital leptomeningeal anastomoses by vital biomicroscopy, as well as the linear blood flow velocity in the a. cerebri media and a. basilaris by high-frequency (38.5 MHz) Doppler ultrasonography before and after occlusion of the common carotid artery in normal (control) Wistar rats and ones that had experienced 18-hour aggressively conflict emotional stress and that were sensitive to the latter. Hemodynamic differences were found in the rats having a varying sensitivity to the used model of cerebral ischemia. Inadequate collateral blood supply along the circle of Willis was shown when this model of brain ischemia was used in the control animals. It was ascertained that in emotional stress, blood flow considerably reduced in the a. basilaris; the contiguous blood supply area displayed evolving brain edema that compressed leptomeningeal anastomoses and prevented the formation of collateral circulation, followed by occlusion of the common carotid arteries. With this, unilateral occlusion was followed by a short-term reduction in systemic blood pressure (BP) that was not seen in the controls and bilateral occlusion was by the development of collapse. Cerebral blood flow became dependent of systemic BP. The obtained experimental data suggest that it is expedient to include antistressor agents into therapy for chronic cerebrovascular diseases. This is particularly relevant to patients with occlusive carotid artery lesion and Willis circle anomalies since emotional stress may be fatal to them.

[Mechanism of the effect of anti-angina drugs with adrenergic beta receptor agonist action on the collateral hemodynamics and redistribution of the blood flow in chronic myocardial ischemia]. / K mekhanizmu vliianiia antianginal'nykh sredstv s beta-adrenostimuliruiushchim komponentom deistviia na kollateral'nuiu gemodinamiku i pereraspredelenie krovotoka pri khronicheskoi ishemii miokarda.

The experiments on dogs showed that in chronic myocardial ischaemia nonachlasine raising the retrograde arterial pressure and increasing the retrograde blood inflow to the ischaemic focus exerts a positive influence on the collateral cardiac haemodynamics. Raising the tonus of the coronary vessels in the intact regions of the myocardium to a greater extent than in the ischaemic region, nonachlasine redistributes the bloodflow to the advantage of the ischaemic zone. Oxyphedrin, decreasing of the ischaemic zone. Oxyphedrin, decreasing the tonus of the coronaries, especially in the intact areas of the myocardium, elicits the syndrome of "stealing" the zone of ischaemia.

[Changes in the blood circulation in the middle cerebral and common carotid arteries of rats under the influence of flunarizine]. / Izmeneniia krovoobrashcheniia v srednei mozgovoi i obshchei sonnoi arteriiakh krys pod vliianiem flunarizina.

Experiments conducted on Wistar rats under general anesthesia using the Doppler ultrasonic method showed that flunarizine caused a slowly developing (for 20 min), moderate (25%), and prolonged (90 min) increase of the blood flow in the middle cerebral artery. In the common carotid artery the drug induced two-phase changes in blood circulation. The initial increase in the blood flow was replaced by its reduction below the basic level.

[Nimodipine, nifedipine and the cerebrovascular effects of serotonin]. / Nimodipin, nifedipin i tserebrovaskuliarnye éffekty serotonina.

Experiments on rats with the use of ultrasonic techniques demonstrated that serotonin causes an initial significant decrease in the blood flow in the channel of the middle cerebral artery followed by a mild increase in the blood supply to the brain. It was shown in in vivo experiments that nimodipine and nifedipine do not prevent the development of serotonin-induced constriction of the vessels of the middle cerebral artery channel. At the same time, the cerebrovascular effects of nimodipine and nifedipine are significantly weakened under the action of serotonin.

[Circulatory changes in the middle cerebral artery and the carotid arteries of rats under the influence of nifedipine]. / Izmeneniia krovoobrashcheniia v srednei mozgovoi i sonnykh arteriiakh krys pod vliianiem nifedipina.

The experiments on Wistar rats with Doppler ultrasonography [correction of echocardiography] have shown that nifedipine causes a substantial and longterm circulatory increase in the middle cerebral artery. With nifedipine, blood flow increases in the common and internal carotids to a lesser extent, the changes being less long, and outstrip the responses of cerebral vessels in time.

[Structure of hemodynamic responses in the central command to move]. / Struktura gemodinamicheskikh reaktsii pri tsentral'noi komande k dvizheniiu.

Cardiac and vascular components of the hemodynamic response to "central command" to the skeletal muscles in immobilized decerebrated cats using an experimental model of "fictitious scratching" revealed that activation of the m. gastrocnemius increased blood pressure by 57 mm Hg, whereas cardiac output and blood flow in the common iliac artery changed insignificantly. The maximal increase of the blood flow in common iliac artery depended mainly on the stimulation of beta-adrenoreceptors by circulating catecholamines. The adaptive cardio-vascular responses during "central command" to skeletal muscles seem to depend mainly on the elevation of peripheral vascular resistance, there being no specific vasodilator influences on blood vessels of the muscles receiving the "central command".

[Cardiovascular system in rats with varying resistance to acute hemorrhage]. / Serdechno-sosudistaia sistema u krys s razlichnoi ustoichivost'iu k ostroi krovopotere.

Ultrasonic and laser doppler flowmetry, biomicroscopy were used in the study of systemic hemodynamics, microcirculation, blood flow in the brain, liver, kidneys and inferior limb in rats varying by resistance to acute blood loss. In the course of bleeding both high- and low-resistant rats (HRR, LRR) had the same decline in blood pressure, blood flow rate and tissue perfusion. When blood loss stopped. HRR developed relative compensation of the above parameters followed by irreversible fall. Posthemorrhagic recovery of these hemodynamic parameters in LRR was not observed. All the LRR showed persistent generalized constriction of hepatic, intestinal and renal microcirculation. Pumping performance of the heart continued to death in all HRR and in 65% of LRR. After stop of hemorrhage, 35% of LRR developed minor cardiac ejection syndrome which was followed by death within 30 min.

[Changes in individual resistance of cardiovascular and respiratory systems of rats to posthemorrhagic hypoxia after pharmacological impact on brain function]. / Izmeneniia individual'noi ustoichivosti sistem krovoobrashcheniia i dykhaniia krys k postgemorragicheskoi gipoksii posle farmakologicheskikh vozdeistvii na funktsional'noe sostoianie golovnogo mozga.

In experiments on rats it was shown that injection to rats before hemorrhage of analeptic corasol or prior injections during three days of the inhibitory mediator sodium oxybutyrate decrease individual resistance of the respiratory and circulatory systems (arterial blood pressure, cardiac output, organ portal blood flow) to posthemorrhagic hypoxia. Injection to animals before the hemorrhage of GABA-A antagonist picrotoxin significantly raises individual resistance to massive bleeding. Individual resistance to acute hemorrhage correlates with individual sensitivity of cardiovascular and respiratory systems to corasol.

[Organ-specific characteristics of blood supply in the liver, kidney, and brain in acute blood loss in rats with various resistance to circulatory hypoxia]. / Organospetsificheskie osobennosti krovosnabzheniia pecheni, pochek i mozga pri ostroi krovopotere u krys s razlichnoi ustoichivost'iu k tsirkuliatornoi gipoksii.

A marked fall in arterial blood pressure, organ blood flow rates and tissue perfusion in the liver, kidneys and brain was registered by ultrasound and laser Doppler flowmetry in rats with low (LR) and high resistance (HR) to circulatory hypoxia (average life spans less than 1.5 h and more than 3 h were 42 and 58%, respectively) at the end of acute massive hemorrhage. In the posthemorrhagic period organ hemodynamics and microcirculation showed a tendency to further decrease in LR rats. In HR rats blood flow in hepatic, renal and common carotid arteries were restored for a while up to 115-120%, 85-90% and 60-65%, respectively, following bleeding arrest. At this new posthemorrhagic level the brain flow was actively maintained in the compensatory phase of the posthemorrhagic period due to autoregulatory changes in the carotid resistance. Such a peculiar reaction of the brain blood vessels in HR rats is considered as an adaptive response protecting the brain during massive hemorrhage under severe tissue hypoxia against autoreperfusion and reoxygenation-induced damage.

[Individual resistance of the cardiovascular system to acute hemorrhage]. / Individual'naia ustoichivost' serdechno-sosudistoi sistemy k ostroi krovopotere.

Monitoring by ultrasonic and laser Doppler flowmetry and biomicroscopy demonstrated that rats highly resistant to acute blood loss differ in principle from rats with low resistance by the life span, pattern of changes in arterial pressure, organ hemodynamics, and microcirculation. The pumping function of the heart is intact till the end of life in all highly resistant and in 65% poorly resistant rats. After arrest of massive hemorrhage, 35% poorly resistant animals develop low cardiac output syndrome. Poorly resistant rats with severe posthemorrhagic hypotension represent a risk group in need of special pathogenetic therapy.