bluuebunny/crossref_metadata_2025 huggingface dataset:
The Tracheobronchial Vasculature: A Possible Role in Asthma
Authors: Widdicombe John
Published: April 2008

The 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

Objective: 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

Objective: 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

Objective: 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

Objective: 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.
Decreased Deformability of Polymorphonuclear Leukocytes in Diabetic Cats
Authors: Braun Rod D. , Fisher Timothy C. , Meiselman Herbert J. , Hatchell Diane L.
Published: April 2008

Objective: Polymorphonuclear leukocytes (PMN) have been found to be less deformable in humans with non‐insulin‐dependent diabetes. It has therefore been hypothesized that white blood cells (WBC) may affect the development of diabetic microangiopathy. This study was designed to determine whether PMN or small and large lymphocytes were less deformable in a large animal model of diabetes—chronically hyperglycemic pancreatectomized cats.

Methods: Venous blood was withdrawn from 13 normal and 14 diabetic cats. The diabetic cats had been kept in poor metabolic control since their pancreatectomy (7‐113 months before this study). Blood cell counts, hemoglobin concentration, hematocrit, erythrocyte volume, and WBC differential counts were obtained from the blood samples. Purified mononuclear WBC and PMN fractions were obtained by separating the blood on a discontinuous Percoll gradient. The deformability of each cell fraction was determined using a Cell Transit Analyzer (ABX, Montpellier, France) that measures the transit time of cells through 7.5‐μm pores. By varying the sampling rate of the CTA and the pressure difference across the filter, the subpopulations of the mononuclear fractions (small and large lymphocytes) could be identified and each subpopulation analyzed separately.

Results: Median transit times for the PMN and small lymphocytes were significantly greater for the diabetic cats, but no difference was found in the large lymphocyte fractions.

Conclusions: These results are in accordance with the finding that PMN are less deformable in humans with diabetes. We also showed that the small lymphocytes from diabetic cats have prolonged transit times. The results suggest that PMN may contribute to the development of microangiopathies like diabetic retinopathy. Diabetic cats may prove useful for testing potential therapies to improve WBC deformability.
Apigenin Inhibits Tumor Necrosis Factor‐Induced Intercellular Adhesion Molecule‐1 Upregulation In Vivo
Authors: Panés Julián , Gerritsen Mary E. , Anderson Donald C. , Miyasaka Masayuki , Granger D. Neil
Published: April 2008

Objective: Apigenin is a flavonoid that effectively blocks intercellular adhesion molecule‐1 (ICAM‐1) upregulation and leukocyte adhesion in response to cytokines in vitro. In the present study, we characterized the effects of tumor necrosis factor (TNF) on ICAM‐1 expression in different tissues of the rat. We then assessed whether apigenin alters this response.

Methods: ICAM‐1 expression was measured under baseline conditions or 5 h after treatment with rTNF. We used 125I‐labeled anti‐rat ICAM‐1 monoclonal antibody (mAb) and an isotype‐matched control mAb labeled with 131I to correct for nonspecific accumulation of the binding mAb. Animals were pretreated with either placebo, apigenin, narigenin (a flavonoid without inhibitory effect in vitro), or vehicle. Additional groups of animals were treated with either allopurinol, glutathione, dimethyl‐thiourea, or an anti‐CD18 monoclonal antibody in order to assess possible actions of flavonoids that were mediated via free radical scavenging or through interference with neutrophil function.

Results: Treatment with rTNF resulted in a marked increase in ICAM‐1 expression in all organs studied. The magnitude of the response varied in different organs and increases ranged from onefold (lung) to threefold (muscle). Treatment with apigenin blocked ICAM‐1 upregulation in organs with low to intermediate responses to rTNF and it significantly attenuated the increased ICAM‐1 expression in organs that normally exhibit more marked upregulation. Treatment with narigenin or vehicle did not affect rTNF‐induced ICAM‐1 upregulation in all tissues studied. Pretreat‐ment with either allopurinol, free radical scavengers, or anti‐CD18 monoclonal antibody did not affect the ICAM‐1 upregulatory response to rTNF.

Conclusions: TNF‐induced ICAM‐1 upregulation in vivo effectively is blocked by apigenin through a mechanism that is unrelated to free radical scavenging or leukocyte function.
Intravital Microscopy of the Peripheral Lymph Node Microcirculation in Mice
Authors: Von Andrian Ulrich H.
Published: April 2008

Objective: The purpose of this study was to develop a model for microscopic in situ observation of the murine peripheral lymph node (LN) microcirculation and to characterize the function of the lymphocyte homing receptor L‐selectin (CD62L) and the peripheral node addressin (PNAd). The latter is a high‐affinity ligand for L‐selectin in LN high endothelial venules (HEV).

Methods: The subiliac (superficial inguinal) LN was microsurgically dissected in anesthetized adult mice. The nodal microvascular architecture and venular hemodynamics were characterized by bright field and epifluorescence video microscopy. L1‐2 pre‐B cells that were either mock transfected (L1‐2Vector) or stably transfected to express human L‐selectin (L1‐2L‐selection) were labeled fluorescently and injected into a feeding artery. Cell adhesion in LN venules was studied in both the presence and absence of neutralizing monoclonal antibodies (MAb) to PNAd and L‐selectin.

Results: The preparation allowed a detailed analysis of hemodynamic parameters and leukocyte adhesion in LN microvessels. L1‐2Vector cells did not interact with LN microvessels. In contrast, L1‐2L‐selectin cells rolled efficiently in venules but not in arterioles or capillaries. Rolling was most prominent in subcortical HEV (orders III to V) and was less frequent but consistently detectable in downstream medullary and hilus venules (orders I and II). Rolling interactions were abrogated by MAb DREG‐56 to the lectin domain of L‐selectin and were markedly reduced by the anti‐PNAd MAb MECA‐79.

Conclusions: The present study develops a new intravital microscopy model for in vivo visualization of leukocyte interactions with microvessels in murine LN. The preparation permitted an analysis of biophysical and molecular mechanisms of leukocyte adhesion to high endothelial cells. The data support the concept that L‐selectin and PNAd are the predominant receptor/ligand pair responsible for lymphocyte rolling in HEV. The model will be useful for high‐resolution analysis of intra‐ and extravascular events in living LN.
Neutrophil‐Endothelial Interactions in a Cell‐Column Model of the Microvasculature: Effects of fMLP
Authors: Haselton F. R. , Woodall J. H. , Alexander J. S.
Published: April 2008

Objective: The purpose of this study was to develop an in vitro model which, compared to stagnant two‐chamber systems, is more analogous to the rheological conditions found in the vasculature and permits near simultaneous measurement of polymorphonuclear leukocytes (PMN) entrapment and endothelial monolayer permeability.

Methods: A previously described cell‐column model of the vasculature was perfused with 2 ± 106 PMN/ml at an average fluid velocity of 0.09 cm/s and an average estimated endothelial surface shear stress of 4.5 dyne/cm2 for a total of 60 min. PMN entrapment was estimated from counts of PMN in this recirculating system. Bovine endothelial permeability was estimated from an indicator dilution analysis of the three co‐injected dyes: blue dextran (molecular weight [MW]) 2 ± 106), sodium fluorescein (MW 342) and cyanocobalamin (MW 1355).

Results: Circulation of PMN through cell‐columns did not activate PMN, although the number of circulating PMN decreased at a rate of 14% per 65 cm2 of endothelial surface in the first 15 min. Endothelial cell monolayer permeability did not change within 60 min. Addition of formyl‐methionyl‐leucyl‐phenylalanine (fMLP) (lO−5 M) activated PMN and significandy increased entrapment of circulating PMN to 27% per 65 cm2 in the first 15 min. Although the percentage of circulating PMN entrapped increased, endothelial monolayer permeability was not increased by either the addition of 10−5M fMLP or PMN + fMLP to the cell‐column perfusate.

Conclusions: Over the 60‐min period studied, entrapment of PMN within a recirculating model of die microvasculature was not associated with an increase in endothelial permeability even after PMN stimulation with fMLP.
Cytokeratin Expression and Hyaluronic Acid Production in Cultures of Human Synovial Microvascular Endothelial Cells: Influence of Cytokines and Growth Factors
Authors: Carley William W. , Szczepanski Andrew , Gerritsen Mary E.
Published: April 2008

Objectives: To isolate and characterize human synovial endothelial cells and to determine the effects of cytokines and fibroblast growth factor on human synovial endothelial (HSE) cell hyaluronic acid production.

Methods: Endothelial cells were isolated from primary cultures of human synovial cells by fluorescent activated cell sorting based on the incorporation of a fluorescent derivative of acetylated low‐density lipoprotein (DiI‐Ac‐LDL). Identity of endothelial cells was confirmed by positive immunostaining for von Willebrand factor (vWf), cytokeratins, endoglin, and reactivity with the lectin ulex europeaus agglutinin (UEA). Hyaluronic acid production was measured by a radioligand‐binding assay.

Results: HSE cells were isolated and maintained in long‐term culture. The identity of the cultured cells as endothelial was based on uniform uptake of a (DiI‐Ac‐LDL), immunoreactivity for vWf, and endoglin and the binding of the lectin UEA. In addition, small blood vessels in the synovium were stained selectively with anticytokeratin antibodies K4.62 (cytokeratin 19 specific) and K8.13 (reactive for cytokines 1, 5, 6, 7, 8, 10, 11, and 18). Isolated HSE cells also demonstrated immunoreactivity with these cytokeratin antibodies. The cytokeratins identified by the monoclonal antibody clone K8.13 demonstrated a diffuse, fibrillar staining pattern. The cytokeratin distribution revealed with monoclonal antibody K4.62 (cytokeratin 19) was also fibrillar; however, the majority of cells also demonstrated numerous punctate cytoplasmic vesicular structures. Treatment of HSE cells with interleukin‐1α (IL‐1α) or acidic fibroblast growth factor (aFGF), but not tumor necrosis factor (TNFα), dramatically reduced the vesicular structures staining with the K4.62 antibody. HSE cells produced hyaluronic acid (HA) at a constitutive rate of 200–800 ng/105 cells/24 h, which could be upregulated when the cells were incubated with either IL‐1α or aFGF. HA production was not significantly increased when HSE cells were incubated with TNFα, IL‐4 or interferon‐γ.

Conclusions: Synovial microvascular endothelial cells produce and secrete HA and endothelial HA secretion is upregulated by IL‐1 and aFGF. IL‐1 and aFGF also reduce the number of vesicular‐like structures immunoreactive with a monoclonal antibody to cytokeratin 19. These studies suggest that cytokine stimulation of local endothelial secretion and/or accumulation of HA may influence leukocyte adhesion to the synovial endothelium.
Degranulation of Mast Cells in the Chick Chorioallantoic Membrane Does Not Increase Macromolecular Extravasation During Normal Angiogenesis
Authors: Rizzo Victor , Shumko John Z. , DeFouw David O.
Published: April 2008

Objective: To test the hypothesis that stimulation of mast cell degranulation during normal angiogenesis in the chick chorioallantoic membrane (CAM) serves to acutely activate macromolecular transendothelial pathways.

Methods: Using shell‐less cultures of 6‐day‐old chick embryos, efflux of fluorescein isothiocyanate (FITC)‐dextran 150 from CAM microvessels was evaluated, after applications of compound 48/80 or exogenous histamine, by computer‐assisted videodensitometric analyses. Real‐time confocal imaging enabled optical differentiation of first‐order pre‐ and postcapillaries from the capillary networks. Cytologic ultrastructure of the microvascular units was also evaluated.

Results: Although endogenous histamine was measurable and its concentration was increased after application of compound 48/80, segmental endothelia of the CAM microvascular units consistently restricted extravasation of FITC‐dextran 150. Furthermore, intravascular injections of histamine also failed to induce interendothelial gap formation or macromolecular flux across the segmental CAM endothelia.

Conclusions: These results are consistent with the interpretation that histamine‐activated transendothelial pathways are inactive in the CAM at day 6. Whether such inactivity serves to retard facilitation of CAM angiogenesis by activated mast cells remains to be tested.
Age‐Related Differences in Intestinal Arteriolar Responses to Venous Pressure Elevation in the Rat
Authors: Gosche John R. , Harris Patrick D. , Garrison R. Neal
Published: April 2008

Objective: We previously reported differences in intestinal arteriolar responses of adult and suckling rats to three stressors (hemorrhage, hypoxia, and hypothermia) that decreased intestinal blood flow. The small, premucosal arterioles of adult rats dilated in response to all three stressors, whereas the premucosal arterioles of suckling rats constricted or remained unchanged. One explanation for this difference might be absence of myogenic responsiveness in the premucosal arterioles of the immature rat.

Methods: We used in vivo videomicroscopy to observe the intestinal arteriolar responses to venous pressure elevation (a myogenic stimulus) in adult (8‐ to 12‐week‐old) and suckling (8‐ to 12‐day‐old) Sprague‐Dawley rats. We increased portal venous pressure by 25 and 50% above the baseline pressure.

Results: Arterioles in the adult rats displayed the expected “myogenic” response to venous pressure elevation (diameters decreased 12–19% when venous pressure was increased by 50%). In contrast to adult rats, arterioles in the suckling rats failed to constrict in response to increases in venous pressure (diameters increased 14–21% in response to a 50% increase in venous pressure).

Conclusions: These results suggest diat the myogenic constrictor mechanisms for control of the microcirculation appear to be either nonfunctional or suppressed in the intestinal microcirculation of suckling rats.
Blood Flow in the Cerebral Capillary Network: A Review Emphasizing Observations with Intravital Microscopy
Authors: Hudetz Antal G.
Published: April 2008

Capillary perfusion in the brain is characterized by an essentially continuous flow of erythrocytes and plasma in almost all capillaries. Rapid fluctuations and spatial heterogeneity or red blood cell (RBC) velocity (0.5–1.8 mm/s) within the capillary network are present. In addition, low‐frequency (4–8 cpm) synchronous oscillations in RBC velocity in the capillary network emerge when perfusion to cerebral tissue is challenged. Despite the tortuous, three‐dimensional architecture of microvessels, functional intercapillary anastomoses are absent. At rest, red cells travel through the capillary network in 100–300 ms along 150‐ to 500‐μm‐long paths. Physiological challenges elicit sizable changes in RBC velocity with a minor role for capillary recruitment, change in capillary diameter, or flow shunting. During acute hypoxia, RBC velocity increases in all capillaries; the corresponding response to hypercapnia is more complex and involves redistribution of capillary flow toward more homogeneous perfusion. The response of capillary flow to decreased perfusion pressure reflects autoregulation of cerebral blood flow but also involves intranetwork redistribution of RBC flow between two populations of capillaries, postulated as thoroughfare channels and exchange capillaries. Flow reserve may be provided by the thoroughfare channels and may help maintain flow velocity and capillary exchange and protect the microcirculation from perfusion failure. Isovolemic hemodilution increases RBC velocity three‐ to fourfold and increases RBC flux to a moderate degree with a relatively small decrease in capillary hematocrit, under normal and compromised arterial blood supply. In cerebral ischemia, leukocyte adhesion is enhanced and appears reversible when the ischemia is moderate but may be progressive when the injury is severe. The observed flow behavior suggests the presence of a physiological regulatory mechanism of cerebral capillary flow that may involve communication among various microvascular and parenchymal cells and utilize locally acting endothelial and parenchymal mediators such as endothelium‐derived relaxing factor or nitric oxide.
Femoral Artery Ligation Stimulates Capillary Growth and Limits Training‐Induced Increases in Oxidative Capacity In Rats
Authors: Roberts Karl C. , Nixon Craig , Unthank Joseph L. , Lash Julia M.
Published: April 2008

Objective: The purpose of this study was to assess the interaction of arterial insufficiency and exercise training on soleus and plantaris muscle capillarity and oxidative capacity in adult rats.

Methods: Arterial insufficiency was created by ligation (LIG) of the right femoral artery, and exercise training (TR) was performed on a rodent treadmill. The left hindlimb served as a normally (NORM) perfused control. Capillary:fiber ratio, number of capillary contacts per fiber, and citrate synthase activity (CS) were evaluated in the plantaris (Plant) and soleus (Sol) muscles.

Results: In sedentary rats, CS was similar between LIG and NORM (Plant: 24.4 vs. 24.3 μmol · min−1 · g−1; Sol: 16.6 vs. 16.9 μmol · min−1 · g−1), but capillaries per fiber and capillary contacts per fiber were significantly elevated in the plantaris muscle of LIG (2.46 vs. 2.10 caps/fiber, 5.78 vs. 5.03 capillary contacts). CS was elevated in both limbs of TR but was lower in LIG than in NORM (Plant: 28.5 vs. 32.4 μmol · min−1; · g−1; Sol: 21.1 vs. 24.9 μmol · min−1 · g−1). Treadmill training did not significantly affect capillarity in NORM. However, muscles in the ligated limb of TR tended to have greater capillarity than comparable muscles in either NORM of TR of LIG in SED.

Conclusions: These results demonstrate capillary proliferation in the plantaris but not soleus muscle of rat hindlimbs with femoral artery ligation. Capillarity and CS adaptations were not obligatorily related in LIG, and femoral artery ligation and exercise training appeared to have interactive effects on skeletal muscle capillarity.
Arteriolar Dilation Produced by Venule Endothelium‐Derived Nitric Oxide
Authors: Falcone Jeff C. , Meininger Gerald A.
Published: April 2008

Objective: We conducted bioassay experiments to determine whether nitric oxide produced by endothelial cells (endothelial‐derived nitric oxide, or EDNO) within large venules could act to dilate arterioles.

Methods: In these experiments, parallel segments of first‐order arterioles and venules were isolated from skeletal muscle and were cannulated in series with a glass connecting tube (length: 300–500 μm). Arterioles were mechanically denuded of endothelium by a delicate yet abrasive rubbing technique. Venular endothelium remained intact. Endothelial denudation of arterioles was confirmed by the absence of dilation during exposure to acetylcholine (10−6 mol/L). The cannulated vessels were pressurized to 30 cm H2O and the arterioles preconstricted by approximately 50% with norepinephrine (10−10 mol/L).

Results: Topical applications of acetylcholine (10−6 mol/L) or bradykinin (10−9 mol/L) during luminal perfusion from venule to arteriole produced significant arteriolar dilation. In contrast, a slight arteriolar constriction was observed when the direction of flow was reversed (i.e., arteriole to venule) in the presence of either acetylcholine (10−6 mol/L) or bradykinin (10−9 mol/L). Inhibition of venular EDNO with; NC‐monomethyl‐L‐arginine (L‐NMMA; 10−5 mol/L; 1 hour) completely abolished the arteriolar dilation observed in response to acetylcholine or bradykinin during venule to arteriole perfusion.

Conclusions: These results demonstrate that venular‐derived EDNO can relax arteriolar vascular smooth muscle.
Regulation of E‐Selectin, P‐Selectin, and Intercellular Adhesion Molecule 1 Expression in Mouse Cremaster Muscle Vasculature
Authors: Jung Unsu , Ley Klaus
Published: April 2008

Objective: To investigate the expression of P‐ and E‐selectin and intercellular adhesion molecule 1 (ICAM‐1) in the vasculature of mouse cremaster muscles both with and without tumor necrosis factor a (TNF‐α) treatment.

Methods: Mice received injections of monoclonal antibody to P‐selectin, E‐selectin, or ICAM‐1 before fixation to restrict detection to antigen expressed on the endothelial surface. Whole‐mount preparations of mouse cremaster muscles were fixed in acetone and stained using biotinylated secondary antibody and peroxidase‐conjugated streptavidin.

Results: P‐selectin is expressed on the endothelial surface of cremaster muscle venules within 10 minutes after exteriorization. Expression increases upon treatment with TNF‐α (2 hours), reflecting transcriptional regulation of P‐selectin expression in situ. The baseline E‐selectin expression is patchy and barely detectable but shows a significant upregulation after treatment with TNF‐α. ICAM‐1 is constitutively expressed in unstimulated mouse cremaster venules and slightly upregulated after 2 hours of TNF‐α treatment. Under baseline conditions, neither E‐selectin, P‐selectin, nor ICAM‐1 is detectable in arterioles or capillaries. After TNF‐α treatment, arterioles stain faintly for P‐selectin, but not E‐selectin or ICAM‐1.

Conclusion: The temporal and spatial pattern of expression of P‐ and E‐selectin and ICAM‐1 is consistent with the functional role of these molecules in mediating preferential leukocyte rolling and adhesion in mouse cremaster muscle venules.
Effects of Anastomoses on Solute Transcapillary Exchange in Countercurrent Systems
Authors: Wang W. , Michel C. C.
Published: April 2008

Objective: To investigate effects of anastomoses between the descending vasa recta (DVR) and the ascending vasa recta (AVR) on the distribution of small solutes in the interstitial fluid of the renal medulla.

Methods: Countercurrent capillary loops, surrounded by a secretory epithelium, were used to model microvessels in the renal medulla. Anastomoses between the DVR and AVR were modeled as a decrease in cross‐sectional area of the vessels and a decrease in flow velocity from the base to the tip of the capillary loop. When experimental data were used to evaluate parameters of the model, it was seen that diffusive transport of solute in the axial direction of the capillary was negligible, and the equations could be greatly simplified.

Results: General formulae of the solute concentration distribution were derived for different degrees of shunting between the two limbs of the capillary loop. Analytical solutions for the steady‐state solute distribution were obtained when the sizes of capillaries and flows in them were assumed to decrease linearly with the distance from the base to the tip of the capillary loop. When the effects of reduction in the size of the limbs were compared with the effects of reduction of flow velocities on solute distribution, it was found that, in the presence of anastomoses, change in flow velocity increases the axial gradient of the solute concentration more than change in the cross‐sectional area. The combined effects of a decrease in flow velocity and cross‐sectional area can easily double the axial gradient of the solute concentration for a modest degree of anastomotic shunting.

Conclusions: In this study, we separated effects of anastomotic flow between the DVR and AVR from other factors affecting the complicated countercurrent solute exchanges in the renal medulla. Results from the model show that anastomoses increase the solute concentration in the medullary interstitium and also the axial gradient of the solute concentration there.
Fractal Characteristics of Tumor Vascular Architecture During Tumor Growth and Regression
Authors: Gazit Yuval , Baish James W. , Safabakhsh Nina , Leunig Michael , Baxter Laurence T. , Jain Rakesh K.
Published: April 2008

Objective: Tumor vascular networks are different from normal vascular networks, but the mechanisms underlying these differences are not known. Understanding these mechanisms may be the key to improving the efficacy of treatment of solid tumors.

Methods: We studied the fractal characteristics of two‐dimensional normal and tumor vascular networks grown in a murine dorsal chamber preparation and imaged with an intravital microscopy station.

Results: During tumor growth and regression, the vasculature in the tumor has scaling characteristics that reflect the changing state of the tissue. Growing tumors show vascular networks that progressively deviate from their normal pattern, in which they seem to follow diffusion‐limited aggregation to a pathological condition in which they display scaling similar to percolation clusters near the percolation threshold. The percolation‐like scaling indicates that the key determinants of tumor vascular architecture are local substrate properties rather than gradients of a diffusing substance, such as an angiogenic growth factor. During tumor regression, the fractal characteristics of the vasculature return to an intermediate between those of growing tumors and those of healthy tissues. Previous studies have shown that percolation‐like scaling generally inhibits transport.

Conclusions: In the present context, the percolation‐like nature of tumor vasculature implies that tumor vascular networks possess inherent architectural obstacles to the delivery of diffusible substances such as oxygen and drugs.
Imaging of Oxygen Saturation and Distribution of Erythrocytes in Microvessels
Authors: Tateishi Norihiko , Suzuki Yoji , Tanaka Junya , Maeda Nobuji
Published: April 2008

Objective: To construct images of oxygen saturation and the distribution of erythrocytes in a network of microvessels.

Methods: The image of a small group of microvessels under an inverted microscope was incorporated into an image processor through a video camera and was digitized. Based on the information obtained through six visible interference filters of different wavelengths, oxygen saturation and the amount of erythrocytes in microvessels were calculated with a computer. The system was applied to a microvascular bed of isolated rabbit mesentery perfused with a suspension of human erythrocytes.

Results: In a steady flow, with lowering of tissue oxygen tension by superfusion with nitrogen‐bubbled isotonic saline containing 20 mmol/L sodium dithionite, the decrease of oxygen saturation of erythrocytes from arterioles to venules was imaged. Simultaneously, the distribution of erythrocytes in the microvessels was imaged and the marginal cell‐free layer was profiled under high magnification. No significant alteration of the erythrocyte distribution on the deoxygenation of erythrocytes was observed. The exposure of erythrocytes to acidic pH and the decrease of the flow velocity of erythrocytes increased the release of oxygen from the erythrocytes in microvessels.

Conclusions: The present method will be useful for the comprehensive analysis of oxygen transfer in the microvascular network, on the basis of both changes of the oxygen saturation and the flow behavior of erythrocytes.
Resistance to Blood Flow in Nonuniform Capillaries
Authors: Secomb T. W. , Hsu R.
Published: April 2008

Objective: Microvessels in living tissues are not uniform cylinders, and red blood cells (RBCs) are continually deformed when traversing them. This may contribute to higher resistance to blood flow observed in microvessels compared with that in corresponding uniform glass tubes. Here, a theoretical model was used to estimate flow resistance in nonuniform capillaries and its dependence on hematocrit, flow rate, and mechanical properties of RBCs.

Methods: Single‐file motion of RBCs through capillaries with sinusoidally varying cross‐sections was simulated, assuming axisymmetrical geometry. Effects of cell membrane shear viscosity and elasticity were included. Lubrication theory was used to describe the plasma flow.

Results: Predicted resistance to blood flow in capillaries with variable cross‐sections was substantially higher than in uniform vessels with the same mean diameters. Resistance depended on vessel geometry, flow rate, and hematocrit. At tube hematocrit 30%, the increase in resistance was 40%–58% when diameter varied between 4.5 and 6 μm with wavelength 20 μm and 58%–77% for variations between 4 and 5 μm with wavelength 10 μm. Larger relative increases in resistance were predicted for RBCs with increased membrane shear viscosity.

Conclusions: Effects of transient RBC deformations in irregular capillaries contribute significantly to blood flow resistance in capillaries. However, this effect is not sufficient to account for the flow resistance observed in living tissues.
Structural Changes in the Cardiac Microvasculature of the Rat in Response to Acute High Glucose Levels: A Comparison With Diabetes
Authors: Ward B. J. , Al‐haboubi H. A.
Published: April 2008

Objective: Isolated rat hearts were used to determine whether structural changes in the coronary microcirculation caused by diabetes mellitus occur soon after the onset of hyperglycemia and whether early changes might be reversed by return to normoglycemic conditions.

Methods: Three experimental groups of hearts were used. The perfusate was Krebs‐Henseleit medium with the addition of (a) 25 mmol/L glucose for 60 minutes, (b) as (a) followed by 5 mmol/L glucose for 30 minutes, and (c) hearts from diabetic rats perfused for 15 minutes. All the hearts were fixed and processed for electron microscopy. Measurements were made of various capillary dimensions and basal lamina thickness.

Results: The high glucose concentration caused an overall reduction in capillary dimensions which was partly reversed by reperfusion with 5 mmol/L glucose. Diabetic hearts showed enlarged whole capillary and luminal area and thinning of the endothelial cells without any change in cross‐sectional area. Endothelial gaps, consistent with increased permeability, were observed in the high glucose group but not in diabetic hearts. The basal lamina was thickened in all three experimental groups compared with controls.

Conclusions: The results show that morphological changes in the microcirculation occur much earlier than was previously thought and, with the possible exception of the basal lamina thickening, may be reversible.
The Resistance to Flow of Individual Human Neutrophils in Glass Capillary Tubes with Diameters between 4.65 and 7.75 μm
Authors: Shao Jin‐Yu , Hochmuth Robert M.
Published: April 2008

Objective: The resistance to flow of individual human neutrophils flowing through smooth‐walled glass capillary tubes at velocities ranging between 0 and 30 μm/s is measured for six different capillary tube diameters between 4.65 and 7.75 μm.

Methods: The experiments were performed with a micropipet manipulation system. The velocity of individual human neutrophils was measured under different constant pressures and compared to the velocity of the cell‐free fluid in the same tube. With the aid of a theory that describes the motion of a concentric, smooth‐walled, sausage‐shaped body in a tube, the experimental measurements are used to calculate an apparent gap width between the cell and the capillary wall.

Results: The maximum calculated gap width in the larger capillary tubes was on the order of 0.1 μm, whereas the minimum gap width in the smaller capillaries was about 0.015 μm. These small gap widths mean that even one neutrophil can cause a significant increase in the apparent viscosity when a cell flows through 100‐ to 200‐μm‐long capillary tubes. The neutrophils often exhibited a small static friction that tended to increase as the capillary diameter decreased. Maximum values for the adhesive force caused by the static friction were on the order of 80 pN.

Conclusions: Even a single white cell entirely within a capillary can cause a significant increase in the resistance of flow.
Can atmospheric input of nitrogen affect seed bank dynamics in habitats of conservation interest? The case of dune slacks
Authors: Plassmann Katharina , Brown Nigel , Jones M. Laurence M. , Edwards‐Jones Gareth
Published: April 2008

Questions: Does the increased atmospheric deposition of nitrogen, which can have major effects on the established vegetation of nutrient‐poor habitats, also impact germination from the soil seed bank?

Location: Coastal dune slacks at Newborough Warren, Wales, UK.

Methods: The effects of nitrogen addition (15 kg.ha‐1.a‐1) on seed germination from the soil seed bank were investigated using the seedling emergence method between September 2004 and February 2005.

Results: More seedlings emerged from fertilised samples than unfertilised controls. Most species showed enhanced germination after fertilisation with nitrogen, with seedling numbers statistically significantly greater in nitrogen addition samples in a quarter of species abundant enough for analysis. Species that responded positively to fertilisation were species with low Ellenberg indicator values indicative of infertile sites.

Conclusions: Most species showed increased germination after fertilisation with nitrogen, including early successional species normally growing in nutrient‐poor conditions. This suggests that the increased atmospheric deposition of nitrogen probably not only impacts on established vegetation, but also has the potential to alter seed bank dynamics.
Potenzielle Eichenwuchsgebiete und aktuelle Eichenmischwälder der Schweiz | Potential oak sites and actual mixed oak forests in Switzerland
Authors: Mühlethaler Urs , Reisner Yvonne , Rogiers Nele
Published: April 2008

On behalf of the Federal Office for the Environment (FOEN), the Swiss College for Agriculture established the basis to foster oak species in Switzerland. For this, the growth areas of three oak species, common oak (Quercus robur), sessile oak (Q. petraea) and pubescent oak (Q. pubescens) were assessed throughout the entire country. The assessment was based on their physiological potential, their natural growth area and on the appearance of the middle spotted woodpecker. In addition, the older mixed oak stands were surveyed. These fundamental data were collected with a geographical information system and analyzed for each canton. Altogether, approximately one-fourth of the Swiss forest area is suitable for oak. The natural oak growth area covers however 38 500 ha only. About 19 000 ha of forest are populated by the middle spotted woodpecker and extended older mixed oak forests are found on approximately 24 500 ha. According to the applied evaluation matrix, the greatest potential for fostering oak species lies in eight cantons: Aargau, Zürich, Solothurn, Thurgau, Vaud, BaselLandschaft, Ticino and Schaffhausen.
Para-[123I]iodo-L-phenylalanine in patients with pancreatic adenocarcinoma
Authors: Gouverneur E. , Schaefer A. , Raedle J. , Menges M. , Kirsch C.-M. , Samnick S. , Hellwig D.
Published: April 2008

Recently, p-[123I]iodo-L-phenylalanine (IPA) was clinically validated for brain tumour imaging. Preclinical studies demonstrated uptake of IPA into pancreatic adenocarcinoma suggesting its diagnostic application in patients with pancreatic tumours. The aim was to study the tumour uptake of IPA in patients with pancreatic adenocarcinoma and to analyse its biodistribution and dosimetry to assess the radiation dose resulting from its diagnostic use. Patients, methods: Seven patients with pancreatic adenocarcinoma underwent whole-body scintigraphies and SPECT up to 24 h after administration of 250 MBq of IPA. Tumour uptake of IPA was assessed visually. Time activity curves and the corresponding residence times were determined for whole-body, kidneys, liver, spleen, lung, heart content, brain, and testes. Mean absorbed doses for various organs and the effective dose were assessed based on the MIRD formalism using OLINDA/EXM. Results: IPA exhibited no accumulation in proven manifestations of pancreatic adenocarcinomas. IPA was exclusively eliminated by the urine and showed a delayed clearance from blood. Residence times were 0.26 ± 0.09 h for kidneys, 0.38 ± 0.19 h for liver, 0.15 ± 0.07 h for spleen, 0.51 ± 0.20 h for lungs, 0.22 ± 0.07 h for heart content, 0.11 ± 0.05 h for brain, 0.014 ± 0.005 h for testes and 6.4 ± 2.2 h for the remainder. The highest absorbed doses were determined in the urinary bladder wall and in the kidneys. According to the ICRP 60 the effective dose resulting from 250 MBq IPA was 3.6 ± 0.7 mSv. Conclusion: Para-[123I]iodo-L-phenylalanine can be used in diagnostic nuclear medicine with acceptable radiation doses. Besides its proven validity for brain tumour imaging, IPA does not appear to be suitable as tracer for pancreatic cancer.
Myocardial perfusion scintigraphy 2006 in Germany
Authors: Burchert W. , Bengel F. M. , Zimmermann R. , vom Dahl J. , Schäfer W. , Schober O. , Kluge R. , Schäfers M. , Lindner O.
Published: April 2008

Aim: This second survey was to deliver further information on myocardial perfusion scintigraphy (MPS) in Germany in 2006. Method: 351 questionnaires were evaluated: 207 private practices (PP), 117 hospitals (HO), 27 from university hospitals (UH). Results: MPS of 106 331 patients were reported, 85% were investigated with 99mTc-perfusion tracers. 74% [2005=72%] were performed in PP, 17% [2005=15%] in HO and 9% [2005=13%] in UH. PP, which participated in 2005 and 2006, demonstrated an increase by 3,9% (HO 0%, UH –13,0%). The type of stress was pharmacological in 27% [2005=22%]; 54% adenosine (of these 29% with exercise), 37% dipyridamole (of these 56% with exercise), and 9% dobutamine. Gated SPECT was performed in 42% [2005=36%] of all restand in 39% [2005=32%] of all stress MPS. An attenuation correction was used by 69 [2005=78] institutions. 40% of all MPS were performed in patients suspected to have CAD. 24% of all institutions reported changes in the use of MPS by competing methods. Conclusion: There is a small increase of MPS between 2005 and 2006 despite competing methods. Gated SPECT has experienced more acceptance. Suspicion of CAD is an important indication of MPS. In order to tap the full potential of MPS a gated SPECT should be performed routinely.