Showing papers on "Pulsatile flow published in 2005"

Three-dimensional instabilities and transition of steady and pulsatile axisymmetric stenotic flows

Abstract: A straight tube with a smooth axisymmetric constriction is an idealized representation of a stenosed artery. We examine the three-dimensional instabilities and transition to turbulence of steady flow, steady flow plus an oscillatory component, and an idealized vascular pulsatile flow in a tube with a smooth 75 % stenosis using both linear stability analysis and direct numerical simulation. Steady flow undergoes a weak Coanda-type wall attachment and turbulent transition through a subcritical bifurcation, leading to hysteretic behaviour with respect to changes in Reynolds number. The pulsatile flows become unstable through a subcritical period-doubling bifurcation involving alternating tilting of the vortex rings that are ejected from the throat with each pulse. These tilted vortex rings rapidly break down through a self-induction mechanism within the confines of the tube. While the linear instability modes for pulsatile flow have maximum energy well downstream of the stenosis, we have established using direct numerical simulation that breakdown can gradually propagate upstream until it occurs within a few tube diameters of the constriction, in agreement with previous experimental observations. At the Reynolds numbers employed in the present study, transition is localized, with relaminarization occurring further downstream. A non-exhaustive investigation has also been undertaken into the receptivity of the axisymmetric shear layer in the idealized physiological pulsatile flow, with the results suggesting it has localized convective instability over part of the pulse cycle.

Quantifying the effect of posture on intracranial physiology in humans by MRI flow studies.

Abstract: Purpose: To quantify the effect of posture on intracranial physiology in humans by MRI, and demonstrate the relationship between intracranial compliance (ICC) and pressure (ICP), and the pulsatility of blood and CSF flows. Materials and Methods: Ten healthy volunteers (29 7 years old) were scanned in the supine and sitting positions using a vertical gap MRI scanner. Pulsatile blood and CSF flows into and out from the brain were visualized and quantified using time-of-flight (TOF) and cine phase-contrast techniques, respectively. The total cerebral blood flow (tCBF), venous outflow, ICC, and ICP for the two postures were then calculated from the arterial, venous, and CSF volumetric flow rate waveforms using a previously described method. Results: In the upright posture, venous outflow is considerably less pulsatile (57%) and occurs predominantly through the vertebral plexus, while in the supine posture venous outflow occurs predominantly through the internal jugular veins. A slightly lower tCBF (12%), a considerably smaller CSF volume oscillating between the cranium and the spinal canal (48%), and a much larger ICC (2.8-fold) with a corresponding decrease in the MRI-derived ICP values were measured in the sitting position. Conclusion: The effect of posture on intracranial physiology can be quantified by MRI because posture-related changes in ICC and ICP strongly affect the dynamics of cerebral blood and CSF flows. This study provides important insight into the coupling that exists between arterial, venous, and CSF flow dynamics, and how it is affected by posture.

Pulsatile cerebrospinal fluid dynamics in the human brain

Abstract: Disturbances of the cerebrospinal fluid (CSF) flow in the brain can lead to hydrocephalus, a condition affecting thousands of people annually in the US. Considerable controversy exists about fluid and pressure dynamics, and about how the brain responds to changes in flow patterns and compression in hydrocephalus. This paper presents a new model based on the first principles of fluid mechanics. This model of fluid-structure interactions predicts flows and pressures throughout the brain's ventricular pathways consistent with both animal intracranial pressure (ICP) measurements and human CINE phase-contrast magnetic resonance imaging data. The computations provide approximations of the tissue deformations of the brain parenchyma. The model also quantifies the pulsatile CSF motion including flow reversal in the aqueduct as well as the changes in ICPs due to brain tissue compression. It does not require the existence of large transmural pressure differences as the force for ventricular expansion. Finally, the new model gives an explanation of communicating hydrocephalus and the phenomenon of asymmetric hydrocephalus.

Effects of Flow Patterns on the Localization and Expression of VE-Cadherin at Vascular Endothelial Cell Junctions: In vivo and in vitro Investigations

Abstract: Atherosclerosis occurs preferentially at vascular curvature and branch sites where the vessel walls are exposed to fluctuating shear stress and have high endothelial permeability. Endothelial permeability is modulated by intercellular adhesion molecules such as VE-cadherin. This study was designed to elucidate the effects of different flow patterns on the localization and expression of VE-cadherin in endothelial cells (ECs) both in vivo and in vitro. VE-cadherin staining at EC borders was much stronger in the descending thoracic aorta and abdominal aorta, where the pulsatile flow has a strong net forward component than in the aortic arch and the poststenotic dilatation site beyond an experimental constriction, where the flow near the wall is complex and reciprocating with little net flow. With the use of flow chambers the effects of pulsatile flow (12 +/- 4 dyn/cm2 at 1 Hz) and reciprocating flow (0.5 +/- 4 dyn/cm2 at 1 Hz) on VE-cadherin organization in endothelial monolayers were studied in vitro. VE-cadherin staining was continuous along cell borders in static controls. Following 6 h of either pulsatile or reciprocating flow, the VE-cadherin staining at cell borders became intermittent. When the pulsatile flow was extended to 24, 48 or 72 h the staining around the cell borders became continuous again, but the staining was still intermittent when the reciprocating flow was similarly extended. Exposure to pulsatile or reciprocating flow for 6 and 24 h neither change the expression level of VE-cadherin nor its distribution between membrane and cytosol fractions as determined by Western blot and compared with static controls. These findings suggest that the cell junction remodeling induced by different flow patterns may result from a redistribution of VE-cadherin within the cell membrane. Both the in vivo and in vitro data indicate that pulsatile and reciprocating flow patterns have different effects on cell junction remodeling. The lack of junction reorganization in regions of reciprocating flow in vivo and in vitro may provide a mechanistic basis for the high permeability and the preferential localization of atherosclerosis in regions of the arterial stress with complex flow patterns and fluctuating shear stress.

Cellular and hemodynamics responses of failing myocardium to continuous flow mechanical circulatory support using the DeBakey-Noon left ventricular assist device: a comparative analysis with pulsatile-type devices.

Abstract: Background An increasing number of continuous flow pumps are currently under clinical studies, however very little data exist on the hemodynamic and cellular responses of the failing heart to continuous flow support. The purpose of this investigation was to characterize the response of the failing myocardium to continuous flow support. Methods We compared echocardiographic and cellular markers of failing myocardium at the time of left ventricular assist device (LVAD) implantation and explantation in 20 consecutive patients (12 pulsatile flow [Novacor] and 8 continuous flow [DeBakey-Noon]). Results The use of mechanical support with both continuous- or pulsatile-type LVADs resulted in a reduction of left ventricular end-diastolic dimension (LVEDD), end-diastolic volume (EDV), end-systolic volume (ESV) and left atrial volume (LAV), as well as a decrease in mitral E/A ratio, tricuspid regurgitation velocity (TRV) and pulmonary valve acceleration time (PVAT). Comparative analyses for patients treated with a continuous- vs pulsatile-type LVAD support showed a greater degree of unloading with the latter type, as shown by the effect on LVEDD (−13.7% vs −33.7%, p = 0.0.004), EDV (−23.5% vs −41.2%, p = 0.015), ESV (−25.6% vs −57.6%, p = 0.001) and LAV (−25.2% vs −40.4%, p = 0.071). The hemodynamic effects of continuous vs pulsatile LVAD support were similar, as shown by their effect on mitral E/A ratio (−23.9% vs −39.9%, p = NS), TRV (−26.4% vs −23.8%, p = NS) and PVAT (28.5% vs 38.5%, p = NS). Only pulsatile support demonstrated a statistically significant percent change in mass (−6.3% vs −20.6%, p = 0.038). Continuous and pulsatile forms of mechanical support demonstrated equivalent reductions in myocardial tumor necrosis factor-α (TNF-α), total collagen and mycocyte size. Conclusions Our findings show that, although there are differences between these 2 devices in magnitude of unloading, both forms of support effectively normalize cellular markers of the failing phenotype.

Reference ranges for umbilical vein blood flow in the second half of pregnancy based on longitudinal data

Abstract: Objectives To construct new reference ranges for serial measurements of umbilical vein (UV) blood flow. Methods Prospective longitudinal study of blood flow velocities and diameter of the UV measured at four-weekly intervals during 19 to 42 weeks' gestation in 130 low-risk singleton pregnancies. Regression models and multilevel modeling were used to construct the reference ranges. Results On the basis of 511 sets of longitudinal observations, we established new reference percentiles of UV diameter, blood flow velocities, volume flow, and blood flow normalized for fetal weight and abdominal circumference. They reflected some of the developmental patterns of previous cross-sectional studies, but with important differences, particularly near term. The UV blood flow showed a continuous increase until term, whereas the flow normalized per unit fetal weight, a corresponding reduction. Calculating the blood flow on the basis of intensity-weighted mean velocity or 0.5 of the maximum velocity gave almost interchangeable results for most fetuses. Conclusion New reference ranges for UV blood flow based on longitudinal observations appear slightly different from cross-sectional studies, and should be more appropriate for serial evaluation of fetal circulation. Copyright © 2005 John Wiley & Sons, Ltd.

The effect of LVAD aortic outflow-graft placement on hemodynamics and flow: Implantation technique and computer flow modeling.

Abstract: Axial-flow ventricular assist devices (VADs) can be implanted either through a left thoracotomy with outflow-graft anastomosis to the descending thoracic aorta or through a midline sternotomy with anastomosis to the ascending aorta. Each method has advantages and disadvantages. Because these VADs produce nonpulsatile flow, their hemodynamic characteristics differ from those of pulsatile devices. These differences may have important clinical consequences, particularly in relation to the outflow-graft configuration. We describe a computer-generated flow model that we created to illustrate the flow dynamics and possible clinical consequences of each method. The simulations indicate that the location of the anastomosis has important qualitative effects on flow in the ascending aorta and aortic arch. At high VAD outputs (≥75%), native cardiac output cannot supply the carotid and subclavian arteries. With a descending aortic anastomosis, net backward flow occurs in the descending aorta to supply these branches. Consequently, the aortic arch has a region with almost no net flow, where fluid particles stagnate over many cardiac cycles, possibly causing thrombogenesis. With an ascending aortic anastomosis, the arch has no stagnant region, although flow turbulence still occurs. When the aortic valve remains closed, so that the total output occurs through the VAD, the aortic root has a region of nearly stagnant flow. With an ascending aortic anastomosis, a small degree of recirculatory flow may prevent complete stagnation at the aortic root. With the descending aortic anastomosis, however, no recirculation occurs. These results help delineate the complex flow dynamics and the advantages and drawbacks of each technique.

Viscoelasticity of pediatric blood and its implications for the testing of a pulsatile pediatric blood pump.

Abstract: Red blood cell hematocrit, aggregation and deformability, and plasma protein concentration influence the viscosity and elasticity of whole blood. These parameters affect the flow properties, especially at low shear rates (< 50 s ‐1 ). In particular, we have previously shown that the viscoelasticity of fluid affects the inlet filling characteristics and regions of flow separation in small pulsatile blood pumps. Although the viscosity of pediatric blood has been thoroughly studied, its elasticity has not been previously measured. Here we present the viscosity and elasticity of pediatric blood against shear rate for hematocrits from 19‐56, measured using an oscillatory rheometer. There is little effect of patient age on blood viscoelasticity. A statistical analysis showed that when compared at constant hematocrit, blood from adult and pediatric patients had similar viscoelastic properties. We present blood analog solutions, as a function of hematocrit, constructed on the basis of the pediatric measurements. Flow field results for viscoelastic analogs of 20, 40 and 60% hematocrit and a Newtonian analog will be compared in the initial, in vitro testing of the Penn State pediatric blood pump, to determine the importance of incorporating a viscoelastic analog into the desigh interaction. ASAIO Journal 2005; 51:563‐566.

Anisotropic adaptive finite element method for modelling blood flow.

Abstract: In this study, we present an adaptive anisotropic finite element method (FEM) and demonstrate how computational efficiency can be increased when applying the method to the simulation of blood flow in the cardiovascular system. We use the SUPG formulation for the transient 3D incompressible Navier–Stokes equations which are discretised by linear finite elements for both the pressure and the velocity field. Given the pulsatile nature of the flow in blood vessels we have pursued adaptivity based on the average flow over a cardiac cycle. Error indicators are derived to define an anisotropic mesh metric field. Mesh modification algorithms are used to anisotropically adapt the mesh according to the desired size field. We demonstrate the efficiency of the method by first applying it to pulsatile flow in a straight cylindrical vessel and then to a porcine aorta with a stenosis bypassed by a graft. We demonstrate that the use of an anisotropic adaptive FEM can result in an order of magnitude reduction in computin...

The effects of pulsatile flow upon renal tissue perfusion during cardiopulmonary bypass: a comparative study of pulsatile and nonpulsatile flow.

Abstract: This study was conducted to directly compare the effects of pulsatile and nonpulsatile blood flow in the extracorporeal circulation upon renal tissue perfusion by using a tissue perfusion measurement system. A total cardiopulmonary bypass circuit was constructed to accommodate twelve Yorkshire swine, weighing 20 approximately 30 kg. Animals were randomly assigned to group 1 (n = 6, nonpulsatile centrifugal pump) or group 2 (n = 6, pulsatile T-PLS pump). A tissue perfusion measurement probe (Q-Flow 500) was inserted into the renal parenchymal tissue, and the extracorporeal circulation was maintained for an hour at a pump flow rate of 2 L/min after aortic cross-clamping. Tissue perfusion flow in the kidney was measured before bypass and every 10 minutes after bypass. Renal tissue perfusion flow was substantially higher in the pulsatile group throughout bypass (ranging 48.5-64.1 ml/min/100 g in group 1 vs. 51.0-88.1 ml/min/100 g in group 2). The intergroup difference was significant at 30 minutes (47.5 +/- 18.3 ml/min/100 g in group 1 vs. 83.4 +/- 28.5 ml/min/100 g in group 2; p = 0.026). Pulsatile flow achieves higher levels of tissue perfusion of the kidney during short-term extracorporeal circulation. A further study is required to observe the effects of pulsatile flow upon other vital organs and its long-term significance.

Cells in fluidic environments are sensitive to flow frequency

Abstract: Virtually all cells accommodate to their mechanical environment. In particular, cells subject to flow respond to rapid changes in fluid shear stress (SS), cyclic stretch (CS), and pressure. Recent studies have focused on the effect of pulsatility on cellular behavior. Since cells of many different tissue beds are constantly exposed to fluid flows over a narrow range of frequencies, we hypothesized that an intrinsic flow frequency that is optimal for determining cell phenotype exists. We report here that cells from various tissue beds (bovine aortic endothelial cells (BAEC), rat small intestine epithelial cells (RSIEC), and rat lung epithelial cells (RLEC)) proliferate maximally when cultured in a perfusion bioreactor under pulsatile conditions at a specific frequency, independent of the applied SS. Vascular endothelial and pulmonary epithelial cell proliferation peaked under 1 Hz pulsatile flow. In contrast, proliferation of gastrointestinal cells, which in their physiological context are subject to no flow or higher wavelength signal, was maximum at 0.125 Hz or under no flow. Moreover, exposure of BAEC to pulsatile flow of varying frequency influenced their nitric oxide synthase activity and prostacyclin production, which reached maximum values at 1 Hz. Notably, the "optimal" frequencies for the cell types examined correspond to the physiologic operating range of the organs from where they were initially derived. These findings suggest that frequency, independent of shear, is an essential determinant of cell response in pulsatile environments.

Chronic glucocorticoid treatment alters spontaneous pulsatile parathyroid hormone secretory dynamics in human subjects

Abstract: Objective: Spontaneous parathyroid hormone (PTH) secretory dynamics include tonic and pulsatile components. It is not known how glucocorticoids might alter these secretory dynamics. Design: The aim of our study was to evaluate spontaneous fluctuations in serum PTH levels in six adult male patients (aged 31 ‐ 64 years) receiving chronic ( . 6 months) therapy with glucocorticoids (daily dosage . 7.5 mg of prednisone or dose equivalent of other corticosteroid) as compared with a control group of 10 age- and sex-matched normal subjects. Methods: Peripheral venous blood sampling was performed every 3 min for 6 h from 0900 to 1500 h. Plasma PTH release profiles were subjected to deconvolution analysis, a method that resolves measured hormone concentrations into secretion and clearance components, and to an approximate entropy (ApEn) estimate, that in turn provides an integrated measure of the serial regularity or orderliness of the release process. Results: In the glucocorticoid-treated group, the PTH tonic secretory rate was reduced (4.3^0.74 vs 8.8^1.4 pg/ml per min in controls, P ¼ 0.017). There was, however, an increase in the fractional pulsatile PTH secretion (42^8.2 vs 18.3^3.9 pg/ml per min, P ¼ 0.006) in glucocorticoid-treated vs normal subjects. Mean overall PTH concentration, as well as mean integrated area, was similar among normal and glucocorticoid-treated subjects. Conclusions: These results demonstrate, for the first time, that chronic glucocorticoid treatment induces a redistribution of spontaneous PTH secretory dynamics by reducing the amount released in tonic fashion and increasing the amount released as pulses.

Effects of pulsatile CPB on interleukin-8 and endothelin-1 levels.

Abstract: Studies on pulsatile and nonpulsatile perfusion have long been performed. However, investigators have not reached a conclusion on which is more effective. In the present study, pulsatile cardiopulmonary bypass (CPB) was investigated in terms of the effects on cytokines, endothelin, catecholamine, and pulmonary and renal functions. Twenty-four patients who underwent coronary artery bypass grafting were divided into a pulsatile CPB group and a nonpulsatile CPB group. Parameters examined were hemodynamics, interleukin-8 (IL-8), endothelin-1 (ET-1), epinephrine, norepinephrine, lactate, arterial ketone body ratio, urine volume, blood urea nitrogen, creatinine, renin activity, angiotensin-II, lactate dehydrogenase, plasma-free hemoglobin, tracheal intubation time, and respiratory index. The IL-8 at 0.5, 3, and 6 h after CPB, and ET-1 at 3, 6, 9, and 18 h after CPB were significantly lower in the pulsatile group. Both epinephrine and norepinephrine were significantly lower in the pulsatile group. The respiratory index was significantly higher in the pulsatile group. In the present study, inhibitory effects on cytokine activity, edema in pulmonary alveoli, and endothelial damage were shown in addition to the favorable effects on catecholamine level, renal function, and peripheral circulation that have already been documented.

Major factors in the controversy of pulsatile versus nonpulsatile flow during acute and chronic cardiac support.

Abstract: During the past 50 years, the controversy over the benefits of pulsatile versus nonpulsatile flow in cardiac surgery has not been solved.1 A detailed investigation in all published literature reveals that in a majority of publications, the investigators could not show any differences between perfusion modes during acute or chronic cardiac support. However, in more than 20 articles, it appears clear that pulsatile flow causes significantly less vital organ injury and systemic inflammation during cardiopulmonary bypass (CPB) procedures and chronic cardiac circulatory support.1–23 To the best of our knowledge, there is not a single publication that clearly shows the benefits of nonpulsatile perfusion over pulsatile perfusion in acute or chronic clinical or animal settings. The pro-nonpulsatile flow investigators can only claim that there is no difference between perfusion modes, whereas the pro-pulsatile investigators have documented clear benefits.1–23 The objective of this editorial is to examine the major causes for this continuing controversy and suggest potential solutions to end it. Following are the two major causes for the controversy, and both are valid for acute or chronic settings.

Precise quantification of pressure flow waveforms of a pulsatile ventricular assist device.

Abstract: Unreliable quantification of flow pulsatility has hampered many efforts to assess the importance of pulsatile perfusion Generation of pulsatile flow depends upon an energy gradient It is necessary to quantify pressure flow waveforms in terms of hemodynamic energy levels to make a valid comparison between perfusion modes during chronic support The objective of this study was to quantify pressure flow waveforms in terms of energy equivalent pressure (EEP) and surplus hemodynamic energy (SHE) levels in an adult mock loop using a pulsatile ventricle assist system (VAD) A 70 cc Pierce-Donachy pneumatic pulsatile VAD was used with a Penn State adult mock loop The pump flow rate was kept constant at 5 L/min with pump rates of 70 and 80 bpm and mean aortic pressures (MAP) of 80, 90, and 100 mm Hg, respectively Pump flows were adjusted by varying the systolic pressure, systolic duration, and the diastolic vacuum of the pneumatic drive unit The aortic pressure was adjusted by varying the systemic resistance of the mock loop EEP (mm Hg) = (integral of fpdf)/(integral of fdt) SHE (ergs/cm3) = 1,332 [((integral of fpdt)/(integral of fdt))--MAP] were calculated at each experimental stage The difference between the EEP and the MAP is the extra energy generated by this device This difference is approximately 10% in a normal human heart The EEP levels were 883 +/- 09 mm Hg, 981 +/- 13 mm Hg, and 1074 +/- 10 mm Hg with a pump rate of 70 bpm and an aortic pressure of 80 mm Hg, 90 mm Hg, and 100 mm Hg, respectively Surplus hemodynamic energy in terms of ergs/cm3 was 11,039 +/- 1,236 ergs/cm3, 10,839 +/- 1,659 ergs/cm3, and 9,857 +/- 1,289 ergs/cm3, respectively The percentage change from the mean aortic pressure to EEP was 104 +/- 12%, 90 +/- 14%, and 74 +/- 10% at the same experimental stages Similar results were obtained when the pump rate was changed from 70 bpm to 80 bpm The EEP and SHE formulas are adequate to quantify different levels of pulsatility for direct and meaningful comparisons This particular pulsatile VAD system produces near physiologic hemodynamic energy levels at each experimental stage

Periodic acceleration: effects on vasoactive, fibrinolytic, and coagulation factors

Abstract: Cellular and isolated vessel experiments have shown that pulsatile and laminar shear stress to the endothelium produces significant release of mediators into the circulation. Periodic acceleration (pG(z)) applied to the whole body in the direction of the spinal axis adds pulses to the circulation, thereby increasing pulsatile and shear stress to the endothelium that should also cause release of mediators into the circulation. The purpose of this study was to determine whether addition of pulses to the circulation through pG(z) would be sufficient to increase shear stress in whole animals and to acutely release mediators and how such a physical maneuver might affect coagulation factors. Randomized control experiments were performed on anesthetized, supine piglets. The treatment group (pG(z)) (n = 12) received pG(z) with a motion platform that moved them repetitively head to foot at +/-0.4 g at 180 cpm for 60 min. The control group (n = 6) was secured to the platform but remained on conventional ventilation throughout the 4-h protocol. Compared with control animals and baseline, pulsatile stress produced significant increases of serum nitrite, prostacyclin, PGE(2), and tissue plasminogen activator antigen and activity, as well as D-dimer. There were no significant changes in epinephrine, norepinephrine, cortisol, and coagulation factors between groups or from baseline values. Pulsatile and laminar shear stress to the endothelium induced by pG(z) safely produces increases of vasoactive and fibrinolytic activity. pG(z) has potential to achieve mediator-related benefits from the actions of nitric oxide and prostaglandins.

Hemodynamic modes of ventricular assist with a rotary blood pump: continuous, pulsatile, and failure.

Abstract: Pulsatile operation of rotary blood pumps (RBPs) has received interest due to potential concern with nonphysiological hemodynamics. This study aimed to gain insight to the effects of various RBP modes on the heart-device interaction. A Deltastream diagonal pump (Medos Medizintechnik GmbH) was inserted in a cardiovascular simulator with apical-to-ascending aorta cannulation. The pump was run in continuous mode with incrementally increasing rotating speed (0-5000 rpm). This was repeated for three heart rates (50-100-150 bpm) and three levels of left ventricular (LV) contractility. Subsequently, the Deltastream was run in pulsatile mode to elucidate the effect of (de)synchronization between heart and pump. LV volume and pressure, arterial pressure, flows, and energetic parameters were used to evaluate the interaction. Pump failure (0 rpm) resulted in aortic pressure drops (17-46 mm Hg) from baseline. In continuous mode, pump flow compensated by diminished aortic flow, thus yielding constant total flow. High continuous rotating speed resulted in acute hypertension (mean aortic pressure up to 178 mm Hg). In pulsatile mode, unmatched heart and pulsatile pump rates yielded unphysiologic pressure and flow patterns and LV unloading was found to be highly dependent on synchronization phase. Optimal unloading was achieved when the minimum rotating speed occurred at end-systole. We conclude that, in continuous mode, a perfusion benefit can only be achieved if the continuous pump flow exceeds the preimplant (baseline) cardiac output. Pulsatile mode of support results in complex pressure and volume variations and requires accurate triggering to achieve optimal unloading.

Pulsatile flow increases the expression of eNOS, ET-1, and prostacyclin in a novel in vitro coculture model of the retinal vasculature.

Abstract: PURPOSE. By the development of a novel retinal microvascular endothelial and pericyte cell coculture system, this study determined the effects of pulsatile flow on the activation of the endothelial cell markers nitric oxide (NO), prostacyclin (PGI 2 ), and endothelin (ET)-1. METHODS. Monocultured bovine retinal endothelial cells (BRECs) and cocultured BRECs with bovine retinal pericytes (BRPs) were exposed to low flow (flow rate, 0.3 mL/min; pulse pressure, 6 mm Hg; shear stress, 0.5 dyne/cm 2 ) or high flow (flow rate, 25 mL/min; pulse pressure, 56 mm Hg; shear stress, 23 dynes/cm 2 ) for 24 hours, by using a novel perfused transcapillary culture system. The cells were characterized by immunohistochemistry and electron and confocal microscopy. Endothelial nitric oxide synthase (eNOS) and phosphorylated-eNos Ser1179 (pp-eNOS) were determined by Western blot analysis. Nitrate, PGI 2 , and ET-1 levels were quantified in the medium perfusate by using fluorometric and enzyme-linked immunosorbent assays, respectively. Activation of cyclooxygenase (COX)-2 in BRECs was determined by measuring COX-2 promoter activity with a luciferase reporter assay. RESULTS. The presence of BRPs and BRECs was confirmed by Western blot, immunocytochemistry, and scanning electron microscopy. Phosphorylated eNOS (pp-eNOS) protein levels in BRECs were significantly increased from low to high flow in both mono- and cocultures, concomitant with a significant increase in nitrate levels in the conditioned medium after exposure to pulsatile flow. In parallel cultures, PGI 2 levels were also significantly enhanced concomitant with an increase in the transactivation of a COX-2 promoter BREC after exposure to pulsatile flow. ET-1 levels were also increased in both mono- and cocultured cells. CONCLUSIONS. In this study a novel, functioning, in vitro model of retinal microvascular endothelial and pericyte cells that respond to changes in pulsatile flow was established.

Pulsatile tinnitus and the intrameatal vascular loop: why do we not hear our carotids?

Abstract: Objective: Pulsatile tinnitus is characterized by hearing the heart beat or respiration in one or both ears. In 15% of patients with pulsatile tinnitus, no cause can be found. Other investigators have suggested that a vascular loop entering the internal auditory meatus can be another cause of arterial, pulse synchronous tinnitus. If so, we should constantly hear the arterial pulsations of the carotid arteries passing through the petrous bone. Methods: Using magnetic resonance imaging, 17 patients with unilateral pulsatile tinnitus and 46 with non-pulsatile tinnitus were analyzed for the presence of a vascular loop entering into the internal acoustic meatus. Four temporal bones were sectioned to find structural differences between the internal acoustic meatus and the pericarotid area. Four patients with intrameatal vascular loops and ipsilateral pulsatile tinnitus underwent surgery by Teflon interpositioning between the loop and the cochlea. Results: In unilateral pulsatile tinnitus, a statistically highly significant amount of intrameatal vascular loops was noted in comparison to non-pulsatile tinnitus. A well-developed pericarotid venous plexus was found histologically. Three of the four patients who underwent surgery were initially tinnitus free, but pulsations recurred after 3 months in one patient. Conclusion: Vascular loops in the internal auditory canal may generate pulsatile tinnitus. It may be treated by placing Teflon between the cochlea and the intrameatal vascular loop. One then does not hear the pulsation of the carotids due to a dampening effect of a pericarotid venous plexus.

Suction detection for the MicroMed DeBakey Left Ventricular Assist Device.

Abstract: The MicroMed DeBakey Ventricular Assist Device (MicroMed Technology, Inc., Houston, TX) is a continuous axial flow pump designed for long-term circulatory support. The system received CE approval in 2001 as a bridge to transplantation and in 2004 as an alternative to transplantation. Low volume in the left ventricle or immoderate pump speed may cause ventricular collapse due to excessive suction. Suction causes decreased flow and may result in patient discomfort. Therefore, detection of this critical condition and immediate adaptive control of the device is desired. The purpose of this study is to evaluate and validate system parameters suitable for the reliable detection of suction. In vitro studies have been performed with a mock loop allowing pulsatile and nonpulsatile flow. Evidence of suction is clearly shown by the flow waveform reported by the implanted flow probe of the system. For redundancy to the implanted flow probe, it would be desirable to use the electronic motor signals of the pump for suction detection. The continuously accessible signals are motor current consumption and rotor/impeller speed. The influence of suction on these parameters has been investigated over a wide range of hydrodynamic conditions, and the significance of the respective signals individually or in combination has been explored. The reference signal for this analysis was the flow waveform of the ultrasonic probe. To achieve high reliability under both pulsatile and nonpulsatile conditions, it was determined that motor speed and current should be used concurrently for suction detection. Using the amplified differentiated current and speed signals, a suction-detection algorithm has been optimized, taking into account two different working points, defined by the value of the current input. The safety of this algorithm has been proven in vitro under pulsatile and nonpulsatile conditions over the full spectrum of possible speed and differential pressure variations. The algorithm described herein may be best utilized to provide redundancy to the existing flow based algorithm.