bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Mechanics of Vascular Cell Motility
Authors: SHUSTER C.B. , HERMAN I.M. 
Published: January 2010

ABSTRACTAlterations in vascular cell shape and motility occur during developmental processes and in response to injury. Similarly, during tumor vascularization and atherogenesis, endothelial and smooth muscle cells undergo motile and proliferative responses to extracellular cues. Recent inroads into our understanding of signal transduction have identified several candidate pathways by which the extracellular matrix‐ and growth factor‐mediated stimulation of vascular cell motility may be mediated. The multiple and divergent extracellular stimuli that stimulate vascular motile responses may converge on the cytoskeleton via a family of ras‐related GTPases. Biochemical analyses as well as examination of cytoskeletal dynamics in vivo indicate that actin polymerization at the forward aspects of spreading cytoplasm is capable of driving forward protrusion formation in the absence of a conventional actin motor. Actin polymerization at the plasma membrane of leading lamellae may be mediated both by de novo nucleation of actin filaments and the generation of free filament ends by uncapping the barbed ends of existing actin filaments. This review summarizes the most recent findings in extracellular‐cytoskeletal‐signal transduction, therein, providing a framework to explain the remarkable remodeling seen in the vasculature during developmental and disease‐related processes.
Effect of Flow on Hydraulic Conductivity and Reflection Coefficient of Rabbit Mesentery
Authors: PARAMESWARAN SANDHYA , BROWN LAURA V. , LAI‐FOOK STEPHEN J. 
Published: January 2010

ABSTRACTObjective: To measure the hydraulic conductivity and reflection coefficient for albumin, as defined by the Starling equation, in rabbit mesentery.Methods: A section of rabbit mesentery was fixed between two chambers filled with lactated Ringer solution. Flow (Q) of Ringer solution was measured across the mesentery at driving pressures (ΔP) between 1 and 6 cm H2O. Hydraulic conductivity was proportional to the slope of the Q‐ΔP curve. At constant ΔP (∼−2, −4, or −6 cm H2O), flow was measured at three different albumin concentration differences (0.5, 1, and 1.5/g/dl). Unstirred layer effects were minimized by magnetic stirrers. Reflection coefficient was the negative of the slope of the Q‐Δπ curve divided by the slope of the Q‐ΔP curve, where Δπ was the albumin osmotic pressure difference. Hydraulic conductivity was measured before and after testicular hyaluronidase was added to the Ringer solution.Results: There was no significant difference in conductivity per unit area (Lp) for the three different driving pressures. Hyaluronidase increased hydraulic conductivity significantly (p< 0.01) by 72 ± 56 %, indicating that hyaluronan and other glycosaminoglycans contributed to tissue fluid resistance. Reflection coefficient (σ) increased from 0.02 to 0.14 as flow increased eightfold.Conclusions: The results suggest that the mesentery tissue provides little restriction to the passage of albumin. The increase in conductivity in the presence of hyaluronidase indicates that tissue hyaluronan and other glycosaminoglycans provide fluid resistance to bulk flow.
Prediction of Permeability‐Surface Area Product Data by Continuous‐Distribution Pore Models
Authors: MCNAMEE JAMES E. , WOLF MATTHEW B. 
Published: January 2010

ABSTRACTObjective: To investigate the ability of continuous‐distribution pore models to accurately predict permeability‐surface area product (PS) experimental data in skeletal muscle.Methods: Models having a water‐only (WO) pathway and continuous distributions of microvascular transport‐pathway sizes were fit to solute reflection‐coefficient (σ) experimental data (∼0.5–16 nm Stokes radii) obtained from skeletal muscle to determine optimal parameter values. Without further modification, these models were used to predict experimental PS values obtained from the literature for small solutes ranging in size from NaCl to inulin and for three proteins, α‐lactalbumin, ovalbumin, and albumin (∼ 0.23–3.7 nm radii). The protein PSs were determined from fluorescent tracer‐diffusion curves and a nonlinear model of tracer diffusion in the cat hindlimb preparation. The model's PS predictions were compared to those of a discrete‐pore model previously developed and a fiber‐matrix (FM) model.Results: A log‐normal (LN) continuous pore‐size distribution plus WO‐pathway model (three free parameters) fit the σ data to within the 95% confidence intervals of each of eight solutes spanning a 32‐fold size range and was nearly as close to the data as was the two discrete‐pore plus WO‐pathway model (four free parameters). Both models closely described the PS data for nine solutes spanning a 14‐fold size range. The fit of a fiber‐matrix plus WO‐pathway model (three free parameters) to the σ data was much poorer than for the other models.Conclusions: The LN and two‐discrete‐pore models accurately describe σ and PS experimental data in cat and human skeletal muscle. Therefore, experimental data resulting from complex microvascular transport processes are well characterized by simple pore models.
Potentiation of Pulmonary Arteriolar Vasoconstriction to Endothelin‐1 by Inhibition of Nitric Oxide Synthesis in the Intact Lung
Authors: ROBERTS ANDREW M. , SLAAF DICK W. , JOSHUA IRVING G. 
Published: January 2010

ABSTRACTObjective: To observe pulmonary arteriolar effects of endothelin‐1 (ET‐1) in the intact lung and determine if constriction to ET‐1 is potentiated by inhibition of nitric oxide (NO) synthesis.Methods: In anesthetized male Sprague‐Dawley rats with open chest, the lungs were ventilated with air through the lower trachea andin vivoresponses of pulmonary arterioles were examined by video microscopy. Observations were made when the lungs were statically inflated with oxygen to a pressure of approximately 10 cm H2O for brief periods. A lens with a dipping cone was held at the pleural surface. ET‐1 (10−7–10−5 M; approximately 0.1 ml) was applied topically to the fluid layer under the dipping cone.Results: ET‐1 (10−6 M) constricted parent arterioles 60 ± 5 µm in diameter by 52 ± 12% (range: 20–100%) and branches 45 ± 3 µm in diameter by 36 ± 4% (19–48%). Constriction persisted and there was a dramatic long‐lasting decrease in flow. Alveolar walls quickly became pale, indicating reduced capillary perfusion. A lower concentration of ET‐1 (10−7 M) constricted (p< 0.05) parent arterioles 61 ± 4 µm in diameter by 7 ± 3% initially, and by 13 ± 8% after 14 ± 2 minutes, while smaller branches did not respond. In separate experiments, infusion of the NO synthase inhibitor L‐NAME (1 mg/kg per minute), modestly (10 ± 3%) decreased (p< 0.05) baseline parent arteriolar diameter from 72 ± 7 µm to 64 ± 5 µm. Branch diameter changed insignificantly from 42 ± 7 µm to 38 ± 7 µm. Afterl‐NAME, ET‐1 (10−7 M) constricted (p< 0.05) parent arterioles by 17 ± 4% initially and 40 ± 14% after 14 ± 2 minutes. Concurrently, branches constricted (p< 0.05) by 14 ± 4% and 26 ± 15%.Conclusions: Arterioles less than 80 µm in diameter were very responsive to ET‐1, which could be a factor in altering pulmonary microvascular resistance. Inhibition of NO synthesis appears to potentiate constriction to ET‐1.
Effect of Reactive Oxygen Metabolites on Endothelial Permeability: Role of Nitric Oxide and Iron
Authors: OKAYAMA NAOTSUKA , GRISHAM MATTHEW B. , KEVIL CHRISTOPHER G. , EPPIHIMER LOIS ANN , WINK DAVID A. , ALEXANDER J. STEVEN 
Published: January 2010

ABSTRACTObjective: We evaluated the effects of the xanthine oxidase (XO)‐derived reactive oxygen metabolites on the permeability of bovine pulmonary arteryendothelial monolayers and examined how iron and nitric oxide (NO) participate in these changes in permeability.Methods: Permeability was measured using a cell‐column chromatographic method in which monolayers were exposed to combinations of agents.Results: Exposure of monolayers to a superoxide/peroxide generator, xanthine (X, 0.1 mM)/XO (25 mU/mL), increased solute permeability after 10 minutes, but the same dose of either X or XO alone did not. Exposure of monolayers to peroxide (0.1 mM) also increased permeability, but only after 70 minutes. This X/XO permeability was attenuated by either catalase, superoxide dismutase, methionine (1 mM), an oxy‐radical scavenger, or desferrioxamine (0.1 mM), an iron chelator. Spermine NONOate (SNO), an NO donor, attenuated X/XO permeability at 0.1 mM, but this protection was not significant at 0.01 or 1 mM. Spermine NONOate (0.1 mM) did not alter the permeability produced by 0.1 mM peroxide. L‐N5‐(1‐iminoethyl)‐ornithine (10 µM), an NO synthase inhibitor, completely blocked peroxide‐, and partially attenuated X/XO‐mediated permeability. However, 3‐morphosynodiomine (SIN‐1, 1 mM) plus catalase (1,000 U/mL), a peroxynitrite generator, did not alter permeability.Conclusions: Xanthine/Xanthine Oxidase permeability involves peroxide, superoxide, oxy‐radicals, and iron. Endogenous NO may regulate peroxide‐, but not superoxide‐mediated permeability. The protective effects of exogenous NO on the X/XO permeability may represent interactions between superoxide, peroxide, and cell surface‐bound iron.
Ischemia‐Reperfusion: Mechanisms of Microvascular Dysfunction and the Influence of Risk Factors for Cardiovascular Disease
Authors: GRANGER D. NEIL 
Published: January 2010

ABSTRACTEndothelial cell function in all segments (arterioles, capillaries, and venules) of the microvasculature is compromised in tissues exposed to ischemia and reperfusion (I/R). This endothelial cell dysfunction is manifested as an impaired ability of arterioles to vasodilate, enhanced fluid filtration and leukocyte plugging in capillaries, and leukocyte‐endothelial cell adhesion and increased protein extravasation in venules. An imbalance in the production of reactive oxygen species and nitric oxide contributes to most of these responses. The risk factors for cardiovascular disease, hypercholesterolemia, diabetes, and hypertension all appear to exacerbate the microvascular responses to I/R. A common feature of the deleterious effects of these risk factors is the enhanced oxidant stress experienced by endothelial cells, which appears to promote leukocyte‐endothelial cell adhesion via transcription‐independent (early response) and dependent (late response) processes. The exaggerated endothelial barrier dysfunction elicited by I/R in hypercholesterolemic animals is linked to the enhanced leukocyte recruitment, while the enhanced protein extravasation in postischemic venules of diabetic animals occurs independently of leukocyte recruitment.
Mast Cell Degranulation and Parenchymal Cell Injury in the Rat Mesentery
Authors: COSTA JENNIFER J. , HARRIS ANTHONY G. , DELANO FRANK A. , ZWEIFACH BENJAMIN W. , SCHMID‐SCHÖNBEIN GEERT W. 
Published: January 2010

ABSTRACTObjective: The objective of this study was to explore the degree of parenchymal cell injury after mast cell degranulation by application of compound 48/80 (CMP 48/80) in the absence of adherent leukocytes in the rat mesentery.Methods: Rats were rendered leukopenic by injection of an antibody against leukocytes, and the mesentery was superfused with CMP 48/80 during intravital microscopy. The extent of cell injury was determined using a fluorescent cellviability indicator, propidium iodide (PI). In an additional group, mast cell degranulation with CMP 48/80 was prevented by using the mast cell stabilizer Ketotifen.Results: After a reduction in the number of circulating leukocytes, mast cell degranulation produced a mild increase in parenchymal cell injury. The injury levels significantly increased when individual regions of the mesentery were compared. Stabilization of the mast cells with Ketotifen reduced the injury to below baseline values.Conclusions: In the absence of leukocyte adhesion to the endothelium, mast cell degranulation contributes to parenchymal cell injury in the mesentery.
A Web‐Based Research Tool for Functional Genomics of the Microcirculation: The Leukocyte Adhesion Cascade
Authors: LEY KLAUS , BREWER KELLY , MOTON ALLEN 
Published: January 2010

ABSTRACTObjective: Currently, microvascular data are almost exclusively deposited in scholarly journals. With the increasing availability of molecular data and the construction of genomic databases, a need arises to organize physiological data in a more accessible format. The microcirculation is a functional system that spans all organ systems and shares certain characteristics of organization with metabolic pathways, which have successfully been organized around genomic information for several prokaryotes. Here, we present a web‐based research and teaching tool (http:hsc.Virginia.EDUmedicinebasic‐scibiomedley) that covers a small aspect of microcirculatory physiology, the leukocyte adhesion cascade.Methods: Currently, the site is organized in a flat‐text mode with hypertext links to GenBank, Medline, and online journals where available.Results: The web‐based research and education tool is useful for graduate student education, and as a research resource for genetic researchers interested in gene function and for physiologists and biomedical engineers interested in the molecular basis of the leukocyte adhesion cascade. Our effort is intended to be a beginning toward a distributed database for the microcirculation (microcirculation physiome, see http:www.bme.jhu.edunewsmicrophys).Conclusions: We invite all microvascular researchers to provide annotations and comments to make the research and teaching tool more useful to the scientific community.
Microvascular Perfusion and Transport in the Diabetic Heart
Authors: McDONAGH PAUL F. , HOKAMA JASON Y. 
Published: January 2010

ABSTRACTDiabetes is a chronic disease of metabolic dysfunction that is increasing worldwide. The hyperglycemia associated with diabetes causes significant protein alterations and an oxidative stress. In the heart, all cell types are affected by diabetes; the myocyte, the vasculature and the blood cells. Four out of five diabetics die from ischemic heart disease and stroke, suggesting that the diabetic is quite vulnerable to ischemic injury. It is important to understand the pathophysiologic changes that occur in the diabetic heart in order to develop thoughtful treatments to limit this serious complication. This review focuses on the anatomical and functional alterations that occur in the diabetic circulation of the heart, with emphasis on the coronary microcirculation. Coronary microvascular dysfunction combined with blood cellular alterations are presented to explain the amplified oxidative stress that occurs in the diabetic heart under ischemic conditions.
Propagation of Viral‐Size Particles in Lymph and Blood after Subcutaneous Inoculation
Authors: FOKIN ALEXANDER A. , ROBICSEK FRANCIS , MASTERS THOMAS N. , SCHMID‐SCHÖNBEIN GEERT W. , JENKINS SCERIA H. 
Published: January 2010

ABSTRACTObjective: We investigated the propagation of viral‐size particles by lymph and blood after subcutaneous injection.Methods: In the canine model, transport of [99mTc] sulfur colloid particles of different sizes was studied in different settings in venous blood and lymph for 45 minutes after inoculation.Results: The mean arrival time of particles in the blood was 2.10 ± 0.46 minutes and 8.87 ± 1.72 minutes in the lymph. Lymph flow in the canine leg was 28.79 ± 2.09 µl/min and was increased by leg massage. The particle concentration was 1000 times higher in the lymph fluid than in blood. Particle flux values were comparable in blood and lymph. The accumulation of particles in blood initially rose faster than in lymph. Accumulation in lymph rises slower but continues longer and reaches higher values. Ninety percent of the inoculum remains at the injection site for at least 45 minutes. Particle size matters more in blood distribution. Leg massage enhances particle transport by lymph.Conclusions: After subcutaneous injection, viral‐size particles initially arrive in the blood and later in the lymph. Accumulation in lymph and blood increases for a prolonged time after inoculation. Results suggest possibilities for limiting the spread of infectious matter by early local antiviral treatment.
Age‐Dependent Cerebral Hemodynamic Effects of Traumatic Brain Injury in Newborn and Juvenile Pigs
Authors: ARMSTEAD WILLIAM M. 
Published: January 2010

ABSTRACTTraumatic brain injury is one of the major causes of morbidity, mortality, and pediatric intensive care unit admissions of children. Although the effects of traumatic brain injury have been well described for adult animal models, few have investigated these effects in the newborn or have characterized such effects as a function of age using a single model of injury. Using a piglet model of brain injury, recent studies have shown that the cerebral hemodynamic effects and the corresponding mechanisms for such effects of injury vary as a function of age. This review discusses the types of traumatic brain injury, their models, and the role of species in such model choice. This review also describes the effects of brain injury on cerebral blood flow, metabolism, and cerebrovascular regulation as a function of age. Finally, this review presents evidence for potential mechanisms that may contribute to age‐dependent impaired cerebral hemodynamics following brain injury.
Theoretical Simulation of Oxygen Transport to Brain by Networks of Microvessels: Effects of Oxygen Supply and Demand on Tissue Hypoxia
Authors: SECOMB T.W. , HSU R. , BEAMER N.B. , COULL B.M. 
Published: January 2010

ABSTRACTObjective: Simulations of oxygen delivery by a three‐dimensional network of microvessels in rat cerebral cortex were used to examine how the distribution of partial pressure of oxygen (PO2) in tissue depends on blood flow and oxygen consumption rates.Methods: Network geometry was deduced from previously published scanning electron micrographs of corrosion casts. A nonlinear least‐squares method, using images obtained at three different angles, was used to estimate vessel locations. The network consisted of 50 segments in a region 140 µm × 150 µm × 160 µm. A Green's function method was used to predict the PO2 distribution. Effects of varying perfusion and consumption were examined, relative to a control state with consumption 10 cm3O2/100 g per min and perfusion 160 cm3/100 g per min.Results: In the control state, minimum tissue PO2 was 7 mm Hg. A Krogh‐type model with the same density of vessels, but with uniform spacing, predicted a minimum tissue PO2 of 23 mm Hg. For perfusion below 60% of control, tissue hypoxia (PO2 <1 mm Hg) was predicted. When perfusion was reduced by 75%, the resulting hypoxia could be eliminated by a 31% reduction in oxygen consumption rate.Conclusions: The simulations suggest that tissue hypoxia resulting from a severe decrease in brain perfusion, as can occur in stroke, may be avoided by a moderate decrease in oxygen consumption rate.
Role of Microcirculation in Transplantation
Authors: MENGER MICHAEL D. , VOLLMAR BRIGITTE 
Published: January 2010

ABSTRACTMicrocirculatory derangements in organ transplantation, characterized by capillary perfusion failure and inflammation‐associated leukocyte recruitment, are major determinants for the manifestation of graft dysfunction and destruction. Although preservation/cold storage, posttransplant reperfusion, and rejection have to be considered as individual factors that contribute to injury, recent studies have indicated that ischemia‐reperfusion‐associated events may trigger immune‐response‐mediated late rejection. There is major evidence that the microcirculatory derangements induced by cold preservation and reperfusion involve oxygen radicals, complement, phospholipase A2, leukotrienes, thromboxane, platelet‐activating factor, and endothelin‐1 as well as the activation and function of leukocytic and endothelial selectins, β2‐integrins, and ICAM‐1. This view is based on the fact that blockade or neutralization of these inflammatory mediators and adhesion molecules results in significant amelioration of microvascular graft dysfunction. In parallel, rejection‐mediated microcirculatory derangements may not only be ameliorated by immunosuppressive agents, such as cyclosporin, deoxyspergualin, or RS61443, but may, in addition, effectively be inhibited by counteracting oxygen radicals, complement, platelet‐activating factor, and adhesion molecules. The introduction of novel techniques for the study of the microcirculation in men, such as thermodiffusion and orthogonal polarization spectral imaging, may in the future assist in improving both early diagnosis of microcirculatory derangements and monitoring of appropriateness of therapy in clinical transplantation surgery.
Attenuation of Histamine‐Induced Endothelial Permeability Responses after Pacing‐Induced Heart Failure: Role for Endogenous Catecholamines
Authors: DYESS DONNA L. , HUNTER J. LESLIE , LAKEY JAMES R. , MOYER DARLENE , DOUGHERTY F. CARROLL , TOWNSLEY MARY I. 
Published: January 2010

ABSTRACTObjective: After congestive heart failure (CHF), lung endothelial permeability responses to a number of perturbations, including acute barotrauma, angiotensin II, and thapsigargin are blunted. Our hypothesis was that similar attenuation of permeability responses occurs in peripheral vascular beds after CHF. We compared peripheral microvascular permeability responses to the autacoid histamine in control dogs and in dogs paced to heart failure (245 bpm for ∼36 days). Since catecholamines attenuate autacoid‐induced increases in microvascular permeability in skin and muscle in normal animals, we also tested whether the known elevation in catecholamines in CHF was involved in any downregulation of permeability responses in this group.Methods: Control and paced dogs were anesthetized, intubated, and ventilated, and a hindpaw lymphatic cannulated. The reflection coefficient for total proteins (σ) was measured at baseline and during one‐hour, local intra‐arterial histamine infusion.Results: In controls, σ fell from 0.83 ± 0.02 to 0.73 ± 0.04 after histamine (p < 0.05), while in the paced group σ was no different from that at baseline (0.77 ± 0.02). To test whether this difference was due to endogenous catecholamines, dogs were pretreated with propranolol (controls only) or the specific β2‐antagonist ICI 118,551 prior to histamine infusion. After β‐blockade, histamine significantly reduced σ in both control (0.83 ± 0.01 to 0.55 ± 0.05) and paced (0.83 ± 0.01 to 0.57 ± 0.07) groups (p < 0.05).Conclusion: We conclude that endogenous catecholamines, acting via β2‐adrenergic receptors, attenuate the permeability response to histamine in pacing‐induced heart failure.
A Method for Detecting Chaos in Canine Myocardial Microcirculatory Red Cell Flux
Authors: BARCLAY KATHERINE D. , KLASSEN GERALD A. , YOUNG CHARLES 
Published: January 2010

ABSTRACTObjective: To determine whether red cell movement, as measured by laser Doppler velocimetry, in the capillary net of the beating heart is chaotic.Methods: Using two dog hearts, in situ red blood cell flux was measured at many sites. Simultaneously, epicardial arterial flow and left ventricular pressure were recorded via transit‐time flowmeter and catheter manometer, respectively. The presence or absence of chaos was tested by two methods: Lyapunov exponents and correlation dimension.Results: For capillary red cell flux, the Lyapunov was strongly positive at most sites. It was less so for coronary arterial flow and least for left ventricular pressure. Correlation dimension calculation was less able to distinguish the presence or absence of chaos in capillary red cell tissue flux, coronary arterial flow, and left ventricular pressure.Conclusions: Capillary red cell flux (movement of red cells in capillaries) is nonlinear, (i.e., chaotic). This complexity suggests that the primary control for oxygen delivery to cardiac myocytes by red blood cells resides in the microcirculation. Also, capillary red cell flux is bifractal, suggesting an ordering of control.