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The representation of retinal blood vessels in primate striate cortex.

The blood vessels that nourish the inner retina cast shadows on photoreceptors, creating "angioscotomas" in the visual field. We have found the representations of angioscotomas in striate cortex of the squirrel monkey. They were detected in 9 of 12 normal adult animals by staining flatmounts for cytochrome oxidase activity after enucleation of one eye. They appeared as thin profiles in layer 4C radiating from the blind spot representation. Angioscotomas can be regarded as a local form of amblyopia. After birth, when light strikes the retina, photoreceptors beneath blood vessels are denied normal visual stimulation. This deprivation induces remodeling of geniculocortical afferents in a distribution that corresponds to the retinal vascular tree. Angioscotoma representations were most obvious in monkeys with fine ocular dominance columns and were invisible in monkeys with large, well segregated columns. In monkeys without columns, their width corresponded faithfully to the inducing retinal shadow, making it possible to calculate the minimum shadow required to produce a cortical representation. The "amblyogenic threshold" was calculated as the fraction of the pupil area eclipsed to trigger remodeling of geniculocortical afferents. It was found to be constant over retinal eccentricity, vessel size, and shadow size. Ambliogenic shadows only three to four cones wide were sufficient to generate a cortical representation, testifying to the remarkable precision of the cortical map. The representations of retinal blood vessels separated by only 0.65 degrees were resolvable in the cortex, yielding an upper limit on cortical resolution of 340 microm in layer 4C.

Animals↗

A new device for the detection and recognition of blood vessels in laparoscopic surgery.

BACKGROUND: The recognition and localization of blood vessels to prevent their intraoperative perforation poses a major problem in laparoscopic surgery. The endoscopic pulse detector is a new device that has been specially developed for the detection and recognition of blood vessels in laparoscopic surgery. The instrument uses an accelerometer to detect a pulse, and it is inexpensive and simple to use. The aim of this study was to investigate the performance and possibilities of the new instrument. METHODS: The instrument's performance and features were tested in laboratory conditions by use of simulated circulation. We assessed the dependence of the signal amplitude recorded by the instrument over a given blood vessel on the blood pump frequency change (36-130/min), circulating systolic pressure change (40-180 mm Hg), and adjacent blood vessel pulsations. Clinically, the instrument was tested in a randomized study in 40 elective noncomplicated laparoscopic cholecystectomies, where we assessed the time needed for the preparation of Calot's triangle and positioning of the cystic artery. RESULTS: The results of laboratory testing showed that the instrument operated throughout the frequency range of 36-130/min and a circulating systolic pressure range of 40-180 mmHg, while the signal amplitude rose with pressure increase. The results of clinical testing showed that use of the pulse detector in laparoscopic cholecystectomy significantly reduced the time needed to prepare Calot's triangle (t = 3.91; df = 38; p <0.001) and also made the positioning of the cystic artery more reliable. CONCLUSION: The study showed the new instrument to be very simple to use and potentially valuable in laparoscopic surgery, primarily for the differentiation of blood vessels of similar structures.

Arteries↗

Compartmentalized mast cell degranulations in the ovarian hilum, fat pad, bursa and blood vessel regions of the cyclic hamster: relationships to ovarian histamine and blood flow.

Ovaries from hamsters on each day of the oestrous cycle at 09.00 h were observed for the number of mast cells, the pattern of mast cell degranulation, histamine concentration and blood flow. On day 4 (pro-oestrus), ovaries were also observed at 9.00, 15.00 and 21.00 h. Mast cell degranulation was evaluated by 3 criteria: (1) no degranulation = less than 5 granules dispersed from the cell; (2) moderate degranulation = 5 or more granules dispersed but less than 15, and (3) extensive degranulation = 15 or more granules released. Blood flow was determined using radio-active microspheres in anaesthetized animals. Mast cells were observed in fat pad (beyond 2 mm of the bursal mesothelium), bursa (within 2 mm of the bursal mesothelium), hilum and near ovarian blood vessels (these 4 regions are collectively called the ovarian complex). The distribution of ovarian mast cells was not uniform. Most mast cells were near ovarian blood vessels (42.2%) and in the fat pad (37.2%). A moderate number of cells were in the bursal wall (20%) and only a few cells were observed in the hilum (0.64%). Mast cell number remained unchanged on days 1-4 of the cycle in each ovarian compartment. However, summation of the number of mast cells in the entire ovarian complex revealed a significant decline in number at 15.00 h on pro-oestrus. Alterations in mast cell degranulation were primarily restricted to 2 periods of the cycle (pro-oestrus and di-oestrus). An increase in moderate but not extensive degranulation was observed in only the fat pad and bursa on day 2 when compared with day 1 values. In most ovarian compartments on pro-oestrus, degranulation was higher than on any other day of the cycle. At 15.00 h on pro-oestrus, extensive degranulation in bursa, fat pad and blood vessel regions (but not hilum) coincided with an increase in ovarian histamine and decline in number of mast cells; ovarian blood flow also increased at the time but remained unchanged the remainder of the cycle.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

NO mediates mural cell recruitment and vessel morphogenesis in murine melanomas and tissue-engineered blood vessels.

NO has been shown to mediate angiogenesis; however, its role in vessel morphogenesis and maturation is not known. Using intravital microscopy, histological analysis, alpha-smooth muscle actin and chondroitin sulfate proteoglycan 4 staining, microsensor NO measurements, and an NO synthase (NOS) inhibitor, we found that NO mediates mural cell coverage as well as vessel branching and longitudinal extension but not the circumferential growth of blood vessels in B16 murine melanomas. NO-sensitive fluorescent probe 4,5-diaminofluorescein imaging, NOS immunostaining, and the use of NOS-deficient mice revealed that eNOS in vascular endothelial cells is the predominant source of NO and induces these effects. To further dissect the role of NO in mural cell recruitment and vascular morphogenesis, we performed a series of independent analyses. Transwell and under-agarose migration assays demonstrated that endothelial cell-derived NO induces directional migration of mural cell precursors toward endothelial cells. An in vivo tissue-engineered blood vessel model revealed that NO mediates endothelial-mural cell interaction prior to vessel perfusion and also induces recruitment of mural cells to angiogenic vessels, vessel branching, and longitudinal extension and subsequent stabilization of the vessels. These data indicate that endothelial cell-derived NO induces mural cell recruitment as well as subsequent morphogenesis and stabilization of angiogenic vessels.

Animals↗

Permeability properties of tumor surrogate blood vessels induced by VEGF-A.

Malignant tumors generate new blood vessels by secreting growth factors, particularly members of the vascular permeability factor/vascular endothelial growth factor (VPF/VEGF) family. Overall, the new blood vessels that form are hyperpermeable to plasma proteins, a property that is thought to be important for generating new stroma. However, tumor blood vessels are structurally heterogeneous and include microvessels of at least the following distinct types: mother vessels (MV), glomeruloid microvascular proliferations (GMP), arterio-venous-like vascular malformations and capillaries. Our goal was to determine whether macromolecular tracers leaked from all or from only a subset of these vessel types and to elucidate the extravasation pathways. As blood vessels are only a minor component of tumors, and therefore, difficult to study in situ, we used an adenoviral vector to express VEGF-A164, the most important member of the VPF/VEGF family, in mouse tissues. So expressed, VEGF-A164 induces large numbers of surrogate vessels of each type found in tumors in a highly reproducible manner. Overall permeability to plasma proteins was assessed qualitatively with Evan's blue dye and quantitatively with a dual tracer method employing radioactive albumin. Leaky vessels were identified by confocal microscopy (FITC-dextran) and by electron microscopy (ferritin). MV, and to a lesser extent GMP, were found to be hyperpermeable but capillaries and vascular malformations were not. Ferritin extravasated primarily by two trans-cellular routes, vesiculo-vacuolar organelles (VVOs) and fenestrae. This occurred despite a considerable reduction in VVO frequency as VVO membranes translocated to the plasma membrane during MV formation. However, reduction in the number and complexity of VVOs was offset by extensive endothelial cell thinning and a greatly shortened extravasation pathway. Extrapolating these findings to tumors predicts that only a subset of tumor vessels, MV and GMP, is hyperpermeable, and that measures of overall vessel permeability greatly underestimate the permeability of individual MV and GMP.

Animals↗

Characterization of glutamic acid decarboxylase activity in cerebral blood vessels.

Glutamic acid decarboxylase activity associated with cerebral blood vessels appears to be part of a specific cerebrovascular system involving gamma-aminobutyric acid. This activity was characterized kinetically and pharmacologically and compared with that in brain and several nonneuronal tissues. Formation of gamma-aminobutyric acid from [14C]glutamate was measured in a soluble extract of pia-arachnoid blood vessels isolated from bovine brain. The vascular activity was like brain glutamate decarboxylase in that it required pyridoxal phosphate, was completely inhibited by aminooxyacetic acid, and had a similar affinity for glutamate. Cerebrovascular decarboxylase activity differed, however, from brain decarboxylase in that it was less sensitive to sulfhydryl reagents, was stimulated by 3-mercaptopropionic and cysteic acids, and was competitively inhibited by cysteine sulfinic acid. The glutamate decarboxylase activity of the cerebral vessels was similar to that in renal cortex and mesenteric blood vessels in its responses to sulfhydryl reagents and 3-mercaptopropionic acid. These findings are consistent with previous suggestions of a nonneuronal form of the enzyme and offer the possibility that synthesis of gamma-aminobutyric acid in cerebral blood vessels can be manipulated independently from that in neuronal tissue.

Animals↗

Blood vessel invasion and axillary lymph node involvement as prognostic indicators for human breast cancer.

Blood vessel invasion and axillary lymph node involvement were examined in 175 breast cancer patients. The incidence of blood vessel invasion was 35%. The presence of blood vessel invasion was highly associated with early disease recurrence. The association of poor prognosis with blood vessel invasion was independent of clinical stage, menopausal status, node status, tumor size, or postsurgical treatment. Those patients with blood vessel invasion and two or more positive nodes were at extremely high risk for early recurrence (70% recurrence by two years compared with 15% recurrence in the remainder of the patients). Thus, blood vessel invasion is a useful indicator of early recurrence in patients with primary breast cancer and, in combination with node status, is a prognostic indicator with high discriminatory power.

Axilla↗

Permeability and patency of retinal blood vessels in experimental diabetes.

Increased permeability of retinal blood vessels in human diabetic retinopathy is well known clinically. Its morphologic equivalent is unknown. In dogs with 5 years of poorly controlled alloxan diabetes and nonproliferative diabetic retinopathy comparable to that of man, permeability and patency of retinal blood vessels were tested with the protein tracer horseradish peroxidase and evaluated by electron microscopy. A breakdown of the blood-retinal barrier was found associated with extensive tracer leakage around retinal blood vessels. Tracer had seemingly permeated endothial junctions, and was not transported through the endothelial cytoplasm. Blood vessels which had lost their endothelial cells and were partially occluded by glial cells retained some patency to tracer. These findings suggest the following. (1) Endothelial tight junctions are not a static cell specialization but one that can open due to chronic metabolic or osmotic factors prevailing in diabetes. Opened tight junctions may account for plasma leakage seen clinically in human diabetic retinopathy. (2) In the absence of endothelial cells perfusion does not necessarily end abruptly. The tracer method and electron microscopy may show details of vascular obstruction that are not readily demonstrated clinically.

Animals↗

Correlation between the number of epineurial and endoneurial blood vessels in diseased human sural nerves.

In a preceding study it was shown that changes in the number of epineurial blood vessels may be a prominent feature in angiopathic and other peripheral neuropathies, for instance in vasculitis, diabetes mellitus, or cerebral autosomal dominant angiopathy with multiple infarcts and leukoencephalopathy (CADASIL). Endoneurial blood vessels usually may also show significant structural alterations in a broad spectrum of neuropathic conditions, although these are not as prominent as in the epineurium. However, the relationship between changes in the number of epineurial and endoneurial blood vessels in diseased human sural nerves, and the impact of the loss of myelinated nerve fibers on the number of endoneurial blood vessels has thus far not been determined. Therefore, we investigated and compared the number of epineurial and endoneurial blood vessels in 50 human sural nerve biopsy specimens, representing a variety of peripheral neuropathies. We found that despite a significant increase of the number of epineurial blood vessels in cases with vasculitic neuropathy (P<0.05) and neuropathy with other types of microangiopathy (P<0.01), the number and density of the endoneurial blood vessels remained remarkably constant. In cases with an axonal type of neuropathy, severe neuropathic changes were associated with a decreased epineurial blood vessel number and a simultaneous, relative increase in the endoneurial blood vessel density. No significant correlation was found between (1) the number of epineurial and endoneurial blood vessels, and (2) the severity of the neuropathy and the number or density of epineurial and endoneurial blood vessels.

Adolescent↗

Hybrid concept on the mechanical test method of small caliber blood vessel.

A mechanical test on small caliber blood vessel is difficult because the strength is very low and the dimension is very small. In the present paper a multifunctional axial test apparatus design is proposed. This has the characteristics such that the load cell and the environmental container for the specimen are built up in terms of cassette, respectively, and thus both are easy to equip and take off, that is, easy to replace. Also, the test methodology by internal pressure for small caliber blood vessels has been proposed. By using both of these methodologies, the characteristics of the mechanical behavior of small caliber blood vessels, such as compliance, stress relaxation, and viscoelastic property have been clarified. An attempt has been made on the application of this method to a clinical case.

Anastomosis, Surgical↗

[Clinical research on arteriovenous internal fistula made by various blood vessels].

OBJECTIVE: To compare the permeability and incidence rate of complication of arteriovenous internal fistula made by autogenous, homologous, and artificial Teflon blood vessels. METHODS: Two hundred and forty one cases with arteriovenous internal fistula made by autogenous, homologous, and artificial Teflon blood vessels were followed up to compare the permeability and incidence rate of complication at 6 months, 1 year, 3 years, and 5 years. RESULTS: The incidence rate of complication of autogenous blood vessels was lowest, it had no statistical differences compared with arteriovenous internal fistula made by homologous blood vessels. The permeability of arteriovenous internal fistula made by homologous blood vessels was highest, and it had no statistical differences compared with autogenous blood vessels. The permeability of arteriovenous internal fistula made by artificial Teflon blood vessels was lowest, but the incidence rate of complication was highest, and it had significantly statistical differences compared with arteriovenous internal fistula made by autogenous blood vessels (P < 0.01). CONCLUSION: Arteriovenous internal fistulas made by autogenous and homologous blood vessels have high permeability and low incidence rate of complication, they are superior to the arteriovenous internal fistula made by artificial Teflon blood vessels.

Adolescent↗

Concomitant immunocytochemical study of macrophage cells and blood vessels in disc herniation tissue.

Twenty disc herniations (DH) were studied immunocytochemically for macrophages and blood vessels. Serial thin frozen sections were immunostained with an antibody specific for tissue macrophages (monoclonal antibody to CD68 antigen) and the endothelium of blood vessels (polyclonal antibody to von Willebrand factor). With this method, blood vessels, often abundant, were observed in as many as 16/20 (80%) of the DH studied, 12 disc extrusions and 8 sequestrated discs, whereas abundant macrophages were noted in 11/20 (55%) of the DH. Macrophages were present only in areas with blood vessels and had presumably infiltrated the tissue from them. As has been noted previously, some blood vessels are apparently newly formed as a result of tissue injury, whereas others were present in the disc prior to herniation. This is suggested by the lack of a clear correlation between the presence or absence of blood vessels and the preoperative duration of radicular pain. In areas of the DH where cartilage fragments occurred, both macrophages and blood vessels were particularly abundant.

Adult↗

Blood vessel coagulation for incisional surgery.

Blood vessel electrocoagulation allows the cutaneous surgeon rapid and reliable bleeder control for incisional wounds. The following article discusses the various instruments and techniques used for blood vessel electrocoagulation.

Electrocoagulation↗

Vascular invasion of O-1N, hamster squamous cell carcinoma with high potential of lymph node metastasis: ultrastructural comparison between lymphatics and blood vessels.

The ultrastructural modes of lymphatic and blood vessel invasions were studied comparatively in hamsters with squamous cell carcinoma (O-1N) that had a high potential for lymph node metastasis. The endothelial injury, which was caused by mechanical stretching with the growth of O-1N, was the initial and characteristic feature common to both vascular invasions. Tumor cell nests penetrating the lymphatic lumen through disrupted endothelial cells still maintained their volume and continuity to the underlying tumor cell nests. In contrast, pronounced microthrombotic and neutrophilic reactions occurred at the site of blood vessel penetration. Within the lymphatic lumen, large clusters of O-1N cells were kept longer in spite of lymphocytic and macrophagic reactions. In blood vessels, clusters of tumor cells that had passed through dense fibrin layers were reduced in size and further disintegrated into smaller pieces by neutrophils. In conclusion, lymphatic invasion is a mechanical process, and smooth and direct invasion of large tumor cell nests into lymphatic vessels is responsible for causing more prompt and frequent lymph node metastasis in O-1N than a hematogenous type.

Animals↗

[Spontaneous rhythmic contractions of human placental vessels: is it an evidence for a physiological pacemaker in blood vessels?].

BACKGROUND: Placental vessels are not innervated. Therefore the vasomotor activity and vascular tone is not regulated by the nervous system. AIM: To assess the existence of pacemaker mechanisms related to rhythmic motor activity of blood vessels. MATERIAL AND METHODS: Isometric contractions of rings from umbilical and chorionic vessels of term human placentas were monitored. RESULTS: Recordings of the circular layer of chorionic and umbilical vessels revealed rhythmic spontaneous contractions with a frequency of 1.4 +/- 0.05 cycles/min, the duration of each cycle was 42.8 +/- 0.24 s (n = 12). The amplitude of contractions was larger in veins than in arteries, predominating in umbilical vein biopsies, proximal to the fetus. Both the frequency and the amplitude of contractions were relatively constant during the first 30 min. However, after an hour, the frequency declined while the amplitude increased. The absence of the endothelium neither modified the frequency nor the amplitude of the rhythmic activity. Blockage of voltage dependent sodium channels or calcium channels did not alter the frequency of spontaneous contractions, although their magnitude was reduced. Glibenclamide, an ATP-dependent K+ channel blocker or the blockade of gap junctions ablated the frequency and amplitude of spontaneous contractions. CONCLUSIONS: We propose that rhythmic contractions are triggered by pacemaker cells located in the circular layer of the smooth muscle of blood vessels and spread via gap junctions; they likely contribute to the control of blood flow.

Biological Clocks↗

Effects of off-centering on dose uniformity along and around blood vessels undergoing catheter-based intravascular brachytherapy.

PURPOSE: In intravascular brachytherapy, either photon or beta emitters are often used in a linear arrangement so that blood vessels of lengths in the range of several centimeters can be treated. With a line source, the dose uniformity and the range of doses that various components of the blood vessels receive depend not only on the type of radionuclides used in the treatment but also on the geometric position of radioactive source relative to the blood vessel walls. The aim of this study is to investigate the dose uniformity around the blood vessel and the effects on the uniformity due to the changes of the off-centering of different photon and beta emitters within the lumen. MATERIALS AND METHODS: Dose distributions were calculated on a cylindrical blood vessel of various radii. The radioactive sources of (192)Ir, (125)I, (103)Pd, (188)Re, (32)P, and (90)Y/Sr were studied. All the sources were assumed to be in the form of a line and had a length of 2 cm. The dose rate at a point in space produced by a radioactive source was computed by integrating the point dose rate kernel of the corresponding radionuclide over the 2-cm-long radioactive line. The point dose rate kernel was computed with Monte Carlo simulation of radiation transport. Dosimetric calculations were performed for both concentric and nonconcentric radioactive line source locations. Off-centering effects on the dosimetry were characterized with two newly defined quantities LDU and ADU: LDU describes the longitudinal dose uniformity along blood vessels and ADU describes the azimuthal dose uniformity, i.e., the dose deviation from the expected delivery dose around blood vessels. RESULTS: The longitudinal dose uniformity did not change significantly with the off-center distance. The azimuthal dose uniformity around the blood vessel deteriorated as the off-center distance increased. The ADU was worse for nonconcentric beta emitters than the photon emitters. For example, if the off-center distance was 1 mm and the radial distance was 1.5 mm, the range of dose around the blood vessel on the central transverse plane (normalized to the corresponding dose under the concentric condition) was from 0.55 to 3.3, 0.56 to 3.3, 0.53 to 3.4, 0.43 to 6.0, 0.38 to 4.3, and 0.31 to 4.7 for (192)Ir, (125)I, (103)Pd, (90)Y/Sr, (188)Re, and (32)P sources, respectively. However, it appeared that there existed a lower limit of underdosing (about 40% of desired delivery dose) caused by the off-centering for the photon emitters. It was also found that both ADU and LDU became almost independent of source length when the length was longer than or equal to 20 mm. CONCLUSIONS: A generalized formalism for expressing the dose uniformity along and around blood vessels generated with a linear source was developed and used to study the longitudinal and azimuthal dose uniformity for different types of radionuclides. Although concentric beta emitters provide uniform dose coverage along blood vessels, nonconcentric beta emitters produced larger dose deviations and worse dose uniformity around the blood vessels than photon emitters. The off-centering introduced significantly higher dose on proximal vessel walls for both beta and photon emitters; however, the underdosing at distal points due to off-centering was somewhat limited for the high-energy photon emitters. The magnitude of off-centering effects for the low-energy photon emitters ((103)Pd) was less than that for beta emitters but more than that for higher energy photon emitters ((125)I and (192)Ir).

Beta Particles↗

The effect of diameter ratio between vascular substitute and blood vessel on anastomosis.

It is necessary to maintain mechanical compatibility between a blood vessel and a vascular substitute to promote encapsulation around the anastomosed part. From this point of view, using linear elastic theory, we had previously performed stress analyses at the part anastomosed by tissue adhesion, in order to propose some methods of preventing stress concentration at this junction. In this study, based on the previous analyses, we have attempted to develop a concept that can be applied under the conditions of operation. That is, the initial diameter of a vascular substitute with high rigidity is chosen larger than that of a blood vessel. This will reduce the stress concentration around the anastomosed part, on average, during expansion of the blood vessel. We analysed the optimum diameter ratio between the vascular substitute and the blood vessel which causes the least stress concentration, on average, during this process, using linear elastic theory. Furthermore, numerical analyses of blood vessel deformation were performed using various nonlinear stress-strain laws. These results were compared to the analytical solution based on linear elastic theory.

Anastomosis, Surgical↗

Skin blood vessels are simultaneously innervated by sensory, sympathetic, and parasympathetic fibers.

Despite the known major role of skin blood vessel innervation in blood flow control, particularly in disease, little information on the co-innervation of blood vessels by sensory and autonomic fibers and the relationships of these fibers to one another is available. To fill this gap, we performed a light and electron microscopic analysis of the innervation of skin vessels by sensory and autonomic fibers by using the rat and monkey lower lips as a model. In rats, double-labeling immunocytochemistry revealed that combinations of fibers immunoreactive for substance P (SP) and dopamine-beta-hydroxylase (DbetaH), SP and vesicular acetylcholine transporter (VAChT), as well as DbetaH and VAChT occurred only around blood vessels in the lower dermis. All fiber types travelled in parallel and in close proximity to one another. In the upper dermis, blood vessels were innervated by SP-containing fibers only. Although nerve terminals displayed synaptic vesicles, synaptic specializations were never observed, suggesting that, in this territory, these fibers do not establish synaptic contacts. Quantification of the distance between the various immunoreactive terminals and their presumptive targets (smooth muscle cells and endothelial cells) revealed that both sympathetic and parasympathetic fibers were significantly closer to the endothelial cell layer and smooth muscle cells compared with sensory fibers. In monkeys, double-labeling immunocytochemistry was performed for SP-DbetaH and SP-VAChT only. The results obtained are similar to those found in rats; however, the fiber density was greater in monkeys. Our findings suggest that the regulation of skin microcirculation might be the result of the coordinated functions of sensory and autonomic fibers.

Animals↗