bluuebunny/crossref_metadata_2025_split huggingface dataset:
Influence of Microvascular Architecture on Oxygen Exchange in Skeletal Muscle
Authors: Pittman Roland N. 
Published: April 2008

ABSTRACTThe normal function of skeletal muscle requires that a continuous supply of oxygen be provided by the cardiovascular system. This article reviews the development of our understanding of the role of microvascular architecture on the oxygen transport system, with emphasis on direct microcirculatory observations and mathematical modeling dating from the work of August Krogh to present studies. The contributions of the various elements of the vascular network (i.e., arterioles, capillaries, and venules) and microvascular hemodynamics to oxygen exchange are discussed. Oxygen moves through the microvascular network by convection, almost all of it being reversibly bound to the hemoglobin within red blood cells. Thus, the flow properties and distribution of the red cells within the network can play a significant role in oxygen transport. Because the walls of all the vessels in the microcirculation appear to be permeable to oxygen, it continuously diffuses between the blood and the interstitium, the direction depending on the oxygen partial pressure difference. Because of the high permeability of the vascular wall to oxygen, the complex spatial relationships among the various microvessels lead to correspondingly complex diffusive interactions among them. The proximity of capillaries, arterioles, and venules, along with the anastomotic connections and tortuosity of capillaries, provides the “complex spatial relationships” that lead to diffusive interactions between neighboring capillaries, between capillaries and nearby arterioles and venules, and between paired arterioles and venules. Although there are a number of outstanding problems regarding our understanding of oxygen transport at the microcirculatory level, the most interesting and significant of these has to do with the adjustments that are made in the transition from the resting state to that of sustained aerobic exercise.
Estimation of In Vivo Pulmonary Microvascular and Interstitial Geometry Using Digital Image Analysis
Authors: VENTUROLI DANIELE , CRISAFULLI BEATRICE , DEL FABBRO MASSIMO , NEGRINI DANIELA , MISEROCCHI GIUSEPPE 
Published: April 2008

ABSTRACTObjective: To determine microvascular diameter and perivascular interstitium thickness at the lung surface in the in situ, in vivo lung.Methods: Microscopic images of the lung surface collected through a “pleural window” by a videocamera were digitized with a monochrome frame grabber (512 × 512 pixels, 8 bits per pixels) to be computer analyzed by image processing techniques.Results: We found that the maxima in the distribution of the standard deviations of gray levels in adjacent neighbors 7 × 7 pixels wide identify the edges between the microvessel lumen and the surrounding perivascular interstitium. Furthermore, the maxima in the distribution of the standard deviation of the standard deviations of gray levels identify the edges between the perivascular interstitium and the lung tissue.Conclusions: This technique can be applied to microvessels ranging in diameter from 30 μm to 200 μm and perivascular interstitial thickness of the order of 10–150 μm. Our approach allows for the definition of microvascular geometry even for noisy images and represents an improvement compared to other edge detection methods. The proposed analytical procedure may provide a useful tool to study lung fluid balance and microvascular reactivity in the in situ lung in the normal state and in response to a variety of functional conditions.
Renal Medullary Microcirculation: Architecture and Exchange
Authors: MICHEL C. C. 
Published: April 2008

ABSTRACTThe architecture of the renal medullary microcirculation is highly specialized. Consistent with their role in countercurrent exchange, the vessels (the vasa recta and the intervening capillaries) have high permeabilities to fluid and small hydrophilic solutes. The urea permeability of the continuous endothelium of the descending vasa recta (DVR) in the outer medulla is greatly enhanced by a urea transporter. Aquaporin channels have also been identified in these vessels. In spite of the absence of lymphatics from the inner medulla, fluid uptake from the interstitial fluid (ISF) through the fenestrated endothelium of the ascending vasa recta (AVR) appears to be driven by differences in hydrostatic and oncotic pressure. Because the AVR have high Lp's [10−5 cm s−1 (cm H2O)−1] and are mechanically linked to surrounding structures, small increments of ISF pressures above the pressure within the AVR can drive significant volumes of fluid into AVR if ISF volume expands. The lower reflection coefficients to serum albumin of the AVR as compared with the DVR may be important in the clearance of interstitial plasma protein. Recent work on isolated DVR from the outer medulla has revealed that these vessels are capable of vasoconstriction and thus of regulating medullary blood flow.
Thromboxane Contributes to Submaximal Coronary Dilation During Myocardial Ischemia
Authors: ELLER BRIAN T. , BROOKS LEONARD A. , DELLSPERGER KEVIN C. 
Published: April 2008

ABSTRACTObjectives: Thromboxane has been shown to contribute to coronary constriction in conduit coronary arteries during platelet aggregation at the site of a critical stenosis. Previous studies from our laboratory suggest that following a critical coronary stenosis, persistent vasomotor tone occurs. We tested the hypothesis that thromboxane is responsible for that increased tone.Methods: To test this hypothesis, 14 mongrel dogs of either sex were anesthetized and subjected to a critical coronary stenosis where distal coronary perfusion pressure was reduced to 36 ± 2 mm Hg. During the coronary stenosis, SQ 29,548 (thromboxane/endoperoxide receptor antagonist) was administered intravenously (0.2 mg/kg and 2.0 mg/kg). Coronary microvascular responses were observed by directly visualizing the epicardial microcirculation. Diameters were measured using intravital microscopy coupled to stroboscopic epi‐illumination and jet ventilation to compensate for cardiac and respiratory‐induced motion.Results: Coronary microvessels were divided into small (< 150 μm) and large (> 150 μm) arterioles. During SQ 29,548 administration, small coronary arterioles demonstrated no additional dilation during a critical coronary stenosis. In contrast, coronary microvessels > 150 μm demonstrated a dose‐dependent vasodilation to SQ 29,548 (0.2 mg/kg: 6 ± 2%; 2.0 mg/kg: 11 ± 4%; P < 0.05 vs. no change). A time control study in six additional animals demonstrated no significant coronary microvascular diameter changes following a critical stenosis over the time course of SQ 29,548 administration.Conclusion: Endoperoxides contribute to poststenotic microvascular vasoconstriction in vessels 150–300 μm.
Nitric Oxide Affects Microvascular Permeability in the Intact and Inflamed Vasculature
Authors: Kubes Paul 
Published: April 2008

ABSTRACTThere is a growing body of evidence that nitric oxide modulates the movement of fluid and protein out of the vasculature. However, the results obtained from whole organ, single vessel, and endothelial monolayer studies are often not consistent. In fact, there is much evidence that endogenous nitric oxide increases microvascular permeability and equally compelling evidence to suggest that endogenous nitric oxide decreases microvascular permeability. In this review we summarize and critically evaluate the data published to date regarding the role of nitric oxide as a modulator of microvascular permeability under both normal conditions and following exposure to various stimuli. The last section of the chapter discusses the importance of nitric oxide as a modulator of microvascular permeability in inflammatory conditions. Particular emphasis is placed on the stimuli used, the organ systems studied, and the measurements performed to investigate the effects of nitric oxide on microvascular permeability alterations.
Type II Collagen Is a Major Component of Bovine Retinal Microvessel Extracellular Matrix
Authors: SWINSCOE JOHN C. , CARLSON EDWARD C. 
Published: April 2008

ABSTRACTObjective: To determine which interstitial collagen types may be present in bovine retinal microvessel extracellular matrix (ECM).Methods: Dissociated bovine microvessels were treated with detergents and the resultant purified ECM monitored by transmission electron microscopy (TEM). Pepsin‐extracted soluble ECM collagens were identified by Western blots. Collagens were further purified by neutral salt precipitation and carboxymethyl cellulose (CMC) chromatography before cyanogen bromide (CNBr) peptide mapping and two‐dimensional peptide mapping of CMC‐generated fractions. Interstitial collagens were localized by immunofluorescence on frozen sections.Results: Transmission electron microscopy of detergent‐purified microvessel ECM demonstrated numerous 10–50‐nm collagen fibrils associated with basal laminae regardless of vessel diameter. Western blots showed that soluble ECM collagens were strongly positive for type II, moderate for type III, and weak for type I. CNBr peptide maps and two‐dimensional maps of neutral salt and CMC‐purified fractions confirmed the presence of type II collagen. Immunofluorescence localized type II collagen in large and small vessels of the retina.Conclusions: Type II collagen is an unexpected major component of bovine microvessel ECM, whereas types I and III are present in minor amounts. Type V collagen is also a substantial ECM component. Accordingly, all four types may contribute to a heterogeneous population of collagenous fibrils identified by TEM in intact isolated retinal microvessel ECM.
Visualization of Endothelial Clefts and Nuclei in Living Microvessels with Combined Reflectance and Fluorescence Confocal Microscopy
Authors: He P. , Adamson R. H. 
Published: April 2008

ABSTRACTObjective: The cellular basis for spatial heterogeneity along postcapillary venules in their response to inflammatory mediators is not understood. To study permeability regulatory processes on an individual cell basis in intact microvessels, we developed methods to delineate individual endothelial cells within living, single perfused microvessels.Methods: Individual postcapillary microvessels in the mesenteries of frogs and hamsters were perfused with chloride‐free Ringer's solutions containing AgNO3 (0.1 g per 100 ml) for 5–10 s. Vessels were immediately flushed with Ringer's solution containing serum albumin and some vessels subsequently perfused with the fluorescent nucleic acid stain YO‐PR0‐1 (1 μM) for 10–15 min. Vessels were imaged in situ using laser scanning confocal microscopy. A reflectance image from silver precipitate in the endothelial clefts and a fluorescence image of the nuclei were simultaneously recorded. Stacks of confocal images were merged and used to reconstruct the three‐dimensional orientation of endothelial cells. Hydraulic conductivity of some frog mesenteric venular vessels, measured before and after perfusion with AgNO3, was used to assess the integrity of the vessels.Results: The endothelial cell clefts were delineated with a very fine, readily imaged precipitate of silver. Hydraulic conductivity measured after AgNO3 perfusion in frog mesenteric venular microvessels was not significantly different from control. Vessels showed a slight reduction in reactivity to inflammatory stimuli. The three‐dimensional pattern of endothelial cells in the living vessels was imaged.Conclusions: Combining confocal microscopy with silver staining in single perfused microvessels was shown to be an effective means to delineate the three‐dimensional pattern of endothelial cells forming microvessel walls. It enables further study of the vascular structure and function relationships at the individual cell level in intact microvessels.
Putrescine: A Novel Inhibitor of Glycosylation‐Induced Cross‐Links in Laniinin
Authors: TSOPANOGLOU NICOS E. , ZIOUDROU CHRISTINE , TSILIBARY EFFIE C. , CHARONIS ARISTIDIS S. 
Published: April 2008

ABSTRACTObjective: To determine whether putrescine, a naturally occuring polyamine, is able to prevent nonenzymatic glycosylation‐induced cross‐linking of basement membrane components. Cross‐linking, leading to the formation of advanced glycosylation end products (AGEs) has been proposed as a major mechanism contributing to structural and functional changes of the vascular wall, thus leading to microangiopathy.Methods: Laminin, a major basement membrane glycoprotein present in the microvasculature, was isolated and incubated in the presence of high glucose concentrations, in order to generate an in vitro diabetic environment. Putrescine was either present or absent from the incubation mixture. Formation of cross‐links was assessed by two independent methods: gel electrophoresis and development of characteristic fluorescence.Results: Putrescine inhibited in a dose‐dependent manner the formation of slower mobility bands in gel electrophoresis. Quantitation of the development of fluorescence characteristic of glycosylation‐induced cross‐links demonstrated that putrescine inhibited the formation of fluorescent products.Conclusions: Putrescine may be a promising compound for inhibition of protein cross‐linking and, therefore, could be used in the prevention of diabetic microangiopathy.
The Tracheobronchial Vasculature: A Possible Role in Asthma
Authors: Widdicombe John 
Published: April 2008

ABSTRACTThe tracheobronchial microcirculation consists of a subepithelial capillary network and in some species deeper capacitance vessels and an adventitial network. Postcapillary venules are the main site of plasma extravasation in inflammatory conditions. There are surprising species differences. The subepithelial capillary network is dense in species such as sheep and dog but relatively scanty in rabbit and humans. Sheep have conspicuous capacitance vessels or blood sinuses, especially in the trachea and at points of bronchial branching with walls that lack smooth muscle. The rabbit also has a well‐developed capacitance system but the blood sinuses have thick muscular walls. Although the capacitance system in humans has not been studied much it is probably present with muscular walls. It is absent in rats but present in guinea pigs. Thus, in some species the tracheobronchial vasculature may give the mucosa an erectile capacity, as in the nose of each species. Arteriovenous anastomoses (AVA) cannot be demonstrated physiologically in sheep but they seem to be present as thoroughfare vessels in rats and guinea pigs. Whether they exist in humans is not known. The absence of AVA might indicate a weak or absent thermoregulatory and air conditioning role for the lower airway vasculature.Extensive studies of neurogenic inflammation in rodents show that sensory neuropeptides can open gaps between the endothelial cells of postcapillary venules and the same change can be caused by a large number of inflammatory mediators. These opened gaps cause extravasation of plasma into the interstitium. Small increases in interstitial pressure lead to spaces opening between the epithelial cells and exudation of plasma into the airway lumen.The role of the airway microvasculature in asthma is controversial. Cold and hyperosmolar solutions cause vasodilatation as do the mediators released in the mucosal inflammation of asthma. However, quantitation of the thickening of the airway wall due to vascular engorgement, mucosal edema, or increased luminal liquid does not prove that these changes are a cause of airway obstruction. The contraction of airway smooth muscle superimposed on the mucosal inflammatory pathology might lead to a synergistic mechanism to increase airway resistance.
Presented at the 1995 Microcirculatory Society Meeting
Authors: Hoying James B. , Williams Stuart K. 
Published: April 2008

ABSTRACTObjective: The under‐agarose migration assay developed for use with endothelial cells provides a measurement of the intrinsic migratory behavior of a cell population. However, the assay is labor intensive and lacks experimental flexibility. This migration assay has been refined and tested on human microvessel endothelial cells in the presence of a migration stimulus or on differing matrix‐coated substrates.Methods: The improved assay retains the linear geometry and mathematical basis of the under‐agarose assay. Cells migrating from a cell reservoir formed with a Delrin® insert are counted using an automated image‐analysis system utilizing a high‐contrast, fluorescent nuclear stain. From the cell counts, a stochastic measure of random migration is calculated.Results: Values for random migration between the improved migration assay and the traditional under‐agarose assay were very similar. Furthermore, a stochastic measure of endothelial cell migration on fibronectin was determined.Conclusions: This improved linear migration assay permits readily obtainable measures of endothelial cell migration for a number of experimental conditions. Improvements in the assay include the use of a removable fence for forming cell reservoirs, a nuclear stain to facilitate cell counting, and a more comprehensive analysis of the cell migration.
Relationship Between Fiber Capillarization and Mitochondrial Volume Density in Control and Trained Rat Soleus and Plantaris Muscles
Authors: Poole David B. , Mathieu‐costello Odile 
Published: April 2008

ABSTRACTObjective: The majority of investigations have demonstrated a strong relationship between muscle capillarity and oxidative capacity. There is, however, evidence that die capacities for O2 supply and utilization can be dissociated. Also, metabolite removal rather man O2 supply may represent the predominant design constraint placed on the capillary bed in some muscles (i.e., fast‐twitch glycolytic). Recent evidence suggests mat the principal barrier to O2 diffusion in skeletal muscle resides between the red blood cell and the immediately subjacent sarcolemmal space. Consequendy, if the primary design constraint placed on the capillary bed is to facilitate O2 exchange, we hypothesized that capillary surface per fiber surface should be correlated with die mitochondrial volume subserved. Thus, the purpose of this study was to investigate whether one single relationship would be found between the capillary‐to‐fiber surface ratio and fiber mitochondrial volume in slow‐ (soleus) and fast‐twitch (plantaris) muscle and whether this relationship would be preserved after training.Methods: Rats were exercise‐trained on a motor‐driven treadmill up to 60 min/day, 5 days/week for 4 weeks at an intensity calculated to elicit V 75% VO2max. Following training, soleus (S) and plantaris (P) muscles were removed under deep anesthesia for citrate synthase analysis, and the contralateral limb was perfusion‐fixed in situ with glutaraldehyde and analyzed morphometrically under light and electron microscopy.Results: Training significantly (p < 0.05) increased citrate synthase activity and capillary‐to‐fiber ratio both in S and P muscles. For all muscles combined (i.e., S and P, control and trained), the capillary‐to‐fiber surface ratio significantly correlated with mitochondrial volume per unit fiber length (r = 0.64).Conclusions: Our finding of a single relationship between the capillary‐to‐fiber surface ratio and fiber mitochondrial volume across the muscles is consistent with the notion that the size of the capillary bed in muscles comprised principally of either slow‐twitch oxidative or mixed fast‐twitch oxidative glycolytic and fast‐twitch glycolytic fibers is primarily designed to meet fiber requirements for O2 exchange, and that an important site for O2 diffusion resistance is at the capillary‐fiber interface. In addition, capillary‐to‐fiber surface and fiber mitochondrial volume increased in similar proportions, i.e., the relationship between the two variables was preserved after endurance training.
Dietary Myo‐inositol Restores Diabetic Renal Arteriolar Reactivity to Angiotensin II but not to Norepinephrine
Authors: Inman S. R. , Porter J. P. , Fleming J. T. 
Published: April 2008

ABSTRACTObjective: This study addresses the hypothesis that the diminished constriction of renal arterioles to angiotensin II (Ang II) and norepinephrine (NE) in diabetic rats is due to elevated activity in the polyol pathway. This activity results in reduced incorporation of myo‐inositol into membrane phospholipids and impaired signal transduction.Methods: The left ureter of female Wistar rats (140‐160 g) was surgically ligated. Four to six weeks later, streptozotocin (50 mg/kg, i.p.) was injected in half of the rats to induce diabetes. Beginning on the day of streptozotocin injection, diabetic and nondiabetic rats were fed either a standard diet or a diet enriched with 1% myo‐inositol. Seven to 10 days later, all rats were anesthetized and the hydrone‐phrotic kidney was bisected and exteriorized in a bath for direct visualization of the renal microvasculature. The constrictor responses of interlobular, afferent, and efferent arterioles to Ang II or NE (applied to the bath) were directly quantitated by in vivo microscopy.Results: Among diabetic rats, the myo‐inositol‐enriched diet significantly enhanced the constriction of interlobular, afferent, and efferent arterioles in response to Ang II, so that the responses to the peptide were almost completely restored to normal. Constriction to NE by interlobular arteries and afferent arterioles (but not efferent arterioles) was also significantly attenuated among diabetic rats fed the standard diet. However, unlike what was observed for Ang II, the myo‐inositol‐enriched diet did not enhance constriction to NE among diabetic rats.Conclusions: These data indicate that different mechanisms are responsible for decreased renal arteriolar constriction due to Ang II and NE in early diabetes. Diminished arteriolar constriction due to Ang II, but not to NE, may be linked to altered myo‐inositol metabolism.
Lymphatic Microcirculation
Authors: Zawieja David C. 
Published: April 2008

ABSTRACTObjective: The importance of the lymphatic system during inflammatory response is underscored by the discovery that numerous inflammatory mediators alter the lymph pump. Inhibition of the lymph pump will reduce the lymphatic outflow from the interstitial space and thus initiate the lymphatic generation of edema. We evaluated the effect that reactive oxygen metabolites have on the contractile activity of lymphatic vessels.Methods: Reactive oxygen metabolites are produced during inflammation and have been implicated in a number of pathologies. Exposure to reactive oxygen metabolites inhibited the lymph pump flow in a time‐ and concentration‐dependent fashion by decreasing contraction frequency, strength, and propagation.Results: Substance P (SP) (1.0 μM) produced the following changes (% control): reductions in diastolic diameter (56%), systolic diameter (47%), and stroke volume of the lymph pump (62%); a large increase in lymphatic contraction frequency (640%); and a modest increase in lymph pump flow (43%). SP also stimulated quiescent vessels to develop typical contraction‐relaxation patterns. These effects may serve to minimize the formation of edema in the face of inflammatory edemagenic conditions that are produced by SP.Conclusions: We concluded that reactive oxygen metabolites significantly inhibit the active lymph pump and that this inhibition could be an important contributing factor in the formation of interstitial edema during inflammation. We have also determined the effects of a putative mediator of inflammation (SP) on the lymphatic pumping function.