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.

[Particularities of adrenergic regulation and the function of cardiovascular system at remote periods after myocardial infarction in rats of different strains].

UNLABELLED: Heart function was studied in the August rats with innate raised sympathetic-adrenal system and in the Wistar rats through the period of 3 month after myocardial infarction. The sizes of the postinfarction scars were similar in the rats under comparison (56-62%) but end-diastolic pressure in Wistar rats and in August rats was 18.7 +/- 2.2 mm Hg and 11.8 +/- 0.7 mm Hg. Under the maximum isometric load induced by the aorta coarctation, the work efficiency of the heart in the August rats was greater than in the Wistar rats. During the postinfarction period, plasma catecholamine (CA) in August rats was higher than in Wistar rats. In the adrenal glands, the CA contents in August rats increased and in Wistar rats decreased. The activity of CA resynthes in the adrenal glands and in the hypothalamus in August rats did not change and in Wistar rats increased. The blood contents of nitrate and nitrite and hemine oxygenase-1 level in the myocardium of August rats were increased in contrast to Wistar rats. THE CONCLUSION: the higher viability of the myocardium in August rats with long existing postinfarction cardiasclerosis is to a considerable extent associated with lowered activation of the sympathetic-adrenal system under more expressing activation of NO-system and antioxidant protection.

Effect of picrotoxin on organism's resistance to acute severe hypoxia.

Organism's resistance to acute severe hypoxia (3% O2) was studied after administration of GABA(A) receptor antagonist picrotoxin and adenosine receptor antagonist euphylline (aminophylline) and after neutralization of secondary hypocapnia by adding 7% CO2 to the hypoxic mixture. Administration of picrotoxin to anesthetized rats increased animal resistance to hypoxia. The resistance to hypoxia decreased after treatment with euphylline. Neutralization of secondary hypocapnia by adding 7% CO2 to the hypoxic mixture had no effect on animal lifespan.

Effect of lithium hydroxybutyrate on hemodynamics and respiration in rats with different resistance to hypoxia.

Acute experiments on narcotized rats showed that intravenous infusion of GABA derivative lithium hydroxybutyrate induced different changes in hemodynamic and respiratory parameters in animals with high and low resistance to hypoxia. Rats highly resistant to hypoxia better tolerated lithium hydroxybutyrate treatment compared to low resistant animals.

Effect of pyrrolidone-pyroglutamic acid composition on blood flow in rat middle cerebral artery.

We compared the effects of a pyrrolidone-pyroglutamic acid composition and nimodipine on blood circulation in the middle cerebral artery in rats. The composition produced a strong effect on blood supply to the brain, stimulated blood flow in the middle cerebral artery (by 60 +/- 9%) and decreased blood pressure (by 25.0 +/- 2.7%). The cerebrovascular effects of this composition differed from those of nimodipine. Nimodipine not only increased middle cerebral artery blood flow, but also decreased cerebral blood flow in the early period after treatment.

Selective blockade of central m1 muscarinic cholinergic receptors with pirenzepine impairs cardiovascular and respiratory function in rats with acute hemorrhage.

Ultrasound studies showed that selective antagonist of central M1 muscarinic cholinergic receptors pirenzepine (50 mg/kg intravenously) causes transitory hypotension and respiratory depression in anesthetized intact rats. The M1 receptor antagonist had no effect on cardiac output and portal blood flow. Pretreatment with pirenzepine increased the sensitivity of rats with acute massive hemorrhage to circulatory hypoxia. After blockade of central M1 muscarinic cholinergic receptors, the posthemorrhagic period was characterized by primary decompensation of blood pressure, portal blood flow, and respiration and development of low cardiac output syndrome. The animals died over the first minutes after bleeding arrest. Our results indicate that central M1 muscarinic cholinergic receptors act as shock-limiting cholinergic structures under conditions of posthemorrhagic changes in systemic and portal blood flow, as well as during respiratory dysfunction.

Role of cholinergic structures in individual resistance of rat circulatory system to posthemorrhagic hypoxia.

Experiments employing ultrasound technique showed that nonselective blockade of central muscarinic cholinoceptors with amizyl significantly increases the number and lifespan of rats highly resistant to acute massive blood loss. This pretreatment increased individual resistance of the circulatory system to posthemorrhagic hypoxia (blood pressure and portal blood flow rate). Preliminary blockade of central nicotinic cholinoceptors and peripheral muscarinic cholinoceptors with cyclodol and methacin, respectively, had no effect on the percentage of rats highly and low resistant to acute blood loss. Preliminary blockade of peripheral muscarinic cholinoceptors with methacin prevented the decrease in the cardiac output in low resistant animals during the posthemorrhagic period.

Changes in hemodynamics and respiration in rats with different resistance to acute hypoxia.

Effects of acute hypoxia on hemodynamics and respiration were studied in acute experiments on narcotized rats. The animals were divided into groups characterized by high, low-, and medium- resistance to hypoxia by the time of respiration arrest during inhalation of gas mixture containing 3% O2. Hemodynamic parameters of highly resistant animals were higher than in low-resistant rats throughout the entire hypoxic period. The development of a rare (with prolonged inspiratory phase) respiratory rhythm in highly resistant rats is an adaptive reaction, which allows them longer tolerate hypoxia compared to low-resistant animals.

Blood flow measurements in studies of macro- and microcirculation.

Ultrasound blood flow transducers were tested by using pulsating flows in a dynamic test system with Pito tube. Simultaneous studies of rat ascending aorta with a Doppler strip detector (13 MHz) and ultrasound catheter (33 MHz) produced a 10% discrepancy of the results. Here we describe a computing unit to estimate the volume flow rate in biomicroscopic studies. The value of blood flow rate estimated with a 38.5-MHz Doppler probe and diameter of the microscopically examined vessel were inputted into a computer for real-time processing. Blood flow rate in microvessels of rat mesentery and cremaster muscle was 10-700 nl/sec.

Ultrasound as a tool in experimental research of macro- and microcirculation.

Peculiarities of application of two modes of ultrasonic measurements of blood flow in experimental research are considered, which are based on Doppler effect and on differential transit-time of upstream and downstream sound propagation. The efficiency of high-frequency ultrasound flowmeter equipped with 26.8 MHz transducers was demonstrated in measurements of blood flow in rat midbrain and coronary arteries. This approach can be used for evaluation of the dynamics of cardiac output with an intravascular catheter 0.6 mm in diameter working at 33 MHz. The probe and electronic scheme of the devise for measuring blood flow in microvessels are described. Blood flow rate measured in mesentery and m. cremaster arterioles under normal conditions was 2-12 mm/sec. One-element probe working at 38.5 MHz provided stable recording of blood microflows in 30-40-micro vessels.

[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.

Effect of gaseous media on the balance between cardiac outputs of the right and left ventricles.

Acute experiments on cats showed that mild hypoxia did not disturb the balance between right and left ventricular outputs. Breaching 3% O(2) shifted this balance by reducing right ventricular output in cats with low resistance to hypoxia. Spontaneous breathing hypercapnic gas mixtures shifted this balance towards the left ventricular output. During artificial ventilation under open chest conditions, hypercapnia induced opposite changes and shifted the balance towards the right ventricular output.

[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.