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Numerical simulation of mass transfer in porous media of blood vessel walls.

The tunica media of a blood vessel wall is modeled as a heterogeneous medium composed of a periodic array of cylindrical smooth muscle cells and a continuous interstitial fluid phase of proteoglycan and collagen fibers. By applying Brinkman's model to describe the behavior of the interstitial flow, we obtain an analytical solution for the transmural flow field through the periodic array of smooth muscle cells in the form of a power series, making it possible to compute the convection of solutes in the interstitial phase. With reaction of solutes at the surface of smooth muscle cell membranes being treated as boundary conditions and the diffusion of species being limited to the interstitial fluid phase only, mass transfer in the media of blood vessel walls is simulated numerically using Cray supercomputers. It is found that the Sherwood number (the dimensionless mass-transfer coefficient) is not only constant for all interior smooth muscle cells but also minimally sensitive to changes of parameters controlling the relative rates of diffusion and convection in the interstitial fluid phase and the reaction on the smooth muscle cell surface. In addition, the Sherwood number is not very sensitive to changes in the volume fraction of smooth muscle cells. A homogeneous, one-dimensional model (effective-medium model) is also developed to predict the bulk concentration profile in the media, based on the equivalent properties of the effective medium derived from the heterogeneous medium. A comparison of results from the one-dimensional model and two-dimensional simulation is quite satisfactory for all practical ranges of parameters. It is also determined that, for a small molecule such as ATP, the mass transfer to the surface of smooth muscle cells is "reaction limited" as assumed previously in the literature, whereas, for a large molecule such as low-density lipoprotein, the mass transfer might not be reaction limited.

Animals↗

Distinct choline acetyltransferase (ChAT) and vasoactive intestinal polypeptide (VIP) bipolar neurons project to local blood vessels in the rat cerebral cortex.

Innervation of rat intracortical cerebral blood vessels by acetylcholine (ACh) and vasoactive intestinal polypeptide (VIP) remains largely unexplored and it is not known if the cells of origin are intra- or extracortical nor if perivascular fibers colocalize ACh and VIP. Cortical cholinergic innervation arises primarily from the basal forebrain and to a small extent from intrinsic bipolar ACh neurons thought to be the sole source of cortical VIP. In order to evaluate if intracortical perivascular ACh terminals could be distinguished from those of the basal forebrain by their colocalization with VIP, we performed a double immunofluorescence study and determined the percentage of colocalization of choline acetyltransferase (ChAT) and VIP in cortical neurons, as well as in terminal fields associated with intracortical blood vessels. From a total of 2103 cells examined in all cortical areas, VIP neurons accounted for the largest population (58.3%) followed by ChAT-positive cells (28.2%) with only 13.5% of cells being double-labelled for VIP and ChAT. Of the cortical ChAT-immunostained cells (n = 878), 32.3% colocalized VIP whereas only 18.8% of VIP neurons (n = 1509) also contained ChAT. In various cortical areas, ChAT cell bodies were seen to be contacted by VIP terminals which surrounded closely their cell soma and proximal dendrites. Perivascular fibers studied by double immunofluorescence and confocal microscopy were of three categories including cholinergic, VIPergic with a smaller population of fibers which costained for both ChAT and VIP. These results show that cortical VIP neurons are much more numerous than those containing ChAT, and that a majority of VIP neurons do not colocalize with ChAT. This observation indicates that ACh and VIP are primarily located in distinct neuronal populations and that VIP cannot be used as a marker of intracortical ACh neurons and terminals. Our results further suggest that intracortical blood vessels are primarily under the influence of distinct ChAT and VIP perivascular fibers. Also, the presence of a subset of VIP and ChAT/VIP fibers in association with intracortical blood vessels strongly suggests a role for cortical bipolar neurons in local cerebrovascular regulation. The origin of the perivascular ChAT fibers which do not colocalize VIP, however, remains unknown.

Animals↗

Two distinct types of blood vessels in clear cell renal cell carcinoma have contrasting prognostic implications.

PURPOSE: Intratumoral microvascular density (MVD) has been controversial as an indicator of prognosis in clear cell renal cell carcinoma (CCRCC). Classification of the intratumoral blood vessels based on differential expressions of blood vessel markers has not been correlated with patient prognosis in CCRCC. In this study, we aimed to evaluate the association of different categories of blood vessels with the patients' outcomes. EXPERIMENTAL DESIGN: Seventy-eight CCRCC patients who underwent nephrectomy alone were enrolled. Paraffin-embedded CCRCC tissues, together with 16 nonmalignant kidney cortex tissues, were used in tissue microarray analyses and conventional section analyses. The characteristics of intratumoral blood vessels were identified by multiple blood vessel markers and pericyte markers. A computerized image analysis program was used to quantitatively calculate the vascular density. RESULTS: Two distinct types of microvessels were identified in CCRCC: undifferentiated (CD31(+)/CD34(-)) and differentiated (CD34(+)) vessels. A higher undifferentiated MVD significantly correlated with higher tumor grades and shorter patient survival. In contrast, a higher differentiated MVD significantly correlated with lower tumor grade and longer survival. Multivariate analyses showed that undifferentiated MVD was an independent prognostic factor for patient survival. An inverse correlation between undifferentiated MVD and differentiated MVD was also identified in CCRCC. CONCLUSIONS: This is the first report showing distinct types of vasculature in CCRCC correlated with contrasting prognoses. A refined classification of CCRCC based on vasculature is therefore important for evaluating prognosis, and it may also have therapeutic implications.

Aged↗

Remodeling of the constitutive equation while a blood vessel remodels itself under stress.

Changes in the mechanical properties of a blood vessel when it remodels itself under stress are reviewed. One of the recent findings about blood vessels is the rapidity of tissue remodeling when the blood pressure is changed. When the tissue structure and material composition remodel, the zero-stress state of the vessel changes. The mechanical properties change also in the remodeling process. If the elastic behavior is expressed in terms of a pseudo-elastic strain-energy function, then the constants in the function will change in the course of the remodeling. With all these changes taking place, the scope of constitutive equations broadens: it should now include a mass-and-structure growth-stress relationship as well as a stress-strain-relationship. To obtain the mass-and-structure growth-stress relationship, one must be able to determine the mechanical properties of the different layers of the vessel wall, as well as the chemical composition and morphology. For the blood vessels, new methods of mechanical testing must be introduced. A key thought is to use bending of the blood vessel wall. By bending, different layers of the vessel wall are subjected to different stresses, leading to equations that can be used to solve the inverse problem of determining the stress-strain law from measured stress and strain. In vitro and in vivo experiments and theoretical prospectives are presented.

Adaptation, Physiological↗

Intraventricular blood vessels associated with the deep pineal gland of the Mongolian gerbil, Meriones unguiculatus.

Intraventricular blood vessels and choroidal-like cells were studied using scanning electron microscopy and correlative light microscopy. The intraventricular blood vessels were covered on their ependymal surface with a layer of cells essentially identical to the ependyma of the choroid plexus in the gerbil. Similar choroidal-like cells were seen either singly or in clusters associated with the cerebrospinal fluid-contacting pinealocytes of the suprapineal recess. Processes of the cerebrospinal fluid-contacting pinealocytes were seen extending to and making contact with the choroidal-like cells. The intraventricular blood vessels appeared to be derived from the choroid plexus, and typically took one of three courses in and around the surface of the deep pineal: (1) the vessels or their equivalent were located in the suprapineal recess with no indication of penetration into the substance of the deep pineal; (2) the vessels coursed from the suprapineal recess around the anterior surface of the habenular commissure to enter the ventral surface of the deep pineal; or (3) the vessels entered the parenchyma of the deep pineal from its dorsal surface and could be seen coursing through the substance of the gland. The close association between the choroidal-like cells and the intraventricular blood vessels with the deep pineal gland add morphological support for the possibility of interaction between the cerebrospinal fluid, or perhaps the choroid plexus, and the deep pineal gland.

Animals↗

Overproduction of nitric oxide in pathophysiology of blood vessels.

Sustained production of large amounts of nitric oxide (NO) is induced in blood vessels by inflammatory stimuli as a result of the expression of the inducible form of NO-synthase (NOS-2). This happens in systemic inflammatory reactions like septic shock and in local reactions produced by endothelium denudation and atherosclerosis. NOS-2 activity in blood vessels may protect tissues by virtue of the vasodilating, anti-thrombotic and leukocyte adhesion inhibitory effects of NO. It may also participate in vascular remodeling as a result of the antiproliferative and pro-apoptotic actions of NO. However excessive production of NO in blood vessels is involved in circulatory failure that takes place in systemic inflammatory reactions and it may be cytotoxic for surrounding tissues. For these reasons, inhibition of NO overproduction has been proposed in the treatment of septic shock. Selective inhibitors of NOS-2 activity or NO trapping agent, or both, might prove to be valuable drugs in the treatment of some inflammatory diseases. The conditions in which NO shifts from a tissue protective to a damaging role are not well elucidated. Recent findings suggest that the interactions with superoxide radicals, thiols, and metals (particularly with Fe2+) may be important not only in buffering excess NO produced by NOS-2, but also in channeling it from physiologically to pathophysiologically relevant targets. It has also been found recently that adventitial cells may play an important part in vascular NO production and generation of NO stores in the media layer. The ultimate effect of NO in blood vessels might depend on its site of production, local concentration, and interactions with other tissue components.

Animals↗

Non-random distribution of blood vessels in the posterior region of the rat somatosensory cortex.

The quantitative distribution of blood vessels in the barrel region of somatosensory cortex of the rat was studied to determine the relationship of the vascular pattern to a functionally specialized cortical structure. Blood vessels were found to arborize in layers III and IV and to decrease in number toward layers I and VI, creating a spindle-shaped pattern through the cortex. The density of blood vessels was greater in the barrel core versus septal regions of layer IV. The distribution pattern of blood vessels within the barrel region was remarkably non-random and constant even between animals. The pattern was consistent enough to form a reliable set of landmarks with which to identify a specific barrel from light- to electron-microscopy transition.

Animals↗

Innervation of orbital and choroidal blood vessels by the pterygopalatine ganglion in pigeons.

Orbital and choroidal blood vessels in mammals are known to receive a parasympathetic innervation from the pterygopalatine ganglion, which appears to utilize vasoactive intestinal polypeptide (VIP) and nitric oxide (NO) to increase choroidal blood flow. The present studies were undertaken to elucidate the anatomical and neurotransmitter organization of the pterygopalatine ganglion input to orbital and choroidal blood vessels in pigeons. Single- or double-label immunohistochemistry were employed on paraformaldehyde-fixed cryostat sections of the pigeon eye and surrounding orbital tissue to localize 1) VIP+ neurons and fibers; 2) choline acetyltransferase (CHAT)-containing cholinergic neurons and fibers; 3) axons containing the 3A10 neurofilament-associated antigen; and 4) neuronal NO synthase (nNOS)-containing neurons and fibers. NOS+ neurons and fibers were also identified by NADPH-diaphorase histochemistry in sections and whole-mount specimens. The pterygopalatine ganglion was found to consist of an interconnected series of three to four main microganglia of about 50-200 neurons each and numerous lesser microganglia. The major microganglia of the pterygopalatine network in pigeon lie along the superior aspect of the Harderian gland, with many additional fibers and microganglia of the network encircling the gland. Neurons of all microganglia were extremely rich in VIP, nNOS, and NADPH-diaphorase and moderate in CHAT. The majority of the pterygopalatine ganglion neurons were observed to co-contain VIP and nNOS. Axons labeled for VIP, nNOS, NADPH-diaphorase, or the 3A10 antigen could be traced from the pterygopalatine ganglion network to perivascular fiber plexi on orbital blood vessels. These orbital vessels, many of which enter the choroid posteriorly and nasally, appear to be a conduit by which pterygopalatine postganglionic fibers reach the choroid. The pterygopalatine postganglionic fibers were also seen to innervate the Harderian gland and contribute branches to the nearby ophthalmic nerve. Within the choroid, VIP+ fibers were widely scattered and sparse but were most abundant in nasal choroid. A few VIP+ and NADPH- diaphorase+ neurons were also observed in the choroid. These results suggest that pterygopalatine ganglion neurons of birds use VIP and NO to exert vasodilatory control over blood flow to and within the avian choroid.

Animals↗

Role of neural guidance signals in blood vessel navigation.

Despite the tremendous progress achieved in both vasculogenesis and angiogenesis in the last decade, little is still known about the molecular mechanisms underlying the pathfinding of blood vessels during their formation. However, emerging evidence shows that different axonal guidance cues, including members of the Slit and semaphorin families, are also involved in the blood vessel guidance, suggesting that blood vessels and nerves share common mechanisms in choosing and following specific paths to reach their respective targets. These promising findings open novel avenues not only in vascular biology but also in therapeutic angiogenesis. Indeed, the identification of new molecules involved in the guidance of blood vessels may be helpful in designing angiogenic strategies, which would insure both the formation of new blood vessels and their guidance into an organized and coordinated network.

Animals↗

Relationship between catecholamine neurons and cerebral blood vessels studied by their simultaneous fluorescent revelation in the rat brainstem.

In order to study the relationship between catecholamine neurons and cerebral blood vessels, a technique was developed which permitted the simultaneous visualization of blue-green fluorescent catecholamine neurons and red fluorescent stained blood vessels in the brain of the normal rat. Sympathetic nerve fibers were found on the major arteries and in the pia-arachnoid at the base of the brainstem and also along paramedia and lateral perforating arteries as small as 10-12 microns within the brain. Running within the parenchyma, central catecholamine nerve fibers occasionally approached and intersected smaller blood vessels, either arterioles or venules of 8-12 microns, and infrequently climbed along or encircled these vessels for a limited distance, particularly within the lateral tegmentum. Across the nuclei of the brainstem, no overall contiguity of catecholamine terminals with capillaries was apparent, and no correlation between the density of catecholamine varicosities and that of capillaries existed. Only in regions with a high density of both catecholamine varicosities and capillaries, such as in the principal olivary nucleus, did a significant overlap of the two occur. But in most cases of moderately to densely innervated and vascularized regions, such as the solitary tract nuclei, the greatest concentration of terminals appeared over the parenchyma. Regarding the blood supply to the catecholamine neurons, their perikarya did not receive a particularly dense capillary supply relative to other nuclei. However, a special relationship of catecholamine cells to blood vessels was suggested, particularly in the case of dopamine neurons in the substantia nigra by the close apposition of cellular processes to adjacent small vessels. This morphological study was undertaken to determine whether central catecholamine neurons may significantly innervate cerebral blood vessels and accordingly, may function analogously to the peripheral sympathetic adrenergic neurons in the regulation of the vascular system. Although a limited number of associations between central catecholamine nerve terminals and small blood vessels suggested the possibility of an innervation in a few regions, the lack of an overall correspondence and correlation between the two across brainstem nuclei indicated that the analogy of central catecholamine neurons to the sympathetic nervous system was inappropriate. On the other hand, evidence of contact with vessels by presumed dendrites of the catecholamine neurons suggested a possible vascular sensory function.

Adrenergic Fibers↗

An ultrasonic needle guide for aiding percutaneous puncture of blood vessels.

An instrument which locates blood vessels by means of Doppler ultrasound and directs a needle at the located vessel has been developed. The feature of this instrument is that the needle does not pass down the ultrasonic beam as in other techniques that have been tried. Two transducers, mounted on sliding bars, are used to pin-point the vessel. The needle is then guided towards the intersection point of the two beams. Both the angle of entry and the point of incision of the needle can be chosen arbitrarily, while the transducers are kept well away from the needle and at an optimum angle to the skin.

Blood Vessels↗

Assembly and patterning of vertebrate blood vessels.

The mechanisms that regulate blood vessel assembly at appropriate sites in the organism are poorly understood, yet understanding this regulation is critical to the ability to design therapeutics around vessel production in vivo. Classic embryologic studies have yielded descriptive analyses of vascular pattern formation, and they show that angioblasts and endothelial cells respond to environmental cues to assemble at precise embryologic sites. The present study incorporated a genetic model, the mouse, into these studies to obtain mechanistic information regarding vessel assembly and patterning. The data show that both embryo-derived and stem-cell-derived mouse angioblasts respond to host cues in the avian embryo and pattern properly, and also highlight a critical role for the vascular endothelial cell growth factor signaling pathway in these patterning events.

Animals↗

Blood vessel diameter measurement by ultrasound.

Blood vessel diameter measurement is crucial to volume flow measurement in medical ultrasound. The accuracy of the measurement is examined in this study. Experiments were made on three kinds of tube using four transducers on three commercial duplex ultrasound scanners. The accuracy of the inner diameter measurement is affected by ultrasonic pulse length. By correcting this effect, it has been shown that the accuracy of the measurement can be increased significantly over a range of conditions.

Blood Vessels↗

The physiological significance of the endoendothelial fibrin lining (EEFL) as the critical interface in the 'vessel-blood organ' and the importance of in vivo 'fibrinogenin formation' in health and disease.

The author's theory of the endoendothelial fibrin lining (EEFL), first advanced in 1953 and developed by him ever since, localizes the homeostasis between steady fibrin formation and deposition, or 'fibrination', and continuous fibrinolysis in the more or less immobile portion of the plasmatic zone next to the vessel wall. In 1971, the author advanced, in relation to the EEFL, the theory of fibrinogen gel clotting without thrombin action or 'fibrinogenin' formation in vivo. Considerable direct and indirect experimental evidence, secured by the author and by several other investigators, advanced markedly the knowledge of the normal physiology and the pathophysiology of various disease processes involving the vessel wall and blood circulation. The information presented is an extension to that given in the author's recent overview (Clin. Hemorheology 1, 9-72, 1981). It deals both with new data by several investigators including those by the author, as well as with older data from the literature. The author maintained already in 1960 that the blood together with the blood vessels, in which it circulates, constitute 'an entity'. In 1981 he postulated this entity to be a very special organ, named conveniently 'vessel-blood organ', which is ubiquitous and penetrates all other organs and adjacent tissues. The EEFL of the vessel-blood organ is considered by the author as the crucial critical interface between the blood and the vessel wall. It is the primary barrier, followed by the endothelium (comprising the endothelial cells and the interendothelial cement substance which contains or is identical with 'cement fibrin') and the basement membrane for the exchanges between the blood, the vessel wall and its surrounding tissues and spaces. The EEFL acts as anticoagulant, is antithrombogenic, maintains vascular patency and aids cardiac action by decreasing significantly the apparent viscosity of blood, referred to in the literature as the 'Copley-Scott Blair phenomenon'. A new concept of leukocyte emigration traversing the capillary wall is presented, affecting focal fibrinolysis of the EEFL and of fibrin contained in the interendothelial cement substance and in the basement membrane. The physical property of capillary (or vascular) permeability is related to the existence of the EEFL, since, as found by Copley et al, both fibrinopeptides, liberated in the transition of fibrinogen to fibrin, and plasminopeptides, freed in the conversion of plasminogen to plasmin, enhance capillary permeability. Capillary fragility, which is antagonistic to capillary permeability, is in great part due to fibrinolytic action on fibrin as a constituent of the basement membrane.(ABSTRACT TRUNCATED AT 400 WORDS)

Basement Membrane↗

Chondroitinase ABC (pharmaceutical grade) for chemonucleolysis. Functional and structural evaluation after local application on intraspinal nerve structures and blood vessels.

STUDY DESIGN: The effects on nerve tissue and blood vessels of locally applied chondroitinase ABC were studied in two experimental models using chymopapain and the vehicle of chondroitinase ABC for controls. OBJECTIVES: To assess the effects of chondroitinase ABC on blood vessels and nerve tissue after local application. SUMMARY OF BACKGROUND DATA: Chondroitinase ABC has been suggested for chemonucleolysis because it has a high specificity for nucleus pulposus matrix, which could mean a high efficiency in dissolving disc tissue combined with a low risk of side effects on other tissues. METHODS: Chondroitinase ABC or controls were injected intrathecally in the pig, and nerve conduction velocity and histologic changes were assessed after 7 days. The same substances were injected into the hamster cheek pouch and studied for 60 minutes for microvascular effects. The vehicle for the enzyme was used as a negative control and chymopapain in a therapeutic concentration served as a positive control. RESULTS: In all series there was a slight intrathecal fibrotic reaction that was most pronounced after chymopapain injection. The effects on nerve conduction velocity and nerve morphology were similar between chondroitinase ABC and its vehicle. Chymopapain induced a significant reduction in nerve conduction velocity and pronounced histologic changes. In the cheek pouch, chymopapain induced a stand-still of blood flow at the injection site, and microhemorrhage and macromolecular leakage from the vessels at the border of the injection site. Only a slightly reduced blood flow was occasionally found after injection of chondroitinase ABC and controls. CONCLUSIONS: In agreement with the current literature, these observations indicate that chondroitinase ABC is safe regarding adverse effects on nerve tissue and blood vessels. The slight reduction in conduction velocity after intrathecal injection of chondroitinase ABC or its vehicle is most likely the result of surgical injury while releasing the nerve roots from the intrathecal fibrous adhesions. Such adhesions may be related to the laminectomy per se, and probably have no pathophysiologic significance.

Animals↗

Absorbed dose calculations to blood and blood vessels for internally deposited radionuclides.

At present, absorbed dose calculations for radionuclides in the human circulatory system used relatively simple models and are restricted in their applications. To determine absorbed doses to the blood and to the surface of the blood vessel wall, EGS4 Monte Carlo calculations were performed. Absorbed doses were calculated for the blood and the blood vessel wall (lumen) for different blood vessels sizes. The radionuclides chosen for this study were those commonly used in nuclear medicine. No penetration of the radionuclide into the blood vessel was assumed nor was cross fire between the vessel assumed. The results are useful in assessing the dose to blood and blood vessel walls for different nuclear medicine procedures.

Adult↗

Scanning electron microscopy of irradiated recipient blood vessels in head and neck free flaps.

Irradiated and control recipient blood vessels in a similar patient population were studied with scanning electron microscopy. The vessels that were biopsied were then anastomosed to a free flap. Irradiated arteries display a significantly greater wall thickness and higher incidence of intimal dehiscence compared with control arteries. Fibrin deposition, microthrombi, and endothelium cell dehiscence are present more frequently in irradiated vessels than in control vessels. Details of the preparation and anastomotic technique for irradiated blood vessels are discussed. Microvascular surgery in irradiated human blood vessels carries with it a higher risk of thrombosis due to preexisting vessel wall damage. This risk can be minimized by experience and attention to detail.

Arteries↗

Localization and expression of tissue kallikrein and kallistatin in human blood vessels.

Tissue kallikrein releases kinins by specific proteolysis, an activity inhibited by kallistatin. In this study, kallikrein and kallistatin were localized to endothelial and smooth muscle cells of large, medium, and small normal blood vessels by immunohistochemical techniques. Immunostaining for both proteins was strong in the endothelium of all sizes of blood vessels and was more intense in medial smooth muscle cells of small and medium-sized blood vessels than in elastic arteries. The sites of synthesis by endothelial and smooth muscle cells were demonstrated in normal blood vessels of all sizes by in situ hybridization histochemistry. Kallikrein and kallistatin levels were measured by immunoassays in homogenates of human aorta, vena cava, and iliac artery and vein. Tissue kallikrein and kallistatin transcripts were identified in human blood vessels by RT-PCR followed by Southern blot analysis with specific oligonucleotide probes. The results demonstrated the expression and co-localization of tissue kallikrein and kallistatin in human vessels and suggest a potential role of kallistatin in regulating tissue kallikrein in blood vessels.

Blood Vessels↗