Structural and functional units in the pial microvascular system

A study was made of the pial arterial microcircles formed upon successive branching and anastomosing of the terminal pial vessels on the brain cortex surface at different levels of the phylogenetic development of the vertebrata. It was discovered that the pial arterial microcircles progressively become more complicated in the following order: chicken, rabbit, cat, dog, monkey. The morphological signs of the microcircles undergo progressive development: 1) they are formed primarily from small pial arterial branches possessing high vasomotor activity; 2) the area of each circle becomes less and less and their amount per unit of the brain surface increases respectively; 3) the quantity of the feeding arterial branches rises despite the reduction of the circle size; 4) the number of outgoing precortical and radial arteries entering the brain cortex increases; 5) the areas of the brain cortex supplied by individual radial arteries become less and less. This ensures increasingly delicate regulation of adequate blood supply of the smallest areas of the brain cortex.     

The extrinsic blood vessels of the ovary of the sheep.

The extrinsic ovarian blood vessels were studied in 134 ewes. In view of recent evidence that uterine luteolysis may involve venoarterial transfer of prostaglandin F2alpha in the ovarian pedicle, particular attention was paid to the interrelationships between veins and arteries. The ovarian artery and utero-ovarian vein are large vessels of conventional structure and lie in close apposition. Their walls are slightly thinner on their apposing sides. The ovarian branches of the ovarian artery are very tortuous, and closely intertwined with the plexiform ovarian branches of the utero-ovarian vein. An extensive plexus of small veins surrounds the ovarian artery and its ovarian branches. Within this plexus are many thin-walled, dilated regions, interspersed with narrow, thick-walled segments. Valves are inconstantly present at sites of entry of branches of the plexus into the major veins. Small numbers of arterio-venous anastomoses are present in the distal part of the ovarian pedicle. Unless blood can flow in a veno-arterial direction through arterio-venous anastomoses or capillary beds, the structural barrier between uterine venous and ovarian arterial blood is substantial.     

Pathological and compensatory processes in the cerebral circulation during blood transfusion shock]

In experiments on dogs the intravenous injection of heterogenous blood resulted in a decrease of total arterial pressure, weakening of the brain blood flow, fall of Po2 and pH in the brain cortex. A simultaneous constriction if inner carotid arteries is depending on direct action on the vascular wall of heterogenous proteins and on a release in it of physiologically active substances, such as serotonin. Fine pial arteries were dilated by the compensatory mechanism that was not associated with a decrease of intravascular and with direct action of hypoxia or acid metabolites on vascular walls. It was proposed that the trigger mechanism of this vasodilatation is hypoxic changes of metabolism in the nervous tissue.     

Increased hand blood flow limits other skin vasodilation

1. 1. To examine whether the increased hand blood flow (BF), mainly arteriovenous anastomoses (AVA) flow, limits an increase in other skin BF during thermal load, 7 healthy male subjects were exercised for 25 min and then rested for 20 min in wrist occlusion (OCCL) and control experiments (CONT), respectively.

2. 2. In OCCL, both wrists were occluded at pressure of 250 mmHg from the 15th min of exercise.

3. 3. In CONT, the wrists were free throughout the experiment. Finger and forearm skin temperature greatly increased in CONT, but did not rise in OCCL.

4. 4. Suppressed hand BF in OCCL induced compensatory increases of skin BF and sweat rate in the chest at least.

5. 5. However, wrist occlusion induced a significant rise in esophageal temperature and a significant fall in mean arterial pressure (MAP).

6. 6. These results suggest that the rising hand BF greatly contributes to limit the increase in other skin BFs without any fall of MAP during thermal load.

Participation of the cholinergic nervous mechanism in regulating adequate blood supply to the rabbit cerebral cortex

Dilatation of the pial arteries and their active segments (sphincters of the offshots and precortical arteries) was studied in rabbits under the conditions of enhanced neuronal activity of the brain cortex, induced by application of 0.5% strychnine to its surface. The blockade of the cholinergic transmission by microapplication of atropine to vessel walls caused a significant inhibition of the dilatatory responses of the study microvessels. Reduction of functional dilatation was most demonstrable in the precortical arteries, less marked in the sphincters of the offshots and still less marked in the small pial arteries. No differences in the responses of the large pial arteries were discovered either before or after atropine microapplications. The author suggests that the cholinergic mechanism plays an important part in regulation of adequate brain blood supply and that such a regulation may be performed locally within the area of a single radial artery occupying ca. 1/5 mm2 of the brain surface in rabbits.     

Arterial blood supply to the laryngeal part of the pharynx]

The sources, anastomoses and variations of bloodsupply of the laryngeal part of the pharynx were studied in 100 corpses of different sex and age. It has been established that the fronto-lateral divisions of the laryngeal part of the pharynx are supplied with blood by pharyngeal branches of the superior and inferior paryngeal arteries. Ligation of the pharyngeal arteries during laryngectomy prior to their entering the larynx, i. e. before the divergence of the pharyngeal branches from them, as conventional, causes restriction of supply of these parts and can contribute to disjunction of the pharyngeal suture. The trunks of laryngeal arteries with their pharyngeal branches should be preserved, if possible. The posterior wall of the laryngeal part of the pharynx is divided into three zones depending on the main arterial sources (the ascending pharyngeal, superior and inferior thyroid arteries).     

A global mathematical model of the cerebral circulation in man

A mathematical model of the cerebral circulation has been formulated. It was based on non-linear equations of pulsatile fluid flow in distensible conduits and applied to a network simulating the entire cerebral vasculature, from the carotid and vertebral arteries to the sinuses and the jugular veins. The quasilinear hyperbolic system of equations was numerically solved using the two-step Lax-Wendroff scheme. The model's results were in good agreement with pressure and flow data recorded in humans during rest. The model was also applied to the study of autoregulation during arterial hypotension. A close relationship between cerebral blood flow (CBF) and capillary pressure was obtained. At arterial pressure of 80 mmHg, the vasodilation of the pial arteries was unable to maintain CBF at its control value. At the lower limit of autoregulation (60 mm Hg), CBF was maintained with a 25% increase of zero transmural pressure diameter of nearly the whole arterial network.     

Plasticity of blood vessels of the heart and lungs in collateral circulation under conditions of high altitude]

The combination of the collateral blood flow in the heart and lungs with effects of Alpine hypoxia and pronounced additional loads was found to allow the detecting of plastical capacities of these organs in a sufficiently full volume. The experiments were performed in 273 dogs by microscopic, macro-microscopic, macroscopic and partly functional methods. The collateral coronary blood flow (after ligation of the anterior interventricular artery) under Alpine conditions (3200 m over the sea level) combined with compensatory hyperfunction of the heart (due to stenosing of the aorta arc), gets worse as compared with the conditions of the valley. In these experiments in mountains the extra- and intraorganic anastomoses are more pronounced, the capacity of the coronary artery branches being less pronounced than in the valley. The muscle fibres grow thicker, the heart weight enlarges, the diffusion distances of capillaries increase and the ratio of the arterial bed capacity and the heart weight decreases. Under Alphine conditions (as compared with the valley) the collateral blood flow of lungs deteriorates (after ligation of two lobar branches of the pulmonary artery or of the lobar vein) against the background of additional loads (stenosing of the aorta arc or pulmonectomy). Deterioration of the collateral bloodflow is related with the combination of conditions of the alphine hypoxia with additional loads resulting in a weakening or even block of compensatory reactions of pulmonary or bronchial arteries and veins.     

Effect of angiotensin II and peptide YY on cerebral and circumventricular blood flow

Angiotensin II and peptide YY (PYY) are putative neuro/humoral agents acting at several circumventricular regions. These peptides also constrict cerebral vessels. We examined the effect of acute intravenous infusion of saline, angiotensin II and peptide YY on local cerebral blood flow (14C-iodoantipyrine autoradiography) in the circumventricular and non-circumventricular brain regions of 17 conscious rats. No reductions in brain blood flow (28 regions) were observed although angiotensin II and PYY infusion elevated arterial blood pressure 15-25% without influencing heart rate, suggesting an increase in peripheral resistance. However, local blood flow was dependent on the peptide infused. During PYY infusion, blood flow was rather constant in the 20 non-circumventricular regions examined whereas an increase in blood flow and a slight decrease in cerebrovascular resistance occurred in the circumventricular regions. The area postrema exhibited the most pronounced changes--an elevation in blood flow of 44 +/- 11% and a reduction in resistance of 20 +/- 5% in comparison to that in control animals. During angiotensin II infusion, local cerebral blood flow was similar to that in controls and local cerebrovascular resistance was elevated. Thus, the local cerebral circulatory response to peptide administration was dependent on the location of the region examined (circumventricular or non-circumventricular) and on the vasoactive peptide infused.     

Alteration of pial vessel responses to blood pressure changes in rats after hypoxia

Previous studies in newborn lamb have shown impairment of cerebral blood flow autoregulation after hypoxia followed by reoxygenation. The present study was done to see if such a phenomenon existed in the adult rat and if it could be demonstrated at the level of the pial arterioles. Using an open cranial window preparation, we assessed the changes in pial vessel diameter during blood pressure alterations induced by hemorrhage and reinfusion of blood, before and after 30 s of hypoxia, in 15 male Sprague-Dawley rats. Mean diameters of pial arteries in the study group of rats were 128 +/- 54 microns before hypoxia and 141 +/- 61 microns after normoxia following hypoxia. The corresponding diameters in rats serving as time controls were 136 +/- 52 and 138 +/- 52 microns. Slopes of pial vessel diameters as a function of mean arterial blood pressures decreased significantly (p less than 0.05) after hypoxia from -0.86 +/- 0.45 to 0.03 +/- 0.66 (mean +/- SD). In the control rats not subjected to hypoxia, the slopes remained unchanged over a similar time period (-0.60 +/- 0.16 and -0.42 +/- 0.19). The negative slopes indicate that pial vessels dilate during hypotension and constrict during hypertension. Such vascular responses may play a role in autoregulation of cerebral blood flow. We found that a relatively brief period of hypoxia can cause a long-lasting impairment of vascular responses even after restoration of normoxia. These findings are consistent with a previous report of persistent impairment of cerebral blood flow autoregulation after a brief period of hypoxia.     

Numerical simulation of local blood flow in the carotid and cerebral arteries under altered gravity

A computational fluid dynamics (CFD) approach was presented to model the blood flows in the carotid bifurcation and the brain arteries under altered gravity. Physical models required for CFD simulation were introduced including a model for arterial wall motion due to fluid-wall interactions, a shear thinning fluid model of blood, a vascular bed model for outflow boundary conditions, and a model for autoregulation mechanism. The three-dimensional unsteady incompressible Navier-Stokes equations coupled with these models were solved iteratively using the pseudocompressibility method and dual time stepping. Gravity source terms were added to the Navier-Stokes equations to take the effect of gravity into account. For the treatment of complex geometry, a chimera overset grid technique was adopted to obtain connectivity between arterial branches. For code validation, computed results were compared with experimental data for both steady-state and time-dependent flows. This computational approach was then applied to blood flows through a realistic carotid bifurcation and two Circle of Willis models, one using an idealized geometry and the other using an anatomical data set. A three-dimensional Circle of Willis configuration was reconstructed from subject-specific magnetic resonance images using an image segmentation method. Through the numerical simulation of blood flow in two model problems, namely, the carotid bifurcation and the brain arteries, it was observed that the altered gravity has considerable effects on arterial contraction/dilatation and consequent changes in flow conditions.     

Metoprolol impairs resistance artery function in mice

Acute β-blockade with metoprolol has been associated with increased mortality by undefined mechanisms. Since metoprolol is a relatively high affinity blocker of β(2)-adrenoreceptors, we hypothesized that some of the increased mortality associated with its use may be due to its abrogation of β(2)-adrenoreceptor-mediated vasodilation of microvessels in different vascular beds. Cardiac output (CO; pressure volume loops), mean arterial pressure (MAP), relative cerebral blood flow (rCBF; laser Doppler), and microvascular brain tissue Po(2) (G2 oxyphor) were measured in anesthetized mice before and after acute treatment with metoprolol (3 mg/kg iv). The vasodilatory dose responses to β-adrenergic agonists (isoproterenol and clenbuterol), and the myogenic response, were assessed in isolated mesenteric resistance arteries (MRAs; ～200-μm diameter) and posterior cerebral arteries (PCAs ～150-μm diameter). Data are presented as means ± SE with statistical significance applied at P < 0.05. Metoprolol treatment did not effect MAP but reduced heart rate and stroke volume, CO, rCBF, and brain microvascular Po(2), while concurrently increasing systemic vascular resistance (P < 0.05 for all). In isolated MRAs, metoprolol did not affect basal artery tone or the myogenic response, but it did cause a dose-dependent impairment of isoproterenol- and clenbuterol-induced vasodilation. In isolated PCAs, metoprolol (50 μM) impaired maximal vasodilation in response to isoproterenol. These data support the hypothesis that acute administration of metoprolol can reduce tissue oxygen delivery by impairing the vasodilatory response to β(2)-adrenergic agonists. This mechanism may contribute to the observed increase in mortality associated with acute administration of metoprolol in perioperative patients.     

Vascularization of the pituitary of the Australian lungfish and Neoceratodus forsteri

The vascularization of the brain and the pituitary region of the Australian lungfish, Neoceratodus forsteri is described from serial section reconstruction. The distal lobe has no direct arterial blood supply and receives blood solely from a pituitary portal system basically similar to that of other sarcopterygians. The primary capillary plexus of the median eminence receives its arterial blood from the infundibular arteries, which on their way distribute some small branches to the prechiasmatic region. The primary plexus also receives capillaries from the adjacent pial hypothalamic plexus. The primary capillary plexus of the median eminence comprises a rostral 'uncovered' and caudal 'covered' part which are not sharply delineated. Distinct portal vessels connect the 'uncovered' rostral part of the primary plexus with the secondary capillary plexus supplying the rostral subdivision of the pars distalis. The 'covered' caudal part of the primary plexus merges into the proximal subdivision of the pars distalis, apparently without formation of distinct portal vessels. The primary plexus has some connections with the plexus intermedius via a hypophysial stem capillary plexus. The plexus intermedius has a substantial arterial supply and gives off capillaries to the parenchyma of the pars intermedia. The adenohypophysis is drained into an unpaired hypophysial vein. The significance of the vascular pathways is discussed from comparative, functional, and evolutionary viewpoints.     

A mathematical model of twin-twin transfusion syndrome with pulsatile arterial circulations

The twin-twin transfusion syndrome (TTTS) is a severe complication of monochorionic twin pregnancies caused by a net transfusion of blood from one twin (the donor) to the other (the recipient) through placental anastomoses. To examine the pathophysiology of TTTS evolving through clinical stages I to IV, we extended our mathematical model to include pulsating circulations propagating along the arterial tree as well as placental and cerebral vascular resistances, and arterial wall thickness and stiffness. The model demonstrates that abnormal umbilical arterial flow (TTTS stage III) in the donor twin results from increased placental resistance as well as reduced resistance in the cerebral arteries. In contrast, recipient twin abnormal umbilical arterial flow requires a significantly greater increase in placental resistance, resulting from the compressive effects of high amniotic fluid pressure. Thus simulated abnormalities of donor umbilical arterial pulsations occur in the donor more commonly and earlier than in the recipient. The "normal" staging sequence (I, II, III, IV) correlates with the presence of compensating placental anastomoses, constituting the majority of monochorionic twin placentas. However, TTTS stage III may occur before manifestations of stage II (lack of donor bladder filling), in our model correlating with severe TTTS from a single arteriovenous anastomosis, an infrequent occurring placental angioarchitecture. In conclusion, this mathematical model describes the onset and development of the four stages of TTTS, reproduces a variety of clinical manifestations, and may contribute to identifying the underlying pathophysiology of the staging sequence in TTTS.     

Increased osmolality of conscious water-deprived rats supports arterial pressure and sympathetic activity via a brain action

To test the hypothesis that high osmolality acts in the brain to chronically support mean arterial pressure (MAP) and lumbar sympathetic nerve activity (LSNA), the osmolality of blood perfusing the brain was reduced in conscious water-deprived and water-replete rats by infusion of hypotonic fluid via bilateral nonoccluding intracarotid catheters. In water-deprived rats, the intracarotid hypotonic infusion, estimated to lower osmolality by approximately 2%, decreased MAP by 9+/-1 mmHg and LSNA to 86+/-7% of control; heart increased by 25+/-8 beats per minute (bpm) (all P<0.05). MAP, LSNA, and heart rate did not change when the hypotonic fluid was infused intravenously. The intracarotid hypotonic fluid infusion was also ineffective in water-replete rats. Prior treatment with a V1 vasopressin antagonist did not alter the subsequent hypotensive and tachycardic effects of intracarotid hypotonic fluid infusion in water-deprived rats. In summary, acute decreases in osmolality of the carotid blood of water-deprived, but not water-replete, rats decreases MAP and LSNA and increases heart rate. These data support the hypothesis that the elevated osmolality induced by water deprivation acts via a region perfused by the carotid arteries, presumably the brain, to tonically increase MAP and LSNA and suppress heart rate.     

Axial shift of erythrocytes in arteries supplying blood to the cerebral cortex

In experiments with rabbits the widths of the axial flows of erythrocytes and of the parietal plasma layers were assessed in pial arterial ramifications supplying the cerebral cortex after their in vivo and in situ fixation under conditions of control and vasodilatation. A strict proportional relationship was revealed between the width of red cell flows and the diameter of pial arteries of 15-200 microns wide. However, the relative plasma volume in the microvessels below 50 microns in diameter was comparatively greater than in the larger vessels. The obtained results prove the feasibility of assessing the microvessels' diameters in tissues where one can see the red cell flow but the vascular walls are invisible. One of the reasons for the lower hematocrit in smaller blood vessels as compared to the larger ones was also elucidated.     

Dynamic changes in organ blood flow and oxygen consumption during acute asphyxia in fetal sheep

The effects of acute asphyxia on both the time course of blood flow changes in central and peripheral organs, including the skin, and the time course of changes in oxygen consumption were studied in 9 unanaesthetized fetal sheep in utero at 130 +/- 2 days of gestation during 4-min arrest of uterine blood flow. Blood flow distribution and total oxygen consumption were determined at 1-min intervals during asphyxia using isotope-labelled microspheres (15 micrograms diameter) and by calculating the decline of the arterial O2 content, respectively. During asphyxia peripheral blood flow including that to the skin, scalp, and choroid plexus decreased rapidly, whereas blood flow to the heart, brain stem and (in surviving fetuses only) adrenals increased slowly. Total oxygen consumption fell exponentially with time and was closely correlated with the fall in both arterial oxygen content and peripheral blood flow; the time courses of these changes were very similar to those of the decreasing blood flows to the skin and scalp. Blood flow within the brain was redistributed at the expense of the cerebrum and the choroid plexus; the total blood flow to the brain did not change. In the 5 fetuses that died during the recovery period adrenal blood flow failed to increase and, at the nadir of asphyxia, peripheral vessels dilated and central vessels constricted. We conclude that in fetal sheep near term during acute asphyxia the time course of changes in blood flow to central and peripheral organs is different; total oxygen consumption depends on arterial O2 content and peripheral blood flow; total blood flow to the brain does not change, but is redistributed towards the brain stem at the expense of the cerebrum and choroid plexus; fetal death is preceded by a failure of adrenal blood flow to increase, by peripheral vasodilatation, and by central vasoconstriction and skin blood flow validly indicates rapid changes in the distribution of blood flow and the changes in oxygen consumption that accompany it.     

Effect of prostaglandins E2 and F2α on umbilical blood flow and fetal hemodynamics

The hemodynamic effects of PGF_2α, PGE₂, and norepinephrine injected into the umbilical arterial circulation were compared in nine fetal lambs in utero. Umbilical blood flow was measured with radioactive microspheres and an electromagnetic flow transducer implanted on the distal aorta of the fetus after ligation of external iliac arteries and other accessible distal aortic branches.PGF_2α and norepinephrine increased fetal arterial pressure and umbilical blood flow while umbilical vascular resistance increased slightly (PGF_2α) or not at all (norepinephrine). PGE₂ increased fetal arterial pressure, decreased umbilical blood flow, and exerted a profound active vasoconstrictor effect on the fetal placental bed. Our data taken together with the observations of others suggest that prostaglandins may play a role in the circulatory adaptations of the fetus at birth and that PGE₂ in high concentrations is likely to have deleterious hemodynamic consequences in the fetus in utero.     

Histochemical studies of the microvascular effectors regulating blood supply to the cerebral cortex

The innervation of the pial arteries as well as the activity of enzymes (phosphorylase I, II, III, succindehydrogenase, lactate dehydrogenase, ATPase, GTPase and CTPase) responsible for vascular smooth muscle function were studied histochemically on total microscopic preparations of rabbit pia matter. An especially rich adrenergic and cholinergic innervation was found around the active microvascular effectors - sphincters of pial and precortical arterial off-shoots. The nerve fibers followed the radial arteries entering the cerebral cortex. No differences were detected between the pial arteries and active microvascular effectors in the enzyme activity.     

Middle cerebral artery flow velocity and blood flow during exercise and muscle ischemia in humans.

Changes in middle cerebral artery flow velocity (Vmean), measured by transcranial Doppler ultrasound, were used to determine whether increases in mean arterial pressure (MAP) or brain activation enhance cerebral perfusion during exercise. We also evaluated the role of "central command," mechanoreceptors, and/or muscle "metaboreceptors" on cerebral perfusion. Ten healthy subjects performed two levels of dynamic exercise corresponding to a heart rate of 110 (range 89-134) and 148 (129-170) beats/min, respectively, and exhaustive one-legged static knee extension. Measurements were continued during 2-2.5 min of muscle ischemia. MAP increased similarly during static [114 (102-133) mmHg] and heavy dynamic exercise [121 (104-136) mmHg] and increased during muscle ischemia after dynamic exercise. During heavy dynamic exercise, Vmean increased 24% (10-47%; P less than 0.01) over approximately 3 min despite constant arterial carbon dioxide tension. In contrast, static exercise with a higher rate of perceived exertion [18 (13-20) vs. 15 (12-18) units; P less than 0.01] was associated with no significant change in Vmean. Muscle ischemia after exercise was not associated with an elevation in Vmean, and it did not provoke an increase in Vmean after static exercise. Changes in Vmean during exercise were similar to those recorded with the initial slope index of the 133Xe clearance method. The data show that middle cerebral artery mean flow velocity reflects changes in cerebral perfusion during exercise. Furthermore, they support the hypothesis that cerebral perfusion during exercise reflects an increase in brain activation that is independent of MAP, central command, and muscle metaboreceptors but is likely to depend on influence of mechanoreceptors.