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CSF hydrodynamics in superior sagittal sinus thrombosis.

Cerebrospinal fluid hydrodynamics were investigated with a constant pressure infusion method in patients with superior sagittal sinus thrombosis. Ten patients were studied with serial examinations up to 15 years after the onset of the disease. A total of 70 CSF hydrodynamic examinations were performed. A clear increase in intracranial pressure due to raised pressure in the major dural sinus was seen in all patients. A striking feature was the persistent intracranial pressure increase that declined only gradually. This had no obvious clinical impact. Change in CSF resorption facility played only a minor role in the intracranial pressure elevation. None of the patients developed hydrocephalus.

Adolescent↗

Polymer collapse in the presence of hydrodynamic interactions.

We investigate numerically the dynamical behaviour of a polymer chain collapsing in a dilute solution. The rate of collapse is measured with and without the presence of hydrodynamic interactions. We find that hydrodynamic interactions both accelerate polymer collapse and alter the folding pathway.

Journal Article↗

Molecular-dynamics simulations with explicit hydrodynamics I: on the friction coefficients of deformed polymers.

We implement large-scale Molecular-Dynamics (MD) simulations which incorporate hydrodynamic interactions via the inclusion of explicit Lennard-Jones solvent to examine the behaviour of polymer chains in sieving media. We begin by examining the friction coefficients of polymers in long-lived states responsible for inducing length-dependent mobility, i.e., allowing separation of polymers (or polyelectrolytes) by molecular weight. In particular, the conformations we examine occur in devices which utilize arrays of molecular obstacles or dilute solutions of polymers. We compare the results from our MD simulations with expressions from macroscopic hydrodynamics for four specific cases: i) a random coil excluded-volume Zimm polymer, ii) a rigid polymer moving perpendicular to its major axis iii) a rigid polymer moving parallel to its major axis and iv) a rigid polymer, folded at different points along its contour. We also examine the behaviour of the friction coefficient of a fully flexible molecule pulled by its middle monomer as a function of an applied force F and show that there are several distinct frictional regimes.

Journal Article↗

Rapid thrombectomy with a hydrodynamic catheter: results from a prospective, multicenter trial.

PURPOSE: To evaluate efficacy and safety of a hydrodynamic rheolytic thrombectomy device for rapid percutaneous treatment of acute thromboembolic occlusions of native lower-extremity arteries and bypass grafts. MATERIALS AND METHODS: In 50 patients, thrombectomy was performed with the rheolytic catheter at four centers. Patients had acute occlusions of native lower-extremity arteries (n = 39) or acute thrombosis of lower-limb bypass grafts (n = 11). Estimated occlusion age was 5 days +/- 5. Mean thrombus length was 15 cm +/- 11. Clinical success was measured on a scale of -3 (deterioration) to +3 (improvement) with established criteria. RESULTS: With the thrombectomy catheter, the majority of thrombus material was removed and antegrade blood flow was reestablished in 45 (90%) patients. Technical success (residual luminal narrowing < 50%) was 52% with use of the device alone. Adjunctive therapy was performed in 45 patients. Clinical improvement after intervention was +3 in 25 (50%) patients, +2 in 10 (20%), +1 in six (12%), and 0 (no improvement) in nine (18%). Clinically unimportant complications related to use of the device were one (2%) distal embolization and two (4%) dissections. Laboratory analysis revealed hemolysis without clinical sequelae. Primary patency rates were 76% after 30 days, 74% after 3 months, and 69% after 1 year. CONCLUSION: The hydrodynamic catheter appears to be safe and effective for rapid thrombectomy.

Aged↗

In vitro effectiveness study of three hydrodynamic thrombectomy devices.

PURPOSE: To determine the in vitro efficacy of three hydrodynamic thrombectomy devices. MATERIALS AND METHODS: Thrombectomy of clots was performed with three thrombectomy devices (Angiojet [AJ], Possis Medical, Minneapolis, Minn; Hydrolyser [HL] Cordis Europe, Roden, the Netherlands; and the Shredding Embolectomy Thrombectomy [SET] catheter, HP-Medica, Augsburg, Germany) in a flow model. RESULTS: Mean thrombectomy time ranged from 10.22 seconds (HL) to 37.73 seconds (AJ with guide wire). For the AJ and HL, the use of guide wires prolonged thrombectomy time (P < .01). The AJ with and without a guide wire and the HL with a 0.018-inch guide wire worked isovolumetrically, whereas the mean ratio of applied saline and aspirated fluid for the other devices was different from 1, ranging from 0.54 to 0.72. Mean embolus weight with the AJ alone (56.44 mg) was significantly higher than that with the SET catheter alone (3.15 mg) and with a guide wire (1.31 mg, P < .01 for both) and the HL alone (3.9 mg, P < .05), as was the embolus weight with the HL with a 0.018-inch guide wire (66.5 mg) compared with the SET catheter with and without a guide wire (P < .01), AJ with a guide wire (22.33 mg, P < .05), the HL alone (P < .01), and the HL with a 0.025-inch guide wire (24.86 mg, P < .05). CONCLUSION: The devices showed performance differences. The SET catheter alone and with a guide wire and the HL may bear an increased risk of procedure-related anemia. In clinical applications, hydrodynamic thrombectomy might substantially reduce the need for thrombolytic therapy.

Equipment Design↗

Hydrodynamic thrombectomy system versus pulse-spray thrombolysis for thrombosed hemodialysis grafts: a multicenter prospective randomized comparison.

PURPOSE: To evaluate the safety and efficacy of a hydrodynamic thrombectomy system in a prospective, multicenter randomized comparison with pulse-spray thrombolysis in hemodialysis grafts. MATERIALS AND METHODS: Nine centers enrolled 120 adult patients with recently (</=14 days) thrombosed hemodialysis grafts. Graft venography was used to confirm occlusion in 62 patients randomly assigned to thrombectomy and 58 to thrombolysis. For thrombolysis, a mixture of 5,000 U of heparin and 250,000 U of urokinase was distributed throughout the thrombus, first to the venous then to the arterial graft end. For thrombectomy, the catheter was passed in the same sequence. Technical success was removal of 80% or more of thrombus. Clinical success was technical success plus the ability to dialyze. Also assessed were total procedure time, thrombus treatment time, procedure-related blood loss, other complications, and 30- and 90-day outcomes. RESULTS: Patient demographics were comparable. Technical success rates were 95% (59 of 62) for thrombectomy and 90% (52 of 58) for thrombolysis (P: =.31). Clinical success rates were 89% (55 of 62) and 81% (47 of 58), respectively (P: =.24). At 30 days, 69% (43 of 62) and 66% (38 of 58), respectively, could be dialyzed through the graft (P: =.70); at 90 days, the rates were 40% (25 of 62) and 41% (24 of 58), respectively (P: =.91). None of these differences or those for procedure-related blood loss and early and late complications were statistically significant. Thrombus treatment times of 16.8 minutes for thrombectomy and 23.4 minutes for thrombolysis were significantly different (P: <.01). CONCLUSION: The hydrodynamic thrombectomy system is at least as efficacious and safe as pulse-spray thrombolysis but shortens thrombus treatment time.

Adult↗

Isolated perfused Ambystoma proximal tubule: hydrodynamics modulates ultrastructure.

A method using a pressure-sensing servo-pipette is described for measuring downstream transepithelial pressure within isolated renal tubules perfused at flow rates designed to keep luminal solution composition constant. The hydrodynamics of in vitro microperfusion of isolated proximal tubules of Ambystoma tigrinum was varied and different states of transepithelial hydrostatic pressure difference, axial tubule flow, and transepithelial transport were correlated with epithelial ultrastructure. Tubules analyzed by ultrastructural morphometry were as follows: unperfused with and without ouabain, perfused single-end cannulated with and without ouabain, and perfused double-end cannulated tubules incubated in substrate Ringer. The results indicate that proximal tubule fine structure is well preserved for more than 3 h in unperfused and perfused tubules. Small transepithelial hydrostatic pressure gradients (less than 162 Pa) increase tubule diameters and decrease cell height without changing volumes of the cells, lateral intercellular spaces (LIS), or the basal extracellular labyrinth (BEL). Pressure gradients of 271 Pa have no further effect on tubule diameters or cell height, but significantly reduce volumes of LIS and BEL. Transport inhibition and axial flow changes have minor structural effects. This study demonstrates a close dependence of tubule ultrastructure on hydrodynamic conditions and provides guidelines for optimizing the latter during perfusion of isolated renal tubules.

Ambystoma↗

Altering hydrodynamic variables influences PGI2 production by isolated lungs and endothelial cells.

Because deformation of lung tissue stimulates prostaglandin synthesis, we wanted to investigate whether hydrodynamic forces would affect lung prostacyclin (PGI2) production. To test the hypothesis that lung prostacyclin synthesis was flow dependent, we examined lung prostacyclin production after flow alterations. Using a salt solution that contained either Ficoll or albumin as a perfusate, we changed the flow to half and to double the control flow. When flow was changed, lung prostacyclin production followed changes in flow and pressure drop. When flow was varied in lungs treated with indomethacin, prostacyclin production was too low to be measurable. Variations in pressure pulsatility at constant mean flow had no influence on lung prostacyclin production. Since vascular distension may also stimulate prostacyclin production, we increased venous pressure. An increase in venous pressure (from 2.1 to 4.8 mmHg) had no effect on prostacyclin production; a further increase in venous pressure (to 7.5 mmHg) initiated edema and caused a large increase in prostacyclin production. When we subjected monolayers of endothelial cells cultured in wells to defined shear rates, the prostacyclin concentration in the supernatant quickly increased to a maximum. The absence of further increase with greater shear may have reflected feedback control of prostacyclin synthesis. The results indicated that hydrodynamic disturbances affect endothelial cells and stimulate arachidonate metabolism. Lung prostacyclin production may be related to flow. However, this effect is small compared with the lung prostacyclin production during edema formation.

Animals↗

The capsular organ of Chelyosoma productum (Ascidiacea: Corellidae): a new tunicate hydrodynamic sense organ.

Chelyosoma has about 200 sense organs in the atrial wall of the branchial sac that show structural features suggestive of a role in hydrodynamic sensing. They consist of a fluid-filled capsule with an acellular diaphragm spanning an opening in the top. The floor of the capsule is a sensory macula, with 5-6 primary sensory neurons whose cilia project into the capsular cavity and whose axons go to the brain. Animals were tested for vibrational sensitivity using a loudspeaker probe. They responded by muscular contractions of the siphons and/or arrests of the branchial cilia, both of which caused changes in water flow velocity through the siphons, which were monitored non-invasively using a thermistor flow meter. The animals showed peak sensitivity at 240-260 Hz. Subsequent calibration of the loudspeaker probe indicated that the animals could detect 104 decibels re 1 microPa from a source 80 cm away. The majority of axons leaving the capsular organs go to the brain via the visceral nerve. Cutting this nerve abolished or greatly reduced responses. Electrophysiological recordings from the distal nerve stump showed bursts of electrical events following vibrational stimulation. No such records could be obtained from other major nerves and cutting them did not affect responsivity. Corella inflata, a close relative of Chelyosoma, lacks capsular organs and failed to show any responses when the source was more than 3.5 cm away. We conclude that Chelyosoma's vibration-sensing ability is due to its capsular organs and is adaptive in terms of detecting the movements of objects in the vicinity. The findings are discussed in relation to the evolution of hydrodynamic mechanoreceptors in tunicates, amphioxus and craniates.

Animals↗

Pseudotumor cerebri: disordered cerebrospinal fluid hydrodynamics with extra-axial CSF collections.

Pseudotumor cerebri is uncommon in the pediatric age group and presents with clinical characteristics different from the adult form. We report a 5-year-old boy who presented with--seemingly spontaneous--alternating subdural CSF collections before progressing to develop pseudotumor cerebri. To our knowledge, this is the first report of such a presentation. In the prepubertal pediatric age group, pseudotumor cerebri may be associated with multiple etiologic factors (more than in the adult population). The exact common mechanism behind such a disorder is not known. Pseudotumor cerebri may be a disorder of CSF hydrodynamics. It may also be linked to other disorders of CSF hydrodynamics, as in our case. The exact link and mechanistic differences between these apparently related disorders deserve further analysis and investigation, possibly through dynamic MRI techniques.

Cerebrospinal Fluid↗

Effect of hydrodynamics-based gene delivery of plasmid DNA encoding interleukin-1 receptor antagonist-Ig for treatment of rat autoimmune myocarditis: possible mechanism for lymphocytes and noncardiac cells.

BACKGROUND: Interleukin-1 (IL-1) is a powerful and important cytokine in myocarditis. The purpose of this study was to evaluate the effect and possible mechanism of hydrodynamics-based delivery of the IL-1 receptor antagonist (IL-1RA)-immunoglobulin (Ig) gene for treatment of rat experimental autoimmune myocarditis (EAM). METHODS AND RESULTS: On the day after immunization, rats were transfected with either pCAGGS encoding IL-1RA-Ig or pCAGGS encoding Ig alone. On day 17, IL-1RA-Ig gene therapy was effective in controlling EAM, as monitored by a decreased ratio of heart weight to body weight, reduced myocarditis areas, reduced gene expression of atrial natriuretic peptide in hearts, and improved cardiac function in echocardiographic and hemodynamic parameters. Examination of the expression of IL-1-related genes in purified cells from EAM hearts suggested that ectopic IL-1RA-Ig-acting target cells were alphabetaT cells and noncardiomyocytic noninflammatory cells such as fibroblasts, smooth muscle cells, and endothelial cells. Therefore, we examined the effect of serum containing IL-1RA-Ig on the expression of immune-relevant genes within noncardiomyocytic cells cultured from EAM hearts or concanavalin A-stimulated lymphocytes derived from lymph nodes in EAM-affected rats. The expression of immunologic molecules (prostaglandin E synthase, cyclooxygenase-2, and IL-1beta) in cultivated noncardiomyocytic cells and Th1 cytokines (IL-2 and IFN-gamma) in lymphocytes was significantly decreased by the serum containing IL-1RA-Ig. CONCLUSIONS: EAM was suppressed by hydrodynamics-based delivery of plasmid DNA encoding IL-1RA-Ig. In addition, IL-1RA-Ig suppressed gene expression of prostaglandin synthases and IL-1 in noncardiomyocytic cells and Th1 cytokines in lymphocytes.

Animals↗

Hydrodynamic radii versus molecular weights in clearance studies of urine and cerebrospinal fluid.

The protein permeabilities of the blood-cerebrospinal-fluid barrier and the blood-urine barrier are compared. In both instances the permeation rates of proteins can be better correlated to hydrodynamic radii than to molecular weights. The decreasing clearance rates of ceruloplasmin, IgG, and IgA reflect the hydrodynamic heterogeneity of these proteins, which have similar weights. The IgM clearance rate appears too high, possibly owing to monomer IgM, other IgM fragments, selective transport, or active immunity, so its inclusion is not recommended in clearance studies.

Ceruloplasmin↗

Aspects of hydrodynamic shear regulating shear-induced platelet activation and self-association of von Willebrand factor in suspension.

The binding of plasma von Willebrand factor (VWF) to platelet receptor GpIb under high hydrodynamic shear leads to platelet activation and subsequent shear-induced platelet aggregation (SIPA). We quantitatively examined the aspects of fluid flow that regulate platelet activation by subjecting human blood and isolated platelets to well-defined shear conditions in a cone-plate viscometer. We made the following observations. First, Annexin V binding to phosphatidyl serine expressed on activated cells was detectable within 10 seconds of shear application. Second, fluid shear stress rather than shear rate controls platelet activation, and a threshold shear stress of approximately 80 dyn/cm(2) is necessary to induce significant activation. Under these conditions, individual domains of soluble VWF and platelet GpIb are subjected to similar magnitudes of fluid forces on the order of 0.1 pN, whereas GpIb with bound VWF is subjected to 1 pN. Third, cell-cell collisions and time-varying stresses are not essential for platelet activation. Fourth, the mechanism of platelet activation can be resolved in 2 steps based on the contribution of VWF and fluid forces. Fluid shear and VWF are required during the first step, when GpIb-VWF binding likely occurs. Subsequently, high shear forces alone in the absence of VWF in suspension can induce platelet activation. In other experiments, purified VWF was subjected to shear in the viscometer, and VWF morphology was assessed using light scattering. These studies demonstrate, for the first time, the ability of hydrodynamic forces to induce VWF aggregation in suspension. This VWF self-association may be an additional feature involved in controlling cell adhesion rates in circulation.

Annexin A5↗

Hydrodynamic guiding for addressing subsets of immobilized cells and molecules in microfluidic systems.

BACKGROUND: The interest in microfluidics and surface patterning is increasing as the use of these technologies in diverse biomedical applications is substantiated. Controlled molecular and cellular surface patterning is a costly and time-consuming process. Methods for keeping multiple separate experimental conditions on a patterned area are, therefore, needed to amplify the amount of biological information that can be retrieved from a patterned surface area. We describe, in three examples of biomedical applications, how this can be achieved in an open microfluidic system, by hydrodynamically guiding sample fluid over biological molecules and living cells immobilized on a surface. RESULTS: A microfluidic format of a standard assay for cell-membrane integrity showed a fast and dose-dependent toxicity of saponin on mammalian cells. A model of the interactions of human mononuclear leukocytes and endothelial cells was established. By contrast to static adhesion assays, cell-cell adhesion in this dynamic model depended on cytokine-mediated activation of both endothelial and blood cells. The microfluidic system allowed the use of unprocessed blood as sample material, and a specific and fast immunoassay for measuring the concentration of C-reactive protein in whole blood was demonstrated. CONCLUSION: The use of hydrodynamic guiding made multiple and dynamic experimental conditions on a small surface area possible. The ability to change the direction of flow and produce two-dimensional grids can increase the number of reactions per surface area even further. The described microfluidic system is widely applicable, and can take advantage of surfaces produced by current and future techniques for patterning in the micro- and nanometer scale.

Animals↗

The hydrodynamics of dolphin drafting.

BACKGROUND: Drafting in cetaceans is defined as the transfer of forces between individuals without actual physical contact between them. This behavior has long been surmised to explain how young dolphin calves keep up with their rapidly moving mothers. It has recently been observed that a significant number of calves become permanently separated from their mothers during chases by tuna vessels. A study of the hydrodynamics of drafting, initiated in the hope of understanding the mechanisms causing the separation of mothers and calves during fishing-related activities, is reported here. RESULTS: Quantitative results are shown for the forces and moments around a pair of unequally sized dolphin-like slender bodies. These include two major effects. First, the so-called Bernoulli suction, which stems from the fact that the local pressure drops in areas of high speed, results in an attractive force between mother and calf. Second is the displacement effect, in which the motion of the mother causes the water in front to move forwards and radially outwards, and water behind the body to move forwards to replace the animal's mass. Thus, the calf can gain a 'free ride' in the forward-moving areas. Utilizing these effects, the neonate can gain up to 90% of the thrust needed to move alongside the mother at speeds of up to 2.4 m/sec. A comparison with observations of eastern spinner dolphins (Stenella longirostris) is presented, showing savings of up to 60% in the thrust that calves require if they are to keep up with their mothers. CONCLUSIONS: A theoretical analysis, backed by observations of free-swimming dolphin schools, indicates that hydrodynamic interactions with mothers play an important role in enabling dolphin calves to keep up with rapidly moving adult school members.

Animals↗

In vitro hydrodynamics of the Embol-X cannula.

BACKGROUND: Prevention of intraoperative plaque dislodgement in patients with atherosclerotic ascending aorta by development of innovative aortic cannula designs gains growing interest in cardiac surgery. To increase knowledge about the hydrodynamics of the innovative Embol-X cannula, which includes an intra-aortic filter device targeting at atheromatous emboli capture, was the aim of the present study. METHODS: Pressure gradients and back pressures of the Embol-X cannula were measured at varying flow rates in a mock circulation and compared with two commonly used single-stream cannulae. RESULTS: At a flow rate of 5.5 l/min, pressure gradients across the Argyle and the RMI cannulae were 48% and 62% and back pressures 25% and 47% lower than the corresponding values across the Embol-X cannula. CONCLUSIONS: The novel concept of integrating a filter device may provide clinical advantages concerning neurologic outcome. Further in vivo studies seem to be desirable to obtain more information concerning the clinical effects of the Embol-X cannula hydrodynamics.

Cardiac Surgical Procedures↗

Improved hydrodynamics of a new aortic cannula with a novel tip design.

BACKGROUND: Reduction of atheroembolic complications during cardiopulmonary bypass remains a major challenge in cardiac surgery. New cannula tip designs may help to attenuate this problem by improved hydrodynamics. METHODS: Pressure gradients and back pressures of a new aortic cannula tip design were measured and compared with the Medos X-Flow, Sarns Soft-Flow and Argyle THI cannulae at various flow rates in a mock circulation followed by flow visualization. RESULTS: Pressure gradients were the lowest for the new cannula. Back pressures of the new cannula were up to 84% lower than for the Argyle cannula. The back pressure profile and flow visualization of the new cannula showed broad centric flow dispersion with a transcannula increase of flow area from 38 mm2 to 139 mm2. CONCLUSIONS: The new design of an aortic cannula tip provides improved hydrodynamics, with low pressure gradients, low back pressures and a uniform central dispersion of flow, reducing the sandblasting effect.

Aorta↗

Simulating the hydrodynamic conditions in the United States Pharmacopeia paddle dissolution apparatus.

The objective of this work was to examine the feasibility of developing a high-performance computing software system to simulate the United States Pharmacopeia (USP) dissolution apparatus 2 (paddle apparatus) and thus aid in characterizing the fluid hydrodynamics in the method. The USP apparatus was modeled using the hydrodynamic package Fluent. The Gambit program was used to create a "wireframe" of the apparatus and generate the 3-dimensional grids for the computational fluid dynamics solver. The Fluent solver was run on an IBM RS/6000 SP distributed memory parallel processor system, using 8 processors. Configurations with and without a tablet present were developed and examined. Simulations for a liquid-filled vessel at a paddle speed of 50 rpm were generated. Large variations in fluid velocity magnitudes with position in the vessel were evident. Fluid velocity predictions were in good agreement with those previously published, using laser Doppler velocity measurements. A low-velocity domain was evident directly below the center of the rotating paddle. The model was extended to simulate the impact of the presence of a cylindrical tablet in the base of the dissolution vessel. The presence of the tablet complicated the local fluid flow, and large fluid shear rates were evident at the base of the compact. Fluid shear rates varied depending on the tablet surface and the location on the surface and were consistent with the reported asymmetrical dissolution of model tablets. The approach has the potential to explain the variable dissolution results reported and to aid in the design/prediction of optimal dissolution conditions for in vitro--in vivo correlations.

Chemistry, Pharmaceutical↗