Search

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 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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.