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PubMedDate not supplied

[Changes of blood flow structure in precapillary microvessels during significant slow-down of flow].

The experiments were carried out with a special "biological model" in which the rabbits' red blood cell suspension possessing low hematocrit circulated in frogs' mesenterial microvessels. Red blood cell behaviour was investigated in microvessels of 19-45 microns in diameter under conditions of arbitrarily changed flow velocity in mesenterial microvessels. Automatic frame-to-frame analysis of cinematographic films with the texture analysis system (Ernst Leitz, FRG) showed that the velocity fluctuations of individual red blood cells and their radial displacements increased significantly, while their velocity profile became blunt, during slowing-down of flow from 0.7 to 0.2 mm/s. Thus the normal blood flow structure in microvessels becomes disordered under ischemic conditions entailing disturbance of blood rheological properties and creating additionally increased resistance in the vessels.

Animals↗

PubMed1990

[Age-related dynamics of energy metabolism enzymes of neurons and microvessels of the brain in spontaneously hypertensive rats].

The age changes in the activity of some enzymes in neurons and in microvessels, revealed histochemically, as well as the volume of microvessels in spontaneously hypertensive (SH) rats differ from these changes in the controls. At the age of 3 months the activity of these enzymes and the number of active microvessels in SH rats increased. At the age of 6 months the activity of studied enzymes in SH rats decreased, while the number of active microvessels remained constant. The correlation between the morpho-functional characteristics of brain tissue in SH rats and its greater ischemic vulnerability is assumed.

4-Aminobutyrate Transaminase↗

PubMed1989

Alterations in adrenergic receptors of frontal cortex and cerebral microvessels in Alzheimer's disease and aging.

Biochemical and pathological abnormalities are evident in the noradrenergic innervation of the cerebral cortex in Alzheimer's Disease (AD), and there is also a decline in aging, which may lead to changes in adrenergic receptors. To assess this question, we analyzed adrenergic receptor subtypes by ligand binding methods in prefrontal cortex and brain microvessels from subjects with AD and aging controls. Ligand binding to adrenoceptors and their subtypes did not change with postmortem delay in obtaining tissues. alpha 1-adrenergic receptors of the frontal cortex did not correlate with age but there was a small (approximately 25%), though significant, reduction in AD subjects. In cerebral microvessels, there were no changes in these receptors. alpha 2-receptors of the cortex significantly declined with age in controls and were also significantly reduced by approximately 50% in AD subjects. However, in cerebral microvessels alpha 2-adrenergic receptors were significantly increased by approximately 60% in AD. We suggest that presynaptic alpha 2-adrenoceptors on noradrenergic synapses may be those that are selectively decreased in the prefrontal cortex in AD. Total beta-receptors in cortex did not correlate with age, nor were they altered in AD. However, beta 1-receptors were decreased but beta 2-receptors were significantly increased in AD, indicating a change in the relative ratio of beta 1/beta 2-receptors. Similarly, beta 2-receptors of cerebral microvessels were significantly increased in AD. These changes suggest receptor "up-regulation" in response to noradrenergic denervation in AD and may reflect functional changes at the blood-brain barrier.

Adult↗

PubMed1988

On the mechanisms underlying 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine neurotoxicity. II. Susceptibility among mammalian species correlates with the toxin's metabolic patterns in brain microvessels and liver.

Systemic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causes parkinsonism in humans and other primates, but not in rats; mice are intermediate in their susceptibility which varies among strains. We hypothesized previously that the rat's resistance to systemic MPTP toxicity is likely due to the unique enrichment of its blood-brain barrier with enzymes that metabolize MPTP. MPTP metabolites, such as 1-methyl-4-phenylpyridinium (MPP+) and 1-methyl-4-phenyl-2,3-dihydropyridinium, may have difficulty in traversing biological membranes and reaching the brain sites of toxicity. We tested this hypothesis by studying MPTP metabolism: 1) in vitro, by human, rat and mouse brain microvessels and 2) in vivo, in the brain and liver of Wistar rats and two strains of mice known to react differently to systemic MPTP. We found that rat brain microvessels were very efficient at converting MPTP to MPP+ and that this conversion was abolished by pargyline. Microvessels from C57 black mice, which are more sensitive to MPTP toxicity than CF1 white mice, were less capable of metabolizing MPTP to MPP+. Human microvessels were least capable of producing MPP+. In vivo metabolism of MPTP in Wistar rats and the two strains of mice showed that the clearance of MPTP and its metabolites from the brains was most rapid in rats, intermediate in white mice and slowest in black mice. On the other hand, liver metabolism of MPTP by the three groups of animals showed a high rate of MPTP metabolism to a compound(s) other than MPP+ in rats, and a lower rate in mice.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMed1987

Effects of asphyxia on telencephalic microvessels of premature beagle pups.

The authors identified alterations in the brain microvasculature of the premature Beagle pup that could be attributed to asphyxia and potentially associated with the etiology of intraventricular hemorrhage (IVH). Beagle pups were delivered by cesarean section six days before their predicted whelping date and exposed to an alternating protocol of asphyxial episodes known to produce IVH. Data from the telencephalic microvasculature at both the germinal matrix (an area susceptible to IVH) and the borderzone cerebral cortex (an area rarely involved in hemorrhage) were analyzed. The germinal matrix microvessels responded differently to asphyxia than the cortical vessels. The germinal matrix microvessels maintained junctional complexes and intraluminal microvilli, and increased in cross-sectional luminal area following asphyxia; however, total vessel cross-sectional area did not change. After the asphyxial insult, cortical microvessels no longer exhibited intraluminal microvilli and increased in both total cross-sectional area and luminal area. The number of junctional complexes in cross-sections of cortical vessels was significantly reduced due at least in part to the narrowing of the endothelial cell lateral borders. The data provide indirect evidence to substantiate vasodilation speculated to be due to an increased cerebral blood flow to telencephalic vessels (both the germinal matrix and cerebral cortex) following asphyxia. The data also suggest differential rates of maturation between germinal matrix and cortical microvessels.

Animals↗

PubMed1987

Blood flow fluctuations in cerebral cortex microvessels.

Studies on the dynamics of the blood flow in cerebral microvessels with the diameter of erythrocyte flow (5-13 micron) carried out by the cinema-TV method showed that the linear velocity of the blood flow in microvessels experienced considerable fluctuations the amplitude of which varied within 10 to 1500 micron/s and the period within 0.2 to 7 s. It was established that variations in linear velocity of the blood flow were most frequently observed during 0.5-1 s. The autocorrelation analysis showed there was periodicity in the blood flow fluctuations in most microvessels which varied within a wide range of 0.3 to 3 s. A linear dependence was found between the amplitude and the period of fluctuations. The observed variations in the blood flow are likely to be caused by the changes in local resistance when leukocytes and erythrocyte aggregates passed through microvessels.

Animals↗

PubMed1984

[Blood flow fluctuations in the microvessels of the rat temporal muscle].

Dynamic characteristics of the blood flow linear velocity in microvessels on the surface of rat's temporal muscle were determined by means of accelerated cinemicrography. The blood flow velocity varied from 200 to 5000 microseconds in microvessels with diameter 4-13 mu. The blood flow fluctuated with period of 0.3-7.0 sec and amplitude 0.5-100% of the average. Auto- and crosscorrelation analysis showed a positive interrelationship between velocities shifted in time by 0.5 sec in 37% of the cases. The interrelationships did not exist between rapid changes of the blood flow in either adjacent or distant microvessels. The sharp blood flow changes seem to be due to periodical passage of leucocytes and aggregated erythrocytes which increases the resistance of blood current in the microvessels.

Animals↗

PubMed1983

[Blood flow in the microvessels of the cerebral cortex].

To measure dynamic characteristics of linear velocity of the blood flow in microvessels on the surface of rat's brain, the method of accelerated cinemicrography was used. The blood flow velocity varied from 500 to 5000 mu/sec in microvessels with diameter of 7-15 mu. The blood flow fluctuated with the rate of 1-3 oscillations per second and the amplitude 20-50% of the average value. Auto- and crosscorrelation analysis of the processes revealed in 35% of the cases a positive correlation between shifts of velocities and the frequency of their occurrence. No correlation existed between rapid changes of the blood flow in adjacent or distant microvessels. The sharp changes of blood flow seem to be due to periodical passage of leucocytes and accumulated erythrocytes which increase resistance against the blood flow in microvessels.

Animals↗

PubMed1983

Brain microvessels take up large neutral amino acids in exchange for glutamine. Cooperative role of Na+-dependent and Na+-independent systems.

Some regulatory aspects of neutral amino acid transport were investigated in isolated brain microvessels, an in vitro model of the blood-brain barrier. Preloading of the microvessels with glutamine stimulated the subsequent uptake of other neutral amino acids by way of the Na+-independent L system, but had no effect on the uptake of either basic or acidic amino acids. Moreover, this stimulation was abolished when the loading step was carried out in the absence of Na+ ions or in the presence of a high concentration of alpha-methylaminoisobutyric acid, indicating that the microvessels were able to concentrate glutamine via the A system of amino acid transport. Since the presence of the A system of neutral amino acid transport has not been detected in studies of blood-brain transport performed in vivo, the A system is probably associated with the antiluminal side of brain microvessels. Our results indicate, therefore, that the concentrative Na+-dependent A system and the exchanging Na+-independent L system can cooperate in the uptake of the large neutral hydrophobic amino acids. Such a cooperation may be relevant in the pathogenesis of some neurological disturbances such as hepatic encephalopathy, in which brain glutamine concentration is unusually high.

Amino Acids↗

PubMed1982

[Functional and morphological characteristics of rat liver microvessels in hypokinesia].

The investigation was carried out on 86 white non-inbred male rats. Hypokinesia was produced by putting the animals into pencil-boxes for 1,2 and 4 weeks. The changes in specific volumes of various hepatic microvessels under hypokinesia and under hypokinesia combined with metyrapone administration were studied sterologically. NAD-diaphorase activity in hepatocytes and in the interlobular connective tissue was estimated photometrically. hypokinesia produces certain changes in the specific volume of all the hepatic microvessels studied, but the degree and character of the volumetric relations revealed between these microvessels are different. At metyrapone administration, the volumetric changes in various microvessels occur with greater regularity. The changes in NAD-diaphorase activity under the same conditions occur slower and by the end of the experiment the enzymatic activity returns to the initial level.

Adrenal Glands↗

PubMed1982

[Velocity profiles in the microvessels dependent on the velocity and concentration of erythrocytes].

Distribution of velocities of erythrocytes dependent upon their distance from the vascular axis were studied in 25-40 mu large microvessels of the frog mesentery. The method of in vivo cinemicrography with subsequent analysis revealed that with a mean axial velocity of blood flow higher than 0.3-0.4 mm/sec the velocity profile was parabolic, similar to the laminar flow of Newtonian fluids and independent of the erythrocytes concentration in microvessels. With velocities less than 0.3-0.4 mm/sec a chaotic distribution of erythrocytes velocities occurred and the parabolic form of the velocity profiles was rarely observed;--actually only at low erythrocyte concentration (less than 10-11%) in microvessels. The results suggest that an increase in vascular resistance to blood flow must appear during a considerable slow-down of blood flow velocity in microvessels.

Animals↗

PubMed1995

Angiogenesis in colorectal tumors: microvessel quantitation in adenomas and carcinomas with clinicopathological correlations.

Angiogenesis is a crucial step in tumor growth and progression. Its quantitation by microvessel counting is of prognostic value in several types of malignancies. Scarce data are available on angiogenesis in gastrointestinal tumors. We studied 36 adenomas and 178 large bowel carcinomas to evaluate the onset of angiogenesis in colorectal tumorigenesis and to assess the prognostic significance of microvessel quantitation. Endothelial cells were immunostained with an anti-CD31 mAb; in each case three microscopic fields (x 200) with the highest number of microvessels were counted: the average value of the three fields was used to evaluate the significance of microvessel density (MVD). MVD of normal mucosa (41 cases) served as controls. MVD was 42 +/- 10 in the normal mucosa, 64 +/- 10 in adenomas, and 115 +/- 39 in carcinomas (normal versus adenomas, P < 0.001; adenomas versus carcinomas, P < 0.0001). The transitional mucosa adjacent to carcinomas displayed intermediate levels of MVD (89 +/- 23; P < 0.001 versus adenomas; P < 0.001 versus carcinomas). High MVDs were not associated with metastases, disease stage, and patient survival. The data indicate that angiogenesis is an early, critical step in colorectal tumorigenesis. MVD, however, does not provide significant prognostic information in colorectal cancer patients.

Adenocarcinoma↗

PubMed1994

Brain microvessels: factors altering their patency after the occlusion of a middle cerebral artery (Wistar rat).

The progression from ischemic injury to pannecrosis that occurs in the rat brain several hours after occluding a large artery may be partly attributable to a worsening of the circulation through the microvessels. The objective of this study was to quantitate selected structural changes involving astrocytes and endothelial cells within an area of focal brain ischemia created by the occlusion of a middle cerebral artery. The magnitude of these structural changes was correlated with alterations in the patency to a circulating macromolecule through the microvessels (< or = 15 mu in diameter) located within the territory of the occluded artery. One hundred eighty-five adult male Wistar rats had the right middle cerebral artery occluded after threading a nylon monofilament through the external carotid artery. Experiments were terminated by either cardiovascular perfusion or decapitation and immersion fixation at intervals ranging between 30 minutes and 7 days after the arterial occlusion. Randomly selected animals from each experimental subgroup were injected intravenously with horseradish peroxidase (molecular weight 44 kd) approximately 20 minutes before death. The progressive decline in the area fraction comprised by the vessels filled with horseradish peroxidase was preceded at 30 to 60 minutes by an increase in the surface area occupied (on a cross-section of a microvessel) by endothelial cells (both nucleus and cytoplasm). This was followed by an increase of 23.7% in the mean diameter of astrocytes nuclei and a decrease of approximately 35% in lumenal surface of the microvessels. These observations suggest that the occlusion of a large cerebral artery causes prompt swelling of endothelial cells and astrocytes; both of these early biological responses may interfere with erythrocyte circulation and oxygen delivery, which (after the arterial occlusion) are entirely dependent on the circulation provided by the collateral arterial connections. Through its interference with microvascular patency and oxygen delivery, cell swelling may influence the rate at which neurons become necrotic. In this model of brain infarct the number of necrotic neurons peaks approximately 72 hours after middle cerebral artery occlusion.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMedDate not supplied

Testicular intravascular volume and microvessel mitotic activity: effect of experimental varicocele.

Testicular blood flow increases bilaterally in animals with experimental left varicocele (ELV). The present experiments were undertaken to determine if increases in testicular intravascular volume and capillary growth were potential contributors to this increase in flow. Testicular intravascular volume (microliters/g) was estimated by determining testicular vascular 125I-albumin space. Microvessel mitotic activity was estimated by examining 3H-thymidine incorporation into endothelial nuclei, as assayed by silver grain localization over microvessel endothelial nuclei after exposure of testes to 3H-thymidine in vivo. Testicular intravascular volume was 25-30 microliters/g testis in control testes and in ELV animals was increased an average of 9% and 28% in right and left testes, respectively. This increase was statistically significant (P < 0.05) on the left side only. Approximately 1.5-2.0% of testicular microvessel endothelial nuclei exhibited silver grain localization, and ELV was not associated with a change in these values in either right or left testis. Ancillarily, there was a modest but significant association between microvessel mitotic activity and mitotic activity in adjacent seminiferous tubules. It was concluded that bilateral increases in testicular blood flow after ELV are not uniquely the result of bilateral expansion of intravascular volume and growth of the testicular capillaries. It is speculated, however, that mitogenic factors from the seminiferous tubules potentially affect mitotic activity of the adjacent microvasculature.

Animals↗

PubMed1996

Direct stimulation of limbal microvessel endothelial cell proliferation and capillary formation in vitro by a corneal-derived eicosanoid.

12(R)-Hydroxyeicosatrienoic acid (12(R)-HETrE), a corneal epithelial derived inflammatory eicosanoid, elicits blood vessel growth into the avascular cornea in the classical corneal micropocket bioassay. Using an in vivo stimulated angiogenesis assay and 12(R)-HETrE as the angiogenic stimulus, we isolated a homogeneous population of rabbit limbal microvessel endothelial cells, the target for angiogenic factors in the anterior surface of ocular tissues, and analyzed the mitogenic and angiogenic potential of this eicosanoid. 12(R)-HETrE stereospecifically increased cell number by approximately 45%, an effect comparable to that of basic fibroblast growth factor (0.6 nmol/L; 10 ng/ml). This potent mitogenic response was maximal at 0.1 nmol/L. An additive effect (approximately 90% above control) on cell proliferation was observed when 12(R)-HETrE (0.1 nmol/L) and basic fibroblast growth factor (0.6 nmol/L) were added to quiescent cultures of rabbit limbal microvessel endothelial cells. We also show that 12(R)-HETrE, but not 12(S)-HETrE, induces cultured rabbit limbal microvessel endothelial cells to organize themselves as a network of branching cords reminiscent of capillaries. This effect was evident within 48 hours, maximal by 5 days of culture, and paralleled the effect observed with basic fibroblast growth factor. This study describes a novel method for testing site-directed angiogenesis in vitro and further strengthens the angiogenic properties of 12(R)-HETrE by demonstrating a direct effect on limbal microvessel endothelial cells.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗

PubMed1996

Microvessel count predicts survival in uveal melanoma.

Microvessel density has become established as an important prognostic indicator for many tumor types. This study investigates the microvessel density as a prognostic factor for survival in patients with uveal melanoma, which is the commonest intraocular tumor and has a clear tendency for metastatic spread to the liver. Factor VIII-related antigen was identified immunohistochemically in bleached sections from 123 tumors. Maximum blood vessel density in an area of 0.25 mm2 was recorded, along with other accepted prognostic information. Microvessel density was the single most important prognostic factor on univariate testing, and in a Cox proportional hazard model, tumor size was the only other variable to be entered. No other accepted prognostic factor entered the model. We conclude that microvessel density is an important prognostic factor for survival in patients with uveal melanoma and allows the identification of high-risk patients for whom adjuvant therapy should be considered.

Biomarkers, Tumor↗

PubMed1996

Ontogeny of four blood-brain barrier markers: an immunocytochemical comparison of pial and cerebral cortical microvessels.

Pial and cortical microvessels possess many blood-brain barrier (BBB) properties in common, including impermeability to electron dense tracers, high transendothelial electrical resistance and specialised endothelial cell ultrastructural features. To compare pial and cortical microvessels further, a developmental, immunocytochemical study was undertaken of 4 BBB markers in the rat: OX-47, EBA, GLUT-1 and s-laminin. The appearance of the markers was monitored from embryonic d 16, to postnatal and adult stages. Each of the 4 markers appeared simultaneously in both pial and cortical vessels. GLUT-1 and OX-47 were present in endothelial cells of the BBB from E 16 to the adult. EBA and s-laminin appeared from postnatal d 7 through to the adult. Pial microvessels lack the ensheathment of astrocytes which may be involved in the induction and/or maintenance of BBB markers in the cortex. It is possible that astrocyte-derived factors diffusing from the brain surface are responsible for induction of BBB properties in the pial microvessels.

Animals↗

PubMed1997

Angiogenesis of uterine cervical carcinoma: characterization by pharmacokinetic magnetic resonance parameters and histological microvessel density with correlation to lymphatic involvement.

Dynamic studies of Gd-based contrast agents in magnetic resonance imaging (MRI) are increasingly being used for tumor characterization as well as therapy response monitoring. Because detailed knowledge regarding the pathophysiological properties, which in turn are responsible for differences in contrast enhancement, remains fairly undetermined, it was the aim of this project to: (a) examine the relationship between contrast-enhanced dynamic MRI-derived characteristics and histological microvessel density counts, a recognized surrogate of tumor angiogenesis, from primary or recurrent cancers of the uterine cervix; and (b) correlate these parameters with lymphatic involvement to characterize tumor aggressiveness in terms of lymphatic spread. Pharmacokinetic parameters (amplitude, A; exchange rate constant, k21) were calculated from a contrast-enhanced dynamic MRI series in 55 patients (ages 25-72 years; mean, 50 years) with biopsy-proven primary (n = 42) or recurrent (n = 13) uterine cervical cancer. Both pharmacokinetic parameters were correlated to histologically determined microvessel density counts (factor VIII-related antigen) and other pathological tumor characteristics obtained from the operative specimens after radical surgery. In addition, the magnetic resonance and histological data were correlated to the presence or absence of lymphatic system involvement. Pharmacokinetic MRI-derived parameters (A and k21) increased with increasing histological microvessel density counts with r = 0.41 and 0.50, respectively. Lymphatic involvement was more comprehensibly assessed by the pharmacokinetic parameter k21 compared with histological microvessel density, resulting in a higher sensitivity, overall accuracy, and comparable specificity. Contrast-enhanced MRI parameters might prove to be applicable for estimation of tumor angiogenesis in uterine cervical cancer; thus, MRI may become an additional tool to characterize malignant progression in terms of lymphatic involvement in uterine cervical cancer.

Adenocarcinoma↗