Influence of gravitational overload and hypokinesia on the structure of the vascular bed of the stomach]

Under study were effects of gravitation stresses, total hypokinesia and their combinations on blood vessels of the stomach. The work was carried out in 130 rabbits, 16 of them being used to study the normal structure of the gastric vascular bed. The vascular bed was injected with the Gerota's mass followed by clearing, making histological preparations and roentgenography. The investigation has revealed both quantitative and qualitative changes in the structure of the gastric blood vessels. The maximum endurable stress of the ventro-dorsal direction causes morphological shifts less pronounced than stresses of longitudinal directions. With prolonged terms of hypokinesia (1-12 weeks) morphological changes became more pronounced in all the layers of the stomach. A combination of successive gravitation stresses and hypokinesia during 4-12 weeks aggravated morphological changes which occurred after exposure to isolated above factors. The animals subjected to maximum endurable stresses before and after 4-week hypokinesia developed vascular changes more typical for the effects of gravitation. The pretraining of animals did not give a pronounced positive effect on the changes of the angioarchitectonics of all the gastric layers after a repeated stress following 4-week hypokinesia.     

The effect of catecholamines on blood circulation in the liver

In acute experiments on dogs under nembutal anaesthesia the pressure and blood flow in the vessels supplying the liver have been recorded simultaneously with registration of the hepatic blood content changes. Catecholamines injected into liver vessels have been found to change significantly the liver circulation: adrenaline and noradrenaline evoke the constriction of intrahepatic vessels and decrease the blood content in the liver, realising through the alpha-adrenoreceptors activation, isadrin causes a weak vasodilatation by the activation of beta-adrenoreceptors. A selective inactivation of isadrin in the liver is shown. The density of alpha-adrenoreceptors distribution in the intrahepatic vessels is large enough and apparently some times exceeds the density of beta-adrenoreceptors. In 1/3 of dogs the beta-adrenoreceptors in the liver vascular bed are absent at all or present in arterial bed only.     

Study of the microcirculation of the wall of the stomach of white rats by the vital microscopy method]

Microcirculation of the gastric wall in the albino rat was studied by the method of vital microscopy in passing light. The conditions of the experiment permitted watching the microcirculation state during 5-6 hours. Intravital morphometry of the microcirculation bed vessels was made. The obtained data concerning the intravital angioarchitectonics of the gastric wall vascular bed were in good agreement with a conventional scheme of its blood supply. The role of arteriolevenular anastomoses in redistribution of blood within the bloodflow pathways was noted.     

The neurogenic constrictor response of isolated rat saphenous artery is reduced after 2-week tail suspension

Under real or simulated microgravity conditions the control of arterial vascular tone is greatly disturbed. The low arterial vessel reactivity to sympathetic influences may be the cause of an increase in flow in hind limb skeletal muscles in tail-suspended (TS) rats. Our previous experiments with constant pressure perfusion of rat hind limb demonstrated the reduced vasoconstrictor responses to sympathetic nerve stimulation in TS rats. Responses to exogenous noradrenaline depended on the perfusion conditions. It is known that the vessels of various branching orders noticeably differ in nerve density and in sensitivity to vasoconstrictor agonists. So under neurogenic or exogenous noradrenaline influences the vascular resistance may be increased at different levels of vascular bed, thus making the data analysis seriously complicated. This uncertainty may be overcome by investigation of a single vessel isolated from hind limb vascular bed. The saphenous artery, a resistance artery with dense innervation, is a very convenient object for this purpose. Thus, this study was aimed at comparing the effects of 2-week tail suspension upon the constrictor responses of isolated saphenous artery to neurogenic and exogenous noradrenaline stimuli in rats.     

Raised tone reveals ATP as a sympathetic neurotransmitter in the porcine mesenteric arterial bed

The relative importance of ATP as a functional sympathetic neurotransmitter in blood vessels has been shown to be increased when the level of preexisting vascular tone or pressure is increased, in studies carried out in rat mesenteric arteries. The aim of the present study was to determine whether tone influences the involvement of ATP as a sympathetic cotransmitter with noradrenaline in another species. We used the porcine perfused mesenteric arterial bed and porcine mesenteric large, medium and small arteries mounted for isometric tension recording, because purinergic cotransmission can vary depending on the size of the blood vessel. In the perfused mesenteric bed at basal tone, sympathetic neurogenic vasocontractile responses were abolished by prazosin, an α₁-adrenoceptor antagonist, but there was no significant effect of α,β-methylene ATP, a P2X receptor-desensitizing agent. Submaximal precontraction of the mesenteric arterial bed with U46619, a thromboxane A₂ mimetic, augmented the sympathetic neurogenic vasocontractile responses; under these conditions, both α,β-methylene ATP and prazosin attenuated the neurogenic responses. In the mesenteric large, medium and small arteries, prazosin attenuated the sympathetic neurogenic contractile responses under conditions of both basal and U46619-raised tone. α,β-Methylene ATP was effective in all of these arteries only under conditions of U46619-induced tone, causing a similar inhibition in all arteries, but had no significant effect on sympathetic neurogenic contractions at basal tone. These data show that ATP is a cotransmitter with noradrenaline in porcine mesenteric arteries; the purinergic component was revealed under conditions of partial precontraction, which is more relevant to physiological conditions.     

Condition of the microcirculatory bed of the bulbar conjunctiva in physiological and pathological pregnancies

By means of biomicroscopic method the bulbar conjunctiva in 150 women (18-35 years of age) have been examined. Of them: 30 healthy women make the control group; the second group includes 60 healthy women at their first and second half of pregnancy; the third group includes 60 women with pregnancy developing against the background of noncomplicated insulin-dependent diabetus mellitus during their first and second half of pregnancy. In the healthy women there are not any significant changes in most of the parameters of the microcirculatory bed during the first half of their pregnancy, and in the second half of their pregnancy a great density of the blood vascular bed is determined. Diameters of all vessels in the hemomicrocirculatory bed are significantly increased, as compared to those in the control group. In the women suffering from diabetus mellitus, during the first half of pregnancy certain changes in the picture of the vascular network is observed, as well as an increased convolution. uneveness in distribution of blood vessels; in the second half of their pregnancy a pronounced deformity of the vacular network is observed, decreasing diameter of afferent vessels and an essential dilatation of postcapillaries and venules are registered. Certain signs of aggregation of blood formed elements is noted.     

Effect of general hypokinesia on the blood vessels of the medulla oblongata, pons and midbrain of the rabbit]

The work was performed on 40 rabbits. After injection of the blood system with Gerota's mass 120 mu horizontal sections were cleared after A. M. Malygin and stained with hematoxylin and eosin after Van Gieson. It was shown that within 1--3 weeks of staying in small cages the animals had dilated vein all areas of the brain under investigation. Within 4-12 weeks there appeared deformity, sharp sinuosity, disorders in usual orientation of vessels. Within 13-16 weeks of hypokinesia both qualitative and quantitative changes in blood vessels became more pronounced. It was also shown that readaptation for 1--3 weeks after 4--13 weeks of hypokinesia failed to repair the normal structure of blood vessels of the brain and that in all the parts under study the reactions of the circulatory bed structure to hypokinesia were of the same type.     

Influence of alpha and beta adrenergic receptors blockade on the adrenolytic effect of muscular work

The changes in the response of adrenergic receptors alpha and beta in the blood vessels in the working muscles in a hindlimb in cats were studied after intra-arterial administration of noradrenaline, isoprenaline and during electric stimulation of the sympathetic trunk. The experiments were carried out during alpha-adrenergic receptors blockade with dihydroergotamine (0.3 mg/kg) beta-adrenergic receptors blockade with propranolol (1 mg/kg) and blockade of acetylcholine M receptors with atropine (0.5 mg/kg). The investigations were performed at rest, during exercise (electric stimulation of the sciatic nerve) and after the exercise. The following results deserve attention: 1) beta-adrenergic receptors blockade reduced significantly the alpha-adrenolytic effect of exercise restoring the ability of blood vessel to constriction in response to noradrenaline; 2) the vasodilator effect of isoprenaline evident in resting state and maintained to some extent during exercise was abolished completely by preceding alpha-adrenergic blockade. The changes in the reactivity of resistance vessels in working skeletal muscles to noradrenaline, with abolition of its vasoconstrictor effect, have been shown by Rein [7] and others authors [2, 5]. Similarly, it is well known that the resistance vessels contain two types of adrenergic receptors alpha and beta, and that the response of the vessels to stimulation of these receptors are different [1]. In view of the recently published observations of Jarhult and Lundvall suggesting that the beta-adrenergic receptors play an important physiological role [6] in the arterial part of the microcirculation [6] and in view of the hypothesis put forward by Kunos and Szentivanyj that alpha and beta receptors can be transformed depending on the intensity of tissue metabolism [8] it seemed worth while to study more systematically the changes of the reactivity of alpha and beta adrenergic receptors in the vascular bed of the skeletal muscles during and after muscle exercise.     

Differential effects of prostaglandins A1 and A2 on pulmonary vascular resistance in the dog.

The effects of PGA1 and PGA2 were studied in the canine pulmonary vascular bed. Infusion of PGA1 into the lobar artery decreased lobar arterial and venous pressure but did not change left atrial pressure. In contrast, PGA2 infusion increased lobar arterial and venous pressure and the effects of this substance were similar in experiments in which the lung was perfused with dextran or with blood. These data indicate that under conditions of controlled blood flow PGA1 decreases pulmonary vascular resistance by dilating intrapulmonary veins and to a lesser extent vessels upstream to the small veins, presumably small arteries. The present data show that PGA2 increases pulmonary vascular resistance by constricting intrapulmonary veins and upstream vessels. The predominant effect of PGA2 was on upstream vessels and the pressor effect was not due to interaction with formed elements in the blood or platelet aggregation.     

Vasodilator action of guinea pig vasoactive intestinal polypeptide (VIP): comparison with common mammalian VIP.

The vascular activity of guinea pig (gp) and common mammalian (p) VIP were compared in anesthetized guinea pigs and dogs. In the guinea pig, intravenous injections of gpVIP and pVIP increased pancreatic blood flow and reduced the systemic arterial pressure and pancreatic vascular resistance in a dose-related manner. There were no significant differences in the vasodilator actions of these two VIPs, indicating that the overall cardiovascular actions of gpVIP and pVIP are similar in guinea pigs. In the dog, gpVIP, when given intra-arterially, was less potent (about 1/4) than pVIP in its action on femoral blood flow, suggesting that the blood vessels of the dog hind leg are more sensitive to its own VIP than to gpVIP. Oxidation of pVIP and gpVIP with H2O2 greatly reduced their vasodilator effects on the femoral arterial blood flow. The vascular effects were restored to control levels by reduction of the oxidized peptides with mercaptoethanol, which suggests that methionine residues of gpVIP and pVIP are important in the vasodilator effect on the femoral arterial bed in dogs.     

Response of muscular and cutaneous vessels to physiologic stimulation of chemoreceptors (38505).

Experiments were performed to determine whether physiologic stimulation of carotid chemoreceptors produces different responses in blood vessels of skin and muscle. Carotid chemoreceptors of anesthetized dogs were stimulated with hypoxic and hypercapnic blood and responses were observed in the isolated, perfused gracilis muscle and hindpaw. Chemoreceptor stimulation produced vasoconstriction in the muscle and vadodilatation in the paw (a predominantly cutaneous vascular bed). Responses to hypoxia without hypercapnic acidosis tended to be less pronounced. The study indicates that physiologic stimulation of carotid chemoreceptors produces contrasting responses in different vascular beds.     

Treatment of hypertension with ketanserin,a new selective 5-HT2 receptor antagonist.

The new selective 5-HT2 receptor blocking agent ketanserin was given in a dose of 10 mg intravenously to 12 patients with essential hypertension. It caused a distinct fall in supine systemic arterial, right atrial, pulmonary artery, and pulmonary capillary "wedge" pressures. Cardiac output, renal blood flow, and glomerular filtration rate showed no persistent changes. Thus 5-HT2 receptor blockade caused dilatation of both resistance and capacitance vessels and of the renal vascular bed. Heart rate and plasma concentrations of renin and noradrenaline rose after ketanserin. These data suggest that 5-HT may have a role in maintaining high blood pressure.     

Microcirculatory disorders in the connective tissue structures of certain organs in traumatic shock with acute hemorrhage]

The present work is a fragment of the author's complex study of replantation of an extremity in experiment. Experiments on reproduction of the model of traumatic shock with acute loss of blood under conditions of muscle relaxation proposed by Yu. V. Kiprenski were performed in 15 dogs and 10 cats. It was established that in animals dead as a result of shock there appeared severe disorders of microcirculation in tissues and organs. They were characterized by a pronounced spasm of the vessels of the arteriolar link and dilatation of the venular and lymph collectors of the microcirculation bed. Simultaneously a great number of arterio-venular anastomoses were opened through which the arterial blood was shunted partly to avoid constricted capillaries. In the vessels of the venular link of the microcirculatory bed there appeared aggregations of formed elements of blood and microemboles. In absence of specific complex therapy, as it was in our experiments, the animals die of shock within the period from 17 min to 5 hour 20 min.     

Physiological assessment of the method of autohemoperfusion through activated carbon

The results of study of the sorption properties of phenolformaldehide-activated coal in respect of several physiologically active substances from the physiological saline under static conditoins and under conditions of autohemoperfusion of the limb vessels in experimental animals are presented. Phenolformaldehide-activated coal proved to sorb actively serotonin, adrenaline and noradrenaline, and--to a lesser extent--histamine from physiological saline. Serotonin, adrenaline, noradrenaline, and acetylcholine are sorbed well, histamine--less, papaverine--very weakly from the flowing blood. No alteration of the systemic arterial blood pressure was noted with the inclusion of phenolformaldehide-activated coal into the animal's arterial circulation; a fall of perfusion pressure associated with the decreased vascular resistance occured in a number of cases.     

Endothelin produces pulmonary vasoconstriction and systemic vasodilation

Endothelin is a newly described polypeptide derived from endothelial cells. The effects of porcine endothelin on the pulmonary vascular bed and systemic vascular bed were investigated in the anesthetized, intact-chest cat under conditions of constant pulmonary blood flow and left atrial pressure. Intralobar bolus injections of porcine endothelin (100-1000 ng) produced a mild vasoconstrictor response in the pulmonary vascular bed. The pulmonary vasoconstrictor response to endothelin was not altered when pulmonary vasomotor tone was increased by infusion of U46619. In contrast to this mild pulmonary vasoconstrictor response, endothelin decreased systemic arterial pressure. Moreover, injections of porcine endothelin into the right and left atria produced similar reductions in aortic pressure as well as similar increases in cardiac output and decreases in systemic vascular resistance. The systemic vasodilator response to porcine endothelin was not affected by beta 2-adrenoceptor blockade. The present data suggest that endothelin does not undergo significant first-pass pulmonary metabolism. The pulmonary vasoconstrictor response to bolus injections of porcine endothelin is not altered by changes in pulmonary vasomotor tone. In contrast, endothelin markedly dilated the systemic vascular bed independently of activation of beta 2-adrenoceptors. The present study provides the first report of the activity of endothelin on pulmonary and systemic hemodynamics in vivo. Moreover, the potent vasodilator activity of endothelin in the systemic vascular bed and its weak effect on pulmonary vessels suggest that endothelin may be more important in the regulation of peripheral vasomotor tone than the pulmonary vascular bed.     

Regional and Species Heterogeneity of Vascular Responses: Cholinergic Muscarinic Regulation of Motor Function of Blood Vessels of Rat and Frog

Cholinergic muscarinic regulation of the motor function in several large blood vessels receiving adrenergic innervation of various degree of density was studied in the rat and the brown frog. The presence of the cholinergic component in the vascular nerve plexus and of muscarinic cholinoreceptors (M-ChR) in the vascular wall was studied by recording isometric contractions of isolated vessels in response to electric stimulation of nerves and to action of an agonist of M-ChR, 5-methylfurmetide, cholinomimetic ACh, and muscarinic cholinoblocker atropine. Cholinergic vasoconstrictory nerves were found in the vascular plexus of the rat portal vein and frog pulmonary artery, whereas M-ChR, in all vessels studied, whether they receive or do not receive the cholinergic vasoconstrictory innervation. The role of cholinergic nerves and the initial functional state of the vessels in the vascular reaction to stimulation of M-ChR as well as the regional heterogeneity of vascular responses and species heterogeneity of muscarinic cholinergic control associated with animal behavior and its habitat were demonstrated. The data obtained confirm the absence of uniformity in the structural and functional organization of blood vessels and, thereby, indicate differentiation of the mechanisms of vasomotor regulation in different zones of vascular bed in different species of vertebrate animals.     

Intraorganic venous bed of the stomach cardia in children during the first 3 years of life

The intraorganic venous bed of the gastric cardial part has been studied in 27 organs, obtained from children corpses of both sex beginning from birth up to three years of life. They died from causes that were not connected with gastric or vascular system pathology. The results of the investigation prove the presence of mucous, submucous, muscular and serous-subserous venous plexuses in the wall of the gastric cardial part in children of the first three years of life. Every membrane of the stomach wall has its specific structure of the venous link in the microcirculatory bed. In the stomach mucous membrane already in a newborn there are complexly built microcirculatory pathways. Age changes are mostly expressed in the venous link of the gastric mucous membrane; this is probably connected with functional activity of the given layer of the organ. The largest venous vessels are situated in the gastric submucous base. By the end of the newborn period and, especially fully, during the successive age periods immune protection of the gastric wall is formed as an accumulation of lymphoid tissue to an antigenic effect of food. In these age groups certain structural mechanisms of blood outflow from the gastric wall appear.     

Differential Mechanisms Associated with Vascular Disrupting Action of Electrochemotherapy: Intravital Microscopy on the Level of Single Normal and Tumor Blood Vessels

Electropermeabilization/electroporation (EP) provides a tool for the introduction of molecules into cells and tissues. In electrochemotherapy (ECT), cytotoxic drugs are introduced into cells in tumors, and nucleic acids are introduced into cells in gene electrotransfer. The normal and tumor tissue blood flow modifying effects of EP and the vascular disrupting effect of ECT in tumors have already been determined. However, differential effects between normal vs. tumor vessels, to ensure safety in the clinical application of ECT, have not been determined yet. Therefore, the aim of our study was to determine the effects of EP and ECT with bleomycin on the HT-29 human colon carcinoma tumor model and its surrounding blood vessels. The response of blood vessels to EP and ECT was monitored in real time, directly at the single blood vessel level, by in vivo optical imaging in a dorsal window chamber in SCID mice with 70 kDa fluorescently labeled dextrans. The response of tumor blood vessels to EP and ECT started to differ within the first hour. Both therapies induced a vascular lock, decreased functional vascular density (FVD) and increased the diameter of functional blood vessels within the tumor. The effects were more pronounced for ECT, which destroyed the tumor blood vessels within 24 h. Although the vasculature surrounding the tumor was affected by EP and ECT, it remained functional. The study confirms the current model of tumor blood flow modifying effects of EP and provides conclusive evidence that ECT is a vascular disrupting therapy with a specific effect on the tumor blood vessels.     

Microvasculature of the feline stomach

The feline gastric microvasculature was studied by corrosion of the injected vascular bed, which allowed evaluation of the vascular pattern of the different tunics. The serosal pattern consisted of numerous interconnected capillary vessels, forming a delicate network. Submucosal arteries supplied the muscular tunic through numerous anastomosing vessels that followed the direction of the smooth muscle fibers. The entire mucosal tunic was supplied by arterioles derived from the submucosal plexus; these gave rise to capillaries that surrounded the gastric glands and terminated in a diffuse, anastomosing subepithelial capillary network. Venules coursed through the mucosa in a perpendicular manner, forming submucosal veins.     

Effect of transverse gravitational loads on the vessels of the retinal membrane of the rabbit eyeball]

Changes in the eye ball retina were studied in 3 series of experiments in cleared preparations after exposure of the animal to gravitation stress of transversal direction. Prolonged single functionally endurable stress of ventro-dorsal direction (10 units/3 min) caused dilatation of the retina vessels, worse filling of peripheral parts of the circulatory bed, uneven staining of the vascular wall, constriction and dilatation along the course of the vessel. More continuous exposure to the same value of stresses (10 units up to the animal's death) resulted in a pressor effect; qualitative changes in the vessels increased. Within 1,5 hour after a 3-minute-long exposure to stress the vascular bed still remained unchanged. The diameter of vessels approached normal while the general quantity of vessels was decreased and qualitative changes were well pronounced.