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Microvascular Permeability (microvascular + permeability)
Selected AbstractsSignal Transduction Pathways in Enhanced Microvascular PermeabilityMICROCIRCULATION, Issue 6 2000SARAH Y. YUAN ABSTRACT We have been investigating the molecular mechanisms underlying pathophysiological regulation of microvascular permeability on isolated venules and cultured venular endothelial monolayers. Physiological approaches have been employed in combination with molecular analyses to probe the signal transduction pathways leading to enhanced microvascular permeability. A newly developed technique of protein transfection into cells and intact microvessels enables the correlation of functional reactions and signaling events at the molecular level in a direct and specific fashion. The results indicate that inflammatory mediators increase microvascular permeability via intracellular signaling pathways involving the activation of phospholipase C, cytosolic calcium, protein kinase C, nitric oxide synthase, guanylate cyclase, and protein kinase G. In response to the signaling stimulation, complex biochemical and conformational reactions occur at the endothelial structural proteins. Specifically, myosin light-chain activation-mediated myosin light-chain phosphorylation can result in cell contraction. VE-cadherin and ,-catenin phosphorylation may induce dissociation of the junctional proteins and their connection to the cytoskeleton, leading to a loose or opened intercellular junction. Focal adhesion phosphorylation and redistribution further provide an anchorage support for the conformational changes in the cells and at the cell junction. The three processes may act in concert to facilitate the flux of fluid and macromolecules across the microvascular endothelium. [source] Femur window,a new approach to microcirculation of living bone in situJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 5 2005N. Hansen-Algenstaedt Abstract Background: The processes of osteogenesis, bone remodelling, fracture repair and metastasis to bone are determined by complex sequential interactions involving cellular and microcirculatory parameters. Consequently studies targeting the analysis of microcirculatory parameters on such processes should mostly respect these complex conditions. However these conditions could not yet be achieved in vitro and therefore techniques that allow a long-term observation of functional and structural parameters of microcirculation in bone in vivo at a high spatial resolution are needed to monitor dynamic events, such as fracture healing, bone remodelling and tumor metastasis. Methods: We developed a bone chamber implant (femur window) for long-term intravital microscopy of pre-existing bone and its microcirculation at an orthotopic site in mice preserving the mechanical properties of bone. After bone chamber implantation vascular density, vessel diameter, vessel perfusion, vascular permeability and leukocyte-endothelial interactions (LEIs) in femoral bone tissue of c57-black mice (n = 11) were measured quantitatively over 12 days using intravital fluorescence microscopy. Furthermore a model for bone defect healing and bone metastasis in the femur window was tested. Results: Microvascular permeability and LEIs showed initially high values after chamber implantation followed by a significant decrease to a steady state at day 6 and 12, whereas structural parameters remained unaltered. Bone defect healing and tumor growth was observed over 12 and 90 days respectively. Conclusion: The new femur window design allows a long-term analysis of structural and functional properties of bone and its microcirculation quantitatively at a high spatial resolution. Altered functional parameters of microcirculation after surgical procedures and their time dependent return to a steady state underline the necessity of long-term observations to achieve unaltered microcirculatory parameters. Dissection of the complex interactions between bone and microcirculation enables us to evaluate physiological and pathological processes of bone and may give new insights especially in dynamic events e.g. fracture healing, bone remodeling and tumor metastasis. © 2005 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved. [source] Norepinephrine causes a pressure-dependent plasma volume decrease in clinical vasodilatory shockACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 7 2010A. NYGREN Background: Recent experimental studies have shown that a norepinephrine-induced increase in blood pressure induces a loss of plasma volume, particularly under increased microvascular permeability. We studied the effects of norepinephrine-induced variations in the mean arterial pressure (MAP) on plasma volume changes and systemic haemodynamics in patients with vasodilatory shock. Methods: Twenty-one mechanically ventilated patients who required norepinephrine to maintain MAP ,70 mmHg because of septic/postcardiotomy vasodilatory shock were included. The norepinephrine dose was randomly titrated to target MAPs of 60, 75 and 90 mmHg. At each target MAP, data on systemic haemodynamics, haematocrit, arterial and mixed venous oxygen content and urine flow urine were measured. Changes in the plasma volume were calculated as 100 × (Hctpre/Hctpost,1)/ (1,Hctpre), where Hctpre and Hctpost are haematocrits before and after intervention. Results: Norepinephrine doses to obtain target MAPs of 60, 75 and 90 mmHg were 0.20±0.18, 0.29±0.18 and 0.42±0.31 ,g/kg/min, respectively. From 60 to 90 mmHg, increases in the cardiac index (15%), systemic oxygen delivery index (25%), central venous pressure (CVP) (20%) and pulmonary artery occlusion pressure (33%) were seen, while the intrapulmonary shunt fraction was unaffected by norepinehrine. Plasma volume decreased by 6.5% and 9.4% (P<0.0001) when blood pressure was increased from 60 to 75 and 90 mmHg, respectively. MAP (P<0.02) independently predicted the decrease in plasma volume with norepinephrine but not CVP (P=0.19), cardiac index (P=0.73), norepinephrine dose (P=0.58) or urine flow (P=0.64). Conclusions: Norepinephrine causes a pressure-dependent decrease in the plasma volume in patients with vasodilatory shock most likely caused by transcapillary fluid extravasation. [source] Dynamic contrast-enhanced magnetic resonance imaging as a surrogate marker of tumor response to anti-angiogenic therapy in a xenograft model of glioblastoma multiformeJOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 3 2002Axel Gossmann MD Abstract Purpose To evaluate the effects of a neutralizing anti-vascular endothelial growth factor (anti-VEGF) antibody on tumor microvascular permeability, a proposed indicator of angiogenesis, and tumor growth in a rodent malignant glioma model. Materials and Methods A dynamic contrast-enhanced magnetic resonance imaging (MRI) technique, permitting noninvasive in vivo and in situ assessment of potential therapeutic effects, was used to measure tumor microvascular characteristics and volumes. U-87, a cell line derived from a human glioblastoma multiforme, was implanted orthotopically into brains of athymic homozygous nude rats. Results Treatment with the monoclonal antibody A4.6.1, specific for VEGF, significantly inhibited tumor microvascular permeability (6.1 ± 3.6 mL min,1100 cc,1), compared to the control, saline-treated tumors (28.6 ± 8.6 mL min,1100 cc,1), and significantly suppressed tumor growth (P < .05). Conclusion Findings demonstrate that tumor vascular permeability and tumor growth can be inhibited by neutralization of endogenous VEGF and suggest that angiogenesis with the maintenance of endothelial hyperpermeability requires the presence of VEGF within the tissue microenvironment. Changes in tumor vessel permeability and tumor volumes as measured by contrast-enhanced MRI provide an assay that could prove useful for clinical monitoring of anti-angiogenic therapies in brain tumors. J. Magn. Reson. Imaging 2002;15:233,240. © 2002 Wiley-Liss, Inc. [source] Pathology of lumbar nerve root compression Part 1: Intraradicular inflammatory changes induced by mechanical compressionJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 1 2004Shigeru Kobayashi Study design: This study is to investigate the intraradicular inflammation induced by mechanical compression using in vivo model. Objectives: The relationship between the intraradicular edema and nerve fiber degeneration induced by mechanical compression was determined in the nerve root. Summary of background data: Recently some studies reported that mechanical compression increased microvascular permeability of the endoneurial capillaries and resulted in an intraradicular inflammation. These changes may be an important factor of the pathogenesis of radiculopathy. However, the natural courses of the intraradicular inflammation after mechanical compression are still poorly understood. Methods: In dogs, laminectomy was performed at L7 and the seventh nerve root was exposed to compression at 7.5 gram force (gf) clipping power. The animals were evaluated at 1 and 3 weeks after clipping. After the appropriate period of nerve root compression, Evans blue albumin (EBA) was injected intravenously. The nerve root sections were divided into two groups. The sections were used to investigate the status of the blood,nerve barrier function under the fluorescence microscope. The other sections were used for light and transmission electron microscopic study. Results: After 1 and 3 weeks, intraradicular edema was observed not only at the site of compression but also in the peripheral zone of a compressed anterior root and in the central zone of a compressed posterior root. The evidence of active Wallerian degeneration was also seen in the area of intraradicular edema. In addition, the nerve roots showing Wallerian degeneration were infiltrated by inflammatory cells, such as macrophages and mast cells. Conclusions: Inflammatory reaction, such as Wallerian degeneration, breakdown of blood,nerve barrier and appearance of macrophage, may be deeply involved in radiculitis arising from mechanical compression, and these factors seem to be important in the manifestation of radiculopathy. © 2003 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved. [source] Hyperglycemia Stimulates a Sustained Increase in Hydraulic Conductivity In Vivo without Any Change in Reflection CoefficientMICROCIRCULATION, Issue 7 2007RACHEL M. PERRIN ABSTRACT Objective: Increased microvascular permeability contributes to the development of diabetic microvascular complications and diabetic vasculopathy is correlated with blood glucose levels. The mechanisms underlying increased permeability, however, are poorly understood. Methods: The Landis-Michel technique was used to measure water permeability (hydraulic conductivity, Lp) and macromolecular permeability (reflection coefficient, ,) of exchange capillaries in frogs and rats. Results: Dialysed normoglycemic plasma from diabetic patients had no effect on Lp. The same plasma with 20 mM glucose increased hydraulic conductivity from (mean ± SEM × 10,7 cm · s,1· cm H2O,1) 5.73 ± 2.01 to 13.09 ± 2.67 (P < .01). Nondiabetic control plasma did not affect Lp, but addition of 20 mM glucose increased Lp to a similar degree. The effect of glucose alone was examined. Glucose at 20 mM increased Lp, from 2.82 ± 0.61 to 4.71 ± 1.35 × 10, 7 cm · s, 1· cm H2O,1 (P = .002, n = 13). A similar increase was seen in rat mesenteric microvessels, from 1.04 ± 0.40 in control perfusions to 2.18 ± 0.56, P < .05. The microvascular macromolecular reflection coefficient in all the above experiments was unaltered. The use of specific inhibitors indicated that the glucose-induced increased Lp did not appear to be mediated through protein kinase C (PKC), free radical generation, glucose metabolism, or albumin glycation. Conclusions: These data suggest that hyperglycemia induced increased apparent protein permeability may be secondary to a glucose-mediated change in macromolecular convective flux rather than any change in protein permeability per se. The authors speculate that the increased microvascular permeability to water in vivo is mediated by direct interaction of glucose with the endothelial cells (perhaps with the glycocalyx). [source] Extravascular Transport of Fluorescently Labeled Albumins in the Rat MesenteryMICROCIRCULATION, Issue 3 2002NORMAN R. HARRIS ABSTRACT Objective: Fluorescently labeled albumin is used frequently as a tracer when monitoring microvascular permeability. Several fluorescent dyes are available for labeling protein, including fluorescein isothiocyanate (FITC) and Texas Red (TR). Because differences in leakage of dye-labeled proteins have been reported, the objective of the present study was to compare the accumulation of these two tracers in interstitium and lymph after the inflammatory event of ischemiareperfusion. Methods: Anesthetized rats were injected intravenously with FITC-labeled albumin (FITC-alb) and TR-labeled albumin (TR-alb) before 30 minutes of mesenteric ischemia. Because the tracers leaked out of the microcirculation after reperfusion, accumulation in the surrounding buffer-superfused tissue, and in separate experiments, accumulation in lymph vessels, was defined as the ratio of tissue-to-plasma and lymph-to-plasma fluorescence. Results: Reperfusion induced a significant increase in tissue-to-plasma fluorescence of FITC-alb; however, no increase was observed for TR-alb. In contrast, lymph-to-plasma fluorescence of TR-alb tended to be greater than FITC-alb. Reperfusion-induced increases in tissue-to-plasma fluorescence of TR-alb occurred only when the superfusate was replaced with mineral oil, in which case tissue-to-plasma TR-alb fluorescence tended to be greater than FITC-alb. Conclusions: Measurement of fluorescently labeled albumin leakage from mesenteric venules depends on the dye used to label the albumin and requires an assessment of losses from the extravascular measuring region. [source] Signal Transduction Pathways in Enhanced Microvascular PermeabilityMICROCIRCULATION, Issue 6 2000SARAH Y. YUAN ABSTRACT We have been investigating the molecular mechanisms underlying pathophysiological regulation of microvascular permeability on isolated venules and cultured venular endothelial monolayers. Physiological approaches have been employed in combination with molecular analyses to probe the signal transduction pathways leading to enhanced microvascular permeability. A newly developed technique of protein transfection into cells and intact microvessels enables the correlation of functional reactions and signaling events at the molecular level in a direct and specific fashion. The results indicate that inflammatory mediators increase microvascular permeability via intracellular signaling pathways involving the activation of phospholipase C, cytosolic calcium, protein kinase C, nitric oxide synthase, guanylate cyclase, and protein kinase G. In response to the signaling stimulation, complex biochemical and conformational reactions occur at the endothelial structural proteins. Specifically, myosin light-chain activation-mediated myosin light-chain phosphorylation can result in cell contraction. VE-cadherin and ,-catenin phosphorylation may induce dissociation of the junctional proteins and their connection to the cytoskeleton, leading to a loose or opened intercellular junction. Focal adhesion phosphorylation and redistribution further provide an anchorage support for the conformational changes in the cells and at the cell junction. The three processes may act in concert to facilitate the flux of fluid and macromolecules across the microvascular endothelium. [source] Attenuation of Histamine-Induced Endothelial Permeability Responses after Pacing-Induced Heart Failure: Role for Endogenous CatecholaminesMICROCIRCULATION, Issue 5 2000DONNA L. DYESS ABSTRACT Objective: 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 (,) was measured at baseline and during one-hour, local intra-arterial histamine infusion. Results: In controls, , fell from 0.83 ± 0.02 to 0.73 ± 0.04 after histamine (p < 0.05), while in the paced group , 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 ,2 -antagonist ICI 118,551 prior to histamine infusion. After ,-blockade, histamine significantly reduced , 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 ,2 -adrenergic receptors, attenuate the permeability response to histamine in pacing-induced heart failure. [source] Baicalin attenuates air embolism-induced acute lung injury in rat isolated lungsBRITISH JOURNAL OF PHARMACOLOGY, Issue 2 2009Min-Hui Li Background and purpose:, Baicalin has been reported to have anti-inflammatory effects and protect against various tissue injuries. However, the effect of baicalin on air embolism-induced acute lung injury has not been tested yet. Experimental approach:, Acute lung injury was induced by infusion of air at a rate of 0.25 mL·min,1 for 1 min into the pulmonary artery of rat isolated lungs. At the end of the experiment, samples were collected for assessment of lung injury, biochemical analysis and histology. Different doses of baicalin (1, 2 and 4 mg·kg,1) were given into the perfusate before air infusion. Key results:, Air embolism elicited a significant increase in microvascular permeability (Kf), lung weight gain, wet/dry weight ratio, pulmonary artery pressure and protein concentration in the bronchoalveolar lavage fluid. Levels of the cytokines, tumour necrosis factor , and cytokine-induced neutrophil chemoattractant-1 in perfusate, and malondialdehyde levels and myeloperoxidase activities in lung tissue were also significantly increased. In addition, histological examination showed increased neutrophil infiltration in lung tissues. Furthermore, nuclear factor-,B activity and degradation of I,B-, were significantly increased in lungs. Pretreatment of the lungs with baicalin (4 mg·kg,1) showed a statistically significant difference in all of the assessed parameters, except for alteration in the pulmonary artery pressure. Conclusions and implications:, Our study suggests that baicalin attenuated air embolism-induced acute lung injury and may be considered a useful adjunct drug therapy in this clinical condition. [source] | ||||||||||