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Microcirculation
Kinds of Microcirculation Selected AbstractsINVESTIGATION OF THE MICROCIRCULATION AND THE STATE OF OXIDATIVE STRESS IN THE RAT AFTER SCORPION ENVENOMATIONCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 4 2007Z Sahnoun SUMMARY 1Severe cases of scorpion envenomation (SE) generally show both respiratory and cardiocirculatory dysfunction. However, the pathophysiology of SE remains controversial. In the present study, we tried to explain the pathophysiology of the haemodynamic perturbations and cardiac failure in rats poisoned by the venom of Buthus occitanus tunetanus through a histomorphometric study of myocardial and muscular skeletal microcirculation and analysis of the oxidative stress state in order to evaluate the implication of the inflammatory process in the pathogenesis of SE. 2Experiments were performed on 96 rats divided into 16 groups (n = 6 in each group). Two groups were used to determine the optimum conditions of venom administration and times when to measure haemodynamic parameters. The B. occitanus tunetanus venom was administered at a dose of 800 µg/kg and tissues were removed 5 and 20 min after envenomation. Six groups were used for histomorphometric study: two control groups, two poisoned groups an two melatonin-pretreated and poisoned groups. The histomorphometric study was performed on isolated hearts and skeletal muscles. The final eight groups of rats (two control groups, two envenomated groups, two control groups pretreated with melatonin and two groups pretreated and envenomated) were used to investigate the state of tissue oxidative stress during SE and to evaluate the anti-oxidant effect of melatonin on rats poisoned with B. occitanus tunetanus venom. This study was based on the determination of tissue malondialdehyde in isolated organs as an indicator of thiobarbituric acid-reactive substances (TBARS). Melatonin was injected at a dose of 5 mg/kg, i.v., 15 min before the administration of serum or venom. Data were compared using analysis of variance and Tukey's test for multiple pair-wise comparisons. 3Five minutes after venom injection, a significant reduction in the mean relative volume of venules and arterioles in the heart and skeletal muscles of poisoned rats was noted. Twenty minutes after venom injection, these volumes were significantly increased in the heart and skeletal muscles of poisoned rats. Pretreatment of envenomated rats with melatonin resulted in a significant decrease in the mean relative volume of the venules and arterioles in the heart and skeletal muscles 5 and 20 min after venom injection compared with untreated envenomated rats. Investigation of the oxidative stress state showed a highly significant increase in TBARS in poisoned rats compared with control groups 5 and 20 min after venom injection. Melatonin pretreatment of rats poisoned with B. occitanus tunetanus venom resulted in an important and highly significant reduction of TBARS compared with untreated envenomated rats. 4It appears from the results of the present study that administration of B. occitanus tunetanus venom engendered an excessive myocardial and skeletal muscular vasoconstriction attributed to massive catecholamine release followed by arteriolar and venular vasodilatation. This venous stasis at the muscular microcirculation could be due to myocardiac failure. However, the concomitant presence of arteriolar vasodilatation suggests an inflammatory process in the pathophysiology of SE. This process was suggested by the genesis of a state of oxidative stress in relation to the important lipoperoxidation, which was inhibited by administration of the anti-oxidant melatonin. Thus, melatonin pretreatment seemed to accentuate the first phase of vascular reactivity in envenomed rats and inhibit the second vasodilator phase observed 20 min after administration of the venom. [source] Regression of Alterations in Retinal Microcirculation Following Treatment for Arterial HypertensionJOURNAL OF CLINICAL HYPERTENSION, Issue 8 2006Antonio Pose-Reino MD Evaluation of early hypertension-related alterations in retinal microcirculation has been subjective and poorly reproducible. The authors recently described a semiautomatic computerized system for evaluation of the calibre of retinal blood vessels that has shown very good reproducibility. In the study, this system was used to measure the calibres of retinal arterioles and veins, and their ratio, in a group of 51 hypertensive outpatients before and after 6 months of treatment with losartan or, if required for satisfactory blood pressure control, losartan plus hydrochlorothiazide. Mean retinal arteriole diameter increased from 0.0842±0.003 mm to 0.0847±0.003 mm (p=0.001). Arteriovenous ratio increased from 0.753±0.03 to 0.756±0.03 (p=0.005). This observation suggests regression of early hypertension-related alterations in retinal microcirculation after 6 months of antihypertensive treatment. [source] Expression Of O-Acetyl Sialic Acid On Cerebral Microcirculation In A Glycine Or Taurine Treated Diabetic Rat ModelJOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 3 2000A Noe Expression of sialic acid is altered in Diabetes mellitus. This modification has also been involved with both vascular and neurologic diseases, and with the increase of no enzymatic glycosylation of proteins. In our opinion, the lectins were very useful with specificity for sialic acids in order to determine the level of sialic acid expression on cerebral microcirculation in a diabetic Wistar rat model with streptozotocin. In this model, the glycine (1%) and taurine (0.5%) aminoacids were placed in drinking-water by six months. At the end of this time, the animals were sacrificed, their brains surgically removed and frozen in liquid nitrogen, and the specimens cut in serial sections. Immediately, the sections were incubated with different biotin-labelled lectins specific to sialic acid using peroxidase-labelled avidin as second ligand and H2O2 chromogen. The results showed greater O-acetyl sialic acid expression in cerebral capillaries of untreated diabetic rats than in glycine-, taurine-treated diabetic rats or than in control animals. The minor sialic acid expression may be an indicator of degenerative diseases such as Alzheimer's or the vascular disease of diabetic patients and probably is related to cellular protective properties of the glycine and taurine aminoacids. These first protective characteristics that have been observed in both ischemia with cellular ATP depletion models, suggest the utilization of aminoacids glycine or taurine in diabetic patient in order to avoid the development of microinfarcts. [source] Collateral Capillary Arterialization following Arteriolar Ligation in Murine Skeletal MuscleMICROCIRCULATION, Issue 5 2010FEILIM MAC GABHANN Microcirculation (2010) 17, 333,347. doi: 10.1111/j.1549-8719.2010.00034.x Abstract Objective:, Chronic and acute ischemic diseases,peripheral artery disease, coronary artery disease, stroke,result in tissue damage unless blood flow is maintained or restored in a timely manner. Mice of different strains recover from arteriolar ligation (by increasing collateral blood flow) at different speeds. We quantify the spatio-temporal patterns of microvascular network remodeling following arteriolar ligation in different mouse strains to better understand inter-individual variability. Methods:, Whole-muscle spinotrapezius microvascular networks of mouse strains C57Bl/6, Balb/c and CD1 were imaged using confocal microscopy following ligation of feeding arterioles. Results:, Baseline arteriolar structures of C57Bl/6 and Balb/c mice feature heavily ramified arcades and unconnected dendritic trees, respectively. This network angioarchitecture identifies ischemia-protected and ischemia-vulnerable tissues; unlike C57Bl/6, downstream capillary perfusion in Balb/c spinotrapezius is lost following ligation. Perfusion recovery requires arterialization (expansion and investment of mural cells) of a subset of capillaries forming a new low-resistance collateral pathway between arteriolar trees. Outbred CD1 exhibit either Balb/c-like or C57Bl/6-like spinotrapezius angioarchitecture, predictive of response to arteriolar ligation. Conclusions:, This collateral capillary arterialization process may explain the reported longer time required for blood flow recovery in Balb/c hindlimb ischemia, as low-resistance blood flow pathways along capillary conduits must be formed ("arterialization") before reperfusion. [source] Inhibition of Canonical Wnt Signaling Increases Microvascular Hemorrhaging and Venular Remodeling in Adult RatsMICROCIRCULATION, Issue 5 2010JASON T. GLAW Microcirculation (2010) 17, 348,357. doi: 10.1111/j.1549-8719.2010.00036.x Abstract Objective:, The canonical Wnt signaling pathway, heavily studied in development and cancer, has recently been implicated in microvascular growth with the use of developmental and in vitro models. To date, however, no study exists showing the effects of perturbing the canonical Wnt pathway in a complete microvascular network undergoing physiological remodeling in vivo. Our objective was to investigate the effects of canonical Wnt inhibition on the microvascular remodeling of adult rats. Methods:, Canonical Wnt inhibitor DKK-1, Wnt inhibitor sFRP-1, BSA or saline was superfused onto the exteriorized mesenteric windows of 300 g adult female Sprague-Dawley rats for 20 minutes. Three days following surgery, mesenteric windows were imaged intravitally and harvested for immunofluorescence staining with smooth muscle alpha-actin and BRDU. Results:, We observed prominent differences in the response of the mesenteric microvasculature amongst the various treatment groups. Significant increases in hemorrhage area, vascular density, and draining vessel diameter were observed in windows treated with Wnt inhibitors as compared to control-treated windows. Additionally, confocal imaging analysis showed significant increases in proliferating cells as well as evidence of proliferating smooth muscle cells along venules. Conclusions:, Together, our results suggest that canonical Wnt inhibition plays an important role in microvascular remodeling, specifically venular remodeling. [source] Progressive Renal Vascular Proliferation and Injury in Obese Zucker RatsMICROCIRCULATION, Issue 4 2010RADU ILIESCU Microcirculation (2010) 17, 250,258. doi: 10.1111/j.1549-8719.2010.00020.x Abstract Objective:, Obesity, an independent risk factor for chronic kidney disease, may induce renal injury by promoting inflammation. Inflammatory cytokines can induce neovascularization in different organs, including the kidneys. However, whether obesity triggers renal neovascularization and, if so, its effect on renal function has never been investigated. Methods:, Blood pressure, proteinuria, and glomerular filtration rate (GFR) were measured in vivo. Renal microvascular (MV) architecture was studied by 3D micro-CT in lean and obese Zucker rats (LZR and OZR, n = 7/group) at 12, 22, and 32 weeks of age. Renal inflammation was assessed by quantifying interleukin (IL)-6, tumor necrosis factor (TNF)-alpha, and ED-1 expression, as renal fibrosis in trichrome-stained cross-sections. Results:, Mild inflammation and lower GFR was only observed in younger OZR, without renal fibrosis or changes in MV density. Interestingly, renal MV density increased in OZR at 32 weeks of age, accompanied by pronounced increase in renal IL-6 and TNF-alpha, ED-1+ cells, proteinuria, decreased GFR, and fibrosis. Conclusions:, This study shows increased renal cortical vascularization in experimental obesity, suggesting neovascularization as an evolving process as obesity progresses. Increased renal vascularization, possibly triggered by inflammation, may reflect an initially compensatory mechanism in obesity. However, increased inflammation and inflammatory-induced neovascularization may further promote renal injury as obesity advances. [source] Proteomic Analysis of Shear Stress-Mediated Protection from TNF-, in Endothelial CellsMICROCIRCULATION, Issue 4 2010Julie K. Freed Microcirculation (2010) 17, 259,270. doi: 10.1111/j.1549-8719.2010.00031.x Abstract Previous studies have shown that physiological levels of shear stress can protect endothelial cells (ECs) from apoptotic stimuli. Here, we differentiate between acute and chronic protection and demonstrate the use of proteomic technologies to uncover mechanisms associated with chronic protection of ECs. We hypothesized that changes in abundance of proteins associated with the TNF-, signaling cascade orchestrate shear stress-mediated protection from TNF-, when cells are preconditioned with shear prior to the exposure of apoptotic stimuli. Detection of cleaved caspase 3 through Western blot analysis confirmed chronic shear stress-mediated protection from TNF-,. In the presence of the nitric oxide synthase inhibitor, LNMA (N, -monomethyl- l -arginine), chronic protection remained. Treatment with a de novo protein synthesis inhibitor, cycloheximide, eliminated this protective effect. Isotopic-labeling experiments, coupled with LC,MS/MS (liquid chromatography,tandem mass spectrometry) of isolated components of the TNF-, pathway revealed that CARD9, a known activator of the NF-,B pathway, was increased (60%) in sheared cells versus nonsheared cells. This result was confirmed through Western blot analysis. Our data suggest that de novo formation of proteins is required for protection from TNF-, in ECs chronically exposed to shear stress, and that CARD9 is a candidate protein in this response. [source] The Effects of Hemodynamic Force on Embryonic DevelopmentMICROCIRCULATION, Issue 3 2010JAMES C. CULVER Microcirculation (2010) 17, 164,178. doi: 10.1111/j.1549-8719.2010.00025.x Abstract Blood vessels have long been known to respond to hemodynamic force, and several mechanotransduction pathways have been identified. However, only recently have we begun to understand the effects of hemodynamic force on embryonic development. In this review, we will discuss specific examples illustrating the role of hemodynamic force during the development of the embryo, with particular focus on the development of the vascular system and the morphogenesis of the heart. We will also discuss the important functions served by mechanotransduction and hemodynamic force during placentation, as well as in regulating the maintenance and division of embryonic, hematopoietic, neural, and mesenchymal stem cells. Pathological misregulation of mechanosensitive pathways during pregnancy and embryonic development may contribute to the occurrence of cardiovascular birth defects, as well as to a variety of other diseases, including preeclampsia. Thus, there is a need for future studies focusing on better understanding the physiological effects of hemodynamic force during embryonic development and their role in the pathogenesis of disease. [source] Mechanobiology and the Microcirculation: Cellular, Nuclear and Fluid MechanicsMICROCIRCULATION, Issue 3 2010KRIS NOEL DAHL Microcirculation (2010) 17, 179,191. doi: 10.1111/j.1549-8719.2009.00016.x Abstract Endothelial cells are stimulated by shear stress throughout the vasculature and respond with changes in gene expression and by morphological reorganization. Mechanical sensors of the cell are varied and include cell surface sensors that activate intracellular chemical signaling pathways. Here, possible mechanical sensors of the cell including reorganization of the cytoskeleton and the nucleus are discussed in relation to shear flow. A mutation in the nuclear structural protein lamin A, related to Hutchinson-Gilford progeria syndrome, is reviewed specifically as the mutation results in altered nuclear structure and stiffer nuclei; animal models also suggest significantly altered vascular structure. Nuclear and cellular deformation of endothelial cells in response to shear stress provides partial understanding of possible mechanical regulation in the microcirculation. Increasing sophistication of fluid flow simulations inside the vessel is also an emerging area relevant to the microcirculation as visualization in situ is difficult. This integrated approach to study,including medicine, molecular and cell biology, biophysics and engineering,provides a unique understanding of multi-scale interactions in the microcirculation. [source] Rapid Vasodilation in Isolated Skeletal Muscle Arterioles: Impact of Branch OrderMICROCIRCULATION, Issue 2 2010BRUNO T. ROSEGUINI Microcirculation (2010) 17, 1,11. doi: 10.1111/j.1549-8719.2009.00005.x Abstract We tested the hypothesis that segmental differences in the responsiveness and time course of vasodilation to metabolic signals putatively involved in rapid onset vasodilation (ROV) at the start of exercise exist within the skeletal muscle vasculature. Cannulated first-order (1As) and third-order arterioles (3As) of the rat gastrocnemius (G) muscle were exposed to cumulative doses of KCl, acetylcholine (Ach), or adenosine (Ado). In addition, time course and magnitude of vasodilation to localized application of these agonists were determined. 1As and 3As dilated similarly to incremental doses of the agonists. Continuous monitoring of internal diameter revealed a fast and transient dilatory response to microinjections of the agonists, with an average time delay (TD) before the onset of vasodilation of 2.8 ± 0.2 seconds (1As: 3.0 ± 0.3 seconds and 3As: 2.6 ± 0.3 seconds) and time-to-peak (TP) of 8.2 ± 0.7 seconds (1As: 10.3 ± 1 seconds and 3As:5.7 ± 0.5 seconds). No significant differences were detected for all parameters between 1As and 3As for KCl or Ado application, while 1As had a significantly longer TP and greater peak dilation than 3As to Ach. These findings demonstrate that 1As and 3As from the rat G muscle appear to have similar responsiveness to vasoactive agonists. Furthermore, the average TD before vasodilation supports a role for metabolic signals as contributors to the ROV. [source] Marvels, Mysteries, and Misconceptions of Vascular Compensation to Peripheral Artery OcclusionMICROCIRCULATION, Issue 1 2010MATTHEW A. ZIEGLER Microcirculation (2010) 17, 3,20. doi: 10.1111/j.1549-8719.2010.00008.x Abstract Peripheral arterial disease is a major health problem and there is a significant need to develop therapies to prevent its progression to claudication and critical limb ischemia. Promising results in rodent models of arterial occlusion have generally failed to predict clinical success and led to questions of their relevance. While sub-optimal models may have contributed to the lack of progress, we suggest that advancement has also been hindered by misconceptions of the human capacity for compensation and the specific vessels which are of primary importance. We present and summarize new and existing data from humans, Ossabaw miniature pigs, and rodents which provide compelling evidence that natural compensation to occlusion of a major artery (i) may completely restore perfusion, (ii) occurs in specific pre-existing small arteries, rather than the distal vasculature, via mechanisms involving flow-mediated dilation and remodeling (iii) is impaired by cardiovascular risk factors which suppress the flow-mediated mechanisms and (iv) can be restored by reversal of endothelial dysfunction. We propose that restoration of the capacity for flow-mediated dilation and remodeling in small arteries represents a largely unexplored potential therapeutic opportunity to enhance compensation for major arterial occlusion and prevent the progression to critical limb ischemia in the peripheral circulation. [source] Theoretical Modeling in Hemodynamics of MicrocirculationMICROCIRCULATION, Issue 8 2008JACK LEE ABSTRACT Over the past decades, theoretical modeling has become an indispensable component of research into the hemodynamics of microcirculation. Numerous studies rely on modeling to provide quantitative insights into the interacting biophysical mechanisms that govern microcirculatory flow. The mechanical deformation of hematocytes has been addressed by continuum and molecular-informed computational models based on a growing body of experimental information. Theoretical analyses of single-vessel flow and blood rheology have led to a range of modeling approaches. Until recently, computational constraints limited direct simulations of multi-particle flows involving deformation and/or aggregation, but recent studies have begun to address this challenge. Network-level analyses have provided insights into the biophysical principles underlying the design of the microcirculation. This approach has been used to complement available experimental data and to derive empirical models of microvascular blood rheology. Continued increases in computational performance applied to current modeling techniques will enable larger scale simulations. In order to exploit this opportunity, integration of diverse theoretical approaches within a multi-scale framework is needed. [source] Arteriolar Remodeling Following Ischemic Injury Extends from Capillary to Large Arteriole in the MicrocirculationMICROCIRCULATION, Issue 5 2008Alexander M. Bailey ABSTRACT Objective: Skeletal muscle vasculature undergoes arteriogenesis to restore tissue perfusion and function following loss of blood flow. This process has been shown to occur in large vessels following ischemia, although recent studies suggest this may occur in the microcirculation as well. We tested the hypothesis that ischemia induces microvascular remodeling in the skeletal muscle microcirculation on the scale of capillary to sub-35 ,m diameter arterioles. Methods: Ligations of a feeding arteriole to the caudal-half of the spinotrapezius muscle were performed on C57BL/6 mice. At 5 days, microvascular remodeling responses were quantified using intravital and whole-mount confocal microscopy. Immunohistochemistry was performed to visualize vessels, incorporated leukocytes, and regions of hypoxia. Results: Ischemic tissue underwent localized microvascular remodeling characteristic of arteriogenesis, including pronounced vessel tortuosity. In patent microvessels (diameters 15,35 ,m), we observed increases in vascular density (38%), branching (90%) and collateral development (36.5%). The formation of new arterioles (diameters 6,35 ,m) increased by 24.3%, while chronic hypoxia was absent from all tissues. Conclusions: Ischemic injury induces arteriogenesis in skeletal muscle microcirculation. Furthermore, this surgical model enables en face analysis of microcirculatory adaptations with single-cell resolution and can provide investigators with morphometric data on a microscale that is difficult to achieve using other models. [source] Inflammatory and Hemodynamic Changes in the Cerebral Microcirculation of Aged Rats after Global Cerebral Ischemia and ReperfusionMICROCIRCULATION, Issue 4 2008Leslie Ritter ABSTRACT Effects of aging on inflammation and blood flow in the brain are unclear. Young (three to six months) and aged (19,22 months) male Brown Norway Fisher rats were used to compare (i) leukocyte function in nonischemic conditions and (ii) leukocyte function and hemodynamic changes after ischemia-reperfusion (I-R). In nonischemic studies, polymorphonuclear (PMN) CD11b expression and reactive oxygen species (ROS) production were measured with flow cytometry and PMN chemotaxis was measured with a Boyden chamber (+/-fMLP). In I-R studies, ischemia was induced by bilateral carotid artery occlusion and hypotension (20 minutes). During early reperfusion (30 minutes), leukocyte adhesion and rolling and blood-shear rates were measured using fluorescence microscopy. During late reperfusion (48 hours), mortality, neurological function, and leukocyte infiltration were measured. Stimulated PMN chemotaxis was increased in nonischemic aged rats (p < 0.05). In early reperfusion, there was a significant increase in leukocyte rolling and adhesion in the cerebral microcirculation and a significant decrease in shear rate in aged rats, compared to the young (p < 0.05). During late reperfusion, neurologic function was worse in aged vs. young rats (p < 0.05). These findings suggest that increased intravascular PMN adhesion and vascular dysfunction may contribute to poor neurologic outcome after cerebral I-R in the aged brain. [source] Longitudinal and Radial Gradients of PO2 in the Hamster Cheek Pouch MicrocirculationMICROCIRCULATION, Issue 3 2008Helena Carvalho ABSTRACT Objectives: The aim of this study was to determine longitudinal and radial gradients in oxygen tension (PO2) in microvessels of the hamster cheek pouch. Methods: We measured PO2 using the phosphorescence-quenching method in two orders of arterioles (45.8 ± 5.5 and 19.9 ± 1.8 , m diameter), capillaries, and two orders of venules (50.5 ± 3.4 and 21.4 ± 2.0 , m diameter) in order to determine the longitudinal PO2 gradient. At the arteriolar and venular sites, we also measured PO2 at four different sites for an analysis of radial PO2 gradients: centerline, inside wall (larger arteriole and venule only), outside wall, and interstitium. We used 10 hamsters weighing 115 ± 27 g anesthetized with pentobarbital intraperitoneally and maintained with alpha-chloralose intravenously. The cheek pouch was everted and a single-layered preparation was studied by intravital microscopy. Albumin-bound Pd-porphyrin was infused into the circulation and excited by flash illumination at 10 Hz, with a rectangular diaphragm limiting the excitation field to 5 × 25 , m. Results: In the longitudinal direction, intravascular PO2 decreased significantly (P < 0.01) from large arterioles (39.5 ± 2.3 mmHg) to small arterioles (32.2 ± 0.3 mmHg), then to capillaries (30.2 ± 1.8 mmHg), and on to small venules (27.3 ± 2.1 mmHg) and large venules (25.5 ± 2.2 mmHg). In the radial direction, PO2 decreased significantly (P < 0.01) in and around larger arterioles, and to a lesser extent, around the smaller ones (P < 0.05). There was no significant PO2 gradient, longitudinal or radial, associated with venules. The PO2 difference from the centerline to the outside wall in large arterioles was 8.3 ± 1.4 mmHg, and most of the decline in PO2 in the radial direction was contributed by the intravascular difference (4.7 ± 2.1 mmHg) and only about 1.0 ± 2.7 mmHg by the transmural difference. Conclusions: Our data show that there are large intra-arteriolar radial PO2 gradients, but no large transmural PO2 differences, suggesting that the oxygen consumption of the microvessel wall is not exceptionally high. [source] Capillary Hemodynamics and Oxygen Pressures in the Aging MicrocirculationMICROCIRCULATION, Issue 4 2006DAVID C. POOLE ABSTRACT Healthy aging acts to redistribute blood flow (Q,) and thus O2 delivery (Q,O2) among and within the exercising muscles such that Q,O2 to highly oxidative muscle fibers may be compromised. Within the microcirculation of old muscles capillary hemodynamics are altered and the matching of Q,O2 to oxidative requirements (V,O2) is impaired such that at exercise onset the microvascular O2 pressure falls below that seen in their younger counterparts. This is important because the microvascular O2 pressure denotes the sole driving force for blood-myocyte O2 transfer and any compromise may slow V,O2 kinetics and reduce exercise tolerance. This review considers the microcirculatory evidence for a reduced perfusive (Q,O2) and diffusive O2 flux within aged muscle and highlights the pressing need for intravital microscopy studies of the muscle microcirculation during exercise. [source] A Computer-Based Method for Determination of the Cell-Free Layer Width in MicrocirculationMICROCIRCULATION, Issue 3 2006SANGHO KIM ABSTRACT Objectives: The cell-free layer between the erythrocyte column and the vessel wall is an important determinant of hydrodynamic resistance in microcirculatory vessels. The authors report a method for continuous measurement of the width of this layer. Methods: The light intensity of a linear array of pixels perpendicular to the vessel axis is continuously determined from a video image of a microcirculatory vessel. A threshold level based on Otsu's method is used to establish the interface between the cell-free layer and the erythrocyte column. To test the method, video images at 750,4500 frames/s were obtained from venules and arterioles in rat spinotrapezius muscle at normal and reduced arterial pressures before and after induction of erythrocyte aggregation with Dextran 500. The current measurements were compared to manual measurements of the same images. Results: Values obtained by the manual and the new methods were in agreement within the 95% confidence limit by the Bland-Altman analysis and within 90,95% range by the correlation coefficient (R2). The more frequent measurements reveal substantial, rapid variations in cell-free layer width and changes in mean values with alteration of arterial pressure and red cell aggregability. Conclusions: A new, computer-based technique has been developed that provides measurements of rapid, time-dependent variations in the width of the cell-free layer in the microcirculation. [source] Regulation of Blood Flow in the MicrocirculationMICROCIRCULATION, Issue 1 2005STEVEN S. SEGAL ABSTRACT The regulation of blood flow has rich history of investigation and is exemplified in exercising skeletal muscle by a concerted interaction between striated muscle fibers and their microvascular supply. This review considers blood flow control in light of the regulation of capillary perfusion by and among terminal arterioles, the distribution of blood flow in arteriolar networks according to metabolic and hemodynamic feedback from active muscle fibers, and the balance between peak muscle blood flow and arterial blood pressure by sympathetic nerve activity. As metabolic demand increases, the locus of regulating oxygen delivery to muscle fibers "ascends" from terminal arterioles, through intermediate distributing arterioles, and into the proximal arterioles and feed arteries, which govern total flow into a muscle. At multiple levels, venules are positioned to provide feedback to nearby arterioles regarding the metabolic state of the tissue through the convection and production of vasodilator stimuli. Electrical signals initiated on smooth muscle and endothelial cells can travel rapidly for millimeters through cell-to-cell conduction via gap junction channels, rapidly coordinating vasodilator responses that govern the distribution and magnitude of blood flow to active muscle fibers. Sympathetic constriction of proximal arterioles and feed arteries can restrict functional hyperemia while dilation prevails in distal arterioles to promote oxygen extraction. With vasomotor tone reflecting myogenic contraction of smooth muscle cells modulated by flow-induced vasodilator production by endothelium, the initiation of functional vasodilation and its modulation by shear stress and sympathetic innervation dictate how and where blood flow is distributed in microvascular networks. A remarkable ensemble of signaling pathways underlie the integration of smooth muscle and endothelial cell function in microvascular networks. These pathways are being defined with new insight as novel approaches are applied to understanding the cellular and molecular mechanisms of blood flow control. [source] Impairment of Hepatic Microcirculation in Fatty LiverMICROCIRCULATION, Issue 6 2003SAMIA IJAZ ABSTRACT Fatty liver or hepatic steatosis, which is the result of the abnormal accumulation of triacylglycerol within the cytoplasm of hepatocytes, is a common histological finding in human liver biopsy specimens that is attributed to the effects of alcohol excess, obesity, diabetes, or drugs. There is a general consensus that fatty liver compromises hepatic microcirculation, the common exchange network upon which hepatic arterial and portal inflows converge, regardless of underlying etiology. A significant reduction in hepatic microcirculation has been observed in human fatty donor livers and in experimental models of hepatic steatosis. There is an inverse correlation between the degree of fat infiltration and both total hepatic blood flow and flow in microcirculation. Fatty accumulation in the cytoplasm of the hepatocytes is associated with an increase in the cell volume that reduces the size of the hepatic sinusoid space by 50% compared with a normal liver and may result in partial or complete obstruction of the hepatic sinusoid space. As a result of impaired hepatic microcirculation, the hepatocytes of the fatty liver have reduced tolerance against ischemia-reperfusion injury, which affects about 25% of the donors for liver transplantation because severe steatosis is associated with a high risk of primary nonfunction after liver transplantation. [source] Application of Physiological Genomics to the MicrocirculationMICROCIRCULATION, Issue 1 2002Dr. Andrew S. Greene Physiological genomics represents a new challenge in the biological sciences,the quest to define the functions of thousands of genes that will emerge from the sequencing of the human genome and the genomes of other model organisms. Because the attention of the scientific community has focused on this task, new tools that will allow high-efficiency identification of gene function are being developed at remarkable speed. Physiological genomic approaches to understanding integrated systems function are now becoming widely used in many areas of biological research. The availability of genomic information across species has now revealed a striking degree of conservation of both gene order and function, allowing researchers to easily move from model organisms to man in the hunt for gene function. Physiological genomics approaches in the cardiovascular system have focused on disease-based models and the behavior of large vessels. In the microcirculation, genomic studies have largely been confined to the use of single gene knockouts or to the study of angiogenesis. This review summarizes the strategies for physiological genomics that are appropriate to the study of the microcirculation and discusses several key discoveries that have been made by using these approaches. [source] What's New in the Cerebral Microcirculation?MICROCIRCULATION, Issue 6 2001DONALD D. HEISTAD ABSTRACT The first part of this paper focuses on unusual aspects of the cerebral circulation. Cerebral vessels have less smooth muscle and adventitia than other vessels, and the endothelial blood-brain barrier is unique. Because the wall of the arteries is thin, one might expect that the vessels are especially vulnerable to rupture. Pressure in intracranial arteries, however, is lower than in other arteries, because resistance of larger cerebral arteries is remarkably high. The low pressure in cerebral arteries presumably protects against rupture of the vessels. The second part of the paper summarizes some new insights into regulation of cerebral circulation. One concept is that "breakthrough" of autoregulation, with dilatation of cerebral vessels at high levels of pressure, is an active process, rather than a passive phenomenon. This conclusion is based on the finding that inhibitors of calcium-dependent potassium channels greatly attenuate the cerebral vasodilator response during acute hypertension. The third part of the paper focuses on effects of gene transfer to cerebral blood vessels. Gene transfer to intracranial and extracranial vessels is feasible and vasomotor function can be altered. Gene transfer has proven to be useful to study vascular biology, and we are optimistic that the approach will ultimately lead to gene therapy. [source] Bimodal Oscillation Frequencies of Blood Flow in the Inflammatory Colon MicrocirculationTHE ANATOMICAL RECORD : ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY, Issue 1 2009Akira Tsuda Abstract Rhythmic changes in blood flow direction have been described in the mucosal plexus of mice with acute colitis. In this report, we studied mice with acute colitis induced either by dextran sodium sulfate or by trinitrobenzenesulfonic acid. Both forms of colitis were associated with blood flow oscillations as documented by fluorescence intravital videomicroscopy. The complex oscillation patterns suggested more than one mechanism for these changes in blood flow. By tracking fluorescent nanoparticles in the inflamed mucosal plexus, we identified two forms of blood flow oscillations within the inflammatory mouse colon. Stable oscillations were associated with a base frequency of approximately 2 cycles/sec. Velocity measurements in the upstream and downstream vessel segments indicated that stable oscillations were the result of regional flow occlusion within the mucosal plexus. In contrast, metastable oscillations demonstrated a lower frequency (0.2,0.4 cycles/sec) and appeared to be the result of flow dynamics in vessels linked by the bridging mucosal vessels. These blood flow oscillations were not directly associated with cardiopulmonary movement. We conclude that both the stable and metasable oscillating patterns reflect flow adaptations to inflammatory changes in the mucosal plexus. Anat Rec, 2009. © 2008 Wiley-Liss, Inc. [source] Resuscitating the Microcirculation in Sepsis: The Central Role of Nitric Oxide, Emerging Concepts for Novel Therapies, and Challenges for Clinical TrialsACADEMIC EMERGENCY MEDICINE, Issue 5 2008Stephen Trzeciak MD Abstract Microcirculatory dysfunction is a critical element of the pathogenesis of severe sepsis and septic shock. In this Bench-to-Bedside review, we present: 1) the central role of the microcirculation in the pathophysiology of sepsis; 2) new translational research techniques of in vivo video microscopy for assessment of microcirculatory flow in human subjects; 3) clinical investigations that reported associations between microcirculatory dysfunction and outcome in septic patients; 4) the potential role of novel agents to "rescue" the microcirculation in sepsis; 5) current challenges facing this emerging field of clinical investigation; and 6) a framework for the design of future clinical trials aimed to determine the impact of novel agents on microcirculatory flow and organ failure in patients with sepsis. We specifically focus this review on the central role and vital importance of the nitric oxide (NO) molecule in maintaining microcirculatory homeostasis and patency, especially when the microcirculation sustains an insult (as with sepsis). We also present the scientific rationale for clinical trials of exogenous NO administration to treat microcirculatory dysfunction and augment microcirculatory blood flow in early sepsis therapy. [source] Cerebral Thrombosis And Microcirculation Of The Rat During The Oestrous Cycle And After OvariectomyCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 1-2 2002H Ono SUMMARY 1. The effects of oestrogen on thrombogenesis and the cerebral microcirculation of the female rat were studied during the oestrous cycle and after ovariectomy. 2. Serum levels of oestradiol (E2) and plasma concentrations of nitric oxide (NO) metabolites were significantly greater at pro-oestrus than at dioestrus. Blood vessel diameter, mean red cell velocity, wall shear rate and blood flow at pro-oestrus were significantly higher than at dioestrus. Thrombotic tendency, assessed using a He,Ne laser-induced thrombosis model, was significantly decreased at pro-oestrus compared with dioestrus. 3. The long-term deprivation of oestrogen by ovariectomy significantly depressed serum levels of E2 and plasma concentrations of NO metabolites. Thrombotic tendency was significantly increased 4 weeks after ovariectomy. Vessel diameter, mean red cell velocity, wall shear rate and blood flow in pial arterioles were significantly reduced after ovariectomy. 4. Exogenous administration of oestrogen (17,-oestradiol) after surgery reversed the increased thrombotic tendency mediated by ovariectomy. 5. These results strongly indicate that oestrogen mediates beneficial effects on the cerebral microcirculation and moderates cerebral thrombotic mechanisms in the female rat. [source] Cross-talk between macro- and microcirculationACTA PHYSIOLOGICA, Issue 4 2010M. E. Safar Abstract Physiologically, macro- and microcirculation differ markedly as macrocirculation deals with pulsatile pressure and flow and microcirculation with steady pressure and flow. Various such haemodynamic aspects correspond to a large heterogeneity in the structure and function of the vascular tree. In the past, diseases such as hypertension and diabetes mellitus were classified on the basis of the structure and function of small and large arteries. The purpose of this paper is to review the cross-talk between the micro- and macrocirculation. We shall discuss this cross-talk from the perspective of the development, physiology and pathology of the entire arterial tree. [source] Slit-flow ektacytometry: Laser diffraction in a slit rheometerCYTOMETRY, Issue 1 2005Sehyun Shin Abstract Background Deformability of red blood cells (RBCs) is a determinant of blood flow resistance as RBCs pass through small capillaries of the microcirculation. Available techniques for measuring RBC deformability often require a washing process after each measurement, which is not optimal for day-to-day clinical use. Methods A laser diffraction technique has been combined with slit-flow rheometry, which shows significant advances in ektacytometric design, operation, and data analysis. The essential features of this design are its simplicity (ease of operation and no moving parts) and a disposable element that is in contact with the blood sample. Results With slit ektacytometry, the deformation of RBCs subjected to continuously decreasing shear stress in a slit flow can be quickly measured with extremely small quantities of blood. The measurements with the slit ektacytometer were compared with those of LORCA and a strong correlation was apparent. The deformability of the hardened RBCs was markedly lower than that of the normal RBCs. In addition, the young cells showed higher values of the elongation index than did the old cells. Conclusions The newly developed slit ektacytometer can measure RBC deformability with ease and accuracy. In addition, the slit ektacytometer can be easily used in a clinical setting owing to the incorporation of a disposable element that holds the blood sample. © 2005 Wiley-Liss, Inc. [source] The nervous system and gastrointestinal functionDEVELOPMENTAL DISABILITIES RESEARCH REVIEW, Issue 2 2008Muhammad A. Altaf Abstract The enteric nervous system is an integrative brain with collection of neurons in the gastrointestinal tract which is capable of functioning independently of the central nervous system (CNS). The enteric nervous system modulates motility, secretions, microcirculation, immune and inflammatory responses of the gastrointestinal tract. Dysphagia, feeding intolerance, gastroesophageal reflux, abdominal pain, and constipation are few of the medical problems frequently encountered in children with developmental disabilities. Alteration in bowel motility have been described in most of these disorders and can results from a primary defect in the enteric neurons or central modulation. The development and physiology of the enteric nervous system is discussed along with the basic mechanisms involved in controlling various functions of the gastrointestinal tract. The intestinal motility, neurogastric reflexes, and brain perception of visceral hyperalgesia are also discussed. This will help better understand the pathophysiology of these disorders in children with developmental disabilities. © 2008 Wiley-Liss, Inc. Dev Disabil Res Rev 2008;14:87,95. [source] Design of an Ultrasound Contrast Agent for Myocardial PerfusionECHOCARDIOGRAPHY, Issue 2000Michel Schneider Ph.D. Myocardial contrast echography (MCE) has been a major research objective in cardiovascular ultrasound for almost two decades. The design of a contrast agent fulfilling the needs of MCE requires taking into consideration a number of points: a basic decision has to be made whether a deposit agent or a free-flowing agent would be more appropriate and whether an agent active at low/medium mechanical index (MI) is preferable to an agent active only at high MI; only a small percentage of the cardiac output enters the coronary microcirculation, which means that highly sensitive bubble detection methods, such as harmonic imaging or pulse inversion, are needed; the low velocity of blood in the microcirculation that leads to extensive bubble destruction during imaging means that intermittent imaging and/or an agent active at low MI is (are) required; the duration of the contrast effect must be sufficient to allow a complete examination and is affected by the rate of contrast administration; the performance of the contrast agent should not be equipment-dependent. The ultimate goal in MCE is to be able to quantify blood flow in the various segments to determine if adequate oxygenation is achieved. Ultrasound-mediated bubble destruction followed by the measurement of bubble replenishment kinetics opens new perspectives for quantification. SonoVue is a free-flowing ultrasound contrast agent made of sulphur hexafluoride microbubbles stabilized by a highly elastic phospholipid monolayer. SonoVue is able to produce myocardial opacification at a wide range of acoustic pressures and in particular at Mis as low as 0.1. Its performance is not equipment-dependent. Good results for myocardial opacification have been observed in all animal species tested (dogs, minipigs, rabbits), using continuous as well as intermittent imaging. Trials are in progress to demonstrate the clinical utility of SonoVue for rest and stress perfusion studies, in particular for the diagnosis of CAD, the detection of myocardial infarction, the assessment of the success of interventions and myocardial viability, and the detection of hibernating myocardium. [source] The polysaccharide fucoidan inhibits microvascular thrombus formation independently from P- and l -selectin function in vivoEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 9 2000Thorlacius Background Adhesion molecules of the selectin family (mainly P- and L-selectin) have been suggested to mediate interactions between platelets, leukocytes and endothelial cells in thrombus formation. The polysaccharide fucoidan has anticoagulative properties, but is also able to bind and block the function of the selectins. Here, we investigated in vivo (i) if fucoidan can prevent microvascular thrombus formation, and (ii) whether this is potentially mediated by the inhibition of P-and/or L-selectin. Materials and Methods For this purpose, we used intravital microscopy in the mouse cremaster microcirculation in which thrombosis was induced photochemically by light exposure to individual arterioles and venules after intravenous (i.v.) injection of FITC-dextran. Results We found that intravenous administration of fucoidan significantly prolonged the time required for complete occlusion in arterioles and venules by almost seven- and nine-fold, respectively. In contrast, treatment with monoclonal antibodies against P- and L-selectin had no effect on the development of microvascular thrombosis. Fucoidan and also the anti-P-selectin antibody completely inhibited baseline venular leukocyte rolling in the cremaster muscle, indicating that these treatment regimes abolished P-selectin function. Importantly, fucoidan and the anti-P-selectin antibody had no effect on systemic platelet and leukocyte counts. On the other hand, we found that fucoidan treatment significantly altered coagulation parameters, including prothrombin time (Quick percentage), activated partial thromboplastin time (APTT) and thrombin clotting time (TCT), which may explain the potent in vivo anticoagulative effect of fucoidan observed here. Conclusions Taken together, our novel findings suggest that fucoidan effectively prevents microvascular thrombus formation induced by endothelial damage in arterioles and venules in vivo. This protective effect of fucoidan is not attributable to inhibition of P- and L -selectin function but may instead be related to the anticoagulative capacity of fucoidan. [source] Optical tweezers for measuring red blood cell elasticity: application to the study of drug response in sickle cell diseaseEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 4 2003M. M. Brandão Abstract: The deformability of erythrocytes is a critical determinant of blood flow in microcirculation. By capturing red blood cells (RBC) with optical tweezers and dragging them through a viscous fluid we were able to measure their overall elasticity. We measured, and compared, the RBC deformability of 15 homozygous patients (HbSS) including five patients taking hydroxyurea (HU) for at least 6 months (HbSS/HU), 10 subjects with sickle cell trait (HbAS) and 35 normal controls. Our results showed that the RBC deformability was significantly lower in haemoglobin S (HbS) subjects (HbSS and HbAS), except for HbSS/HU cells, whose deformability was similar to the normal controls. Our data showed that the laser optical tweezers technique is able to detect differences in HbS RBC from subjects taking HU, and to differentiate RBC from normal controls and HbAS, indicating that this is a very sensitive method and can be applied for detection of drug-response in sickle cell disease. 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