scispace - formally typeset
Search or ask a question

Showing papers on "Pulsatile flow published in 2002"


Journal ArticleDOI
TL;DR: A novel in vitro flow model was developed to simulate pulsatile shear stress waveforms encountered by the endothelium in the arterial circulation, revealing a unique responsiveness of ECs to an arterial waveform and begin to elucidate the complex sensing capabilities of the endot Helium to the dynamic characteristics of flows throughout the human vascular tree.
Abstract: In the circulation, flow-responsive endothelial cells (ECs) lining the lumen of blood vessels are continuously exposed to complex hemodynamic forces. To increase our understanding of EC response to these dynamic shearing forces, a novel in vitro flow model was developed to simulate pulsatile shear stress waveforms encountered by the endothelium in the arterial circulation. A modified waveform modeled after flow patterns in the human abdominal aorta was used to evaluate the biological responsiveness of human umbilical vein ECs to this new type of stimulus. Arterial pulsatile flow for 24 hours was compared to an equivalent time-average steady laminar shear stress, using no flow (static) culture conditions as a baseline. While both flow stimuli induced comparable changes in cell shape and alignment, distinct patterns of responses were observed in the distribution of actin stress fibers and vinculin-associated adhesion complexes, intrinsic migratory characteristics, and the expression of eNOS mRNA and protein. These results thus reveal a unique responsiveness of ECs to an arterial waveform and begin to elucidate the complex sensing capabilities of the endothelium to the dynamic characteristics of flows throughout the human vascular tree.

217 citations


Journal ArticleDOI
01 Feb 2002-Diabetes
TL;DR: The role of impaired pulsatile release in early type 2 diabetes suggests a predictive value of studies on insulin pulsatility in the development of this disease.
Abstract: Insulin concentrations oscillate at a periodicity of 5-15 min per oscillation. These oscillations are due to coordinate insulin secretory bursts, from millions of islets. The generation of common secretory bursts requires strong within-islet and within-pancreas coordination to synchronize the secretory activity from the beta-cell population. The overall contribution of this pulsatile mechanism dominates and accounts for the majority of insulin release. This review discusses the methods involved in the detection and quantification of periodicities and individual secretory bursts. The mechanism by which overall insulin secretion is regulated through changes in the pulsatile component is discussed for nerves, metabolites, hormones, and drugs. The impaired pulsatile secretion of insulin in type 2 diabetes has resulted in much focus on the impact of the insulin delivery pattern on insulin action, and improved action from oscillatory insulin exposure is demonstrated on liver, muscle, and adipose tissues. Therefore, not only is the dominant regulation of insulin through changes in secretory burst mass and amplitude, but the changes may affect insulin action. Finally, the role of impaired pulsatile release in early type 2 diabetes suggests a predictive value of studies on insulin pulsatility in the development of this disease.

209 citations


Journal ArticleDOI
TL;DR: The results of computational simulations may supplement MR and other in vivo diagnostic techniques to provide an accurate picture of the hemodynamics in particular vessels, which may help demonstrate the risks of embolism or plaque rupture posed by particular plaque deposits.
Abstract: The results of computational simulations may supplement MR and other in vivo diagnostic techniques to provide an accurate picture of the hemodynamics in particular vessels, which may help demonstrate the risks of embolism or plaque rupture posed by particular plaque deposits. In this study, a model based on an endarterectomy specimen of the plaque in a carotid bifurcation was examined. The flow conditions include steady flow at Reynolds numbers of 300, 600, and 900 as well as unsteady, pulsatile flow. Both dynamic pressure and wall shear stress are very high, with shear values up to 70 N/m 2 , proximal to the stenosis throat in the internal carotid artery, and both vary significantly through the flow cycle. The wall shear stress gradient is also strong along the throat. Vortex shedding is observed downstream of the most severe occlusion. Two turbulence models, the Chien and Goldberg varieties of k-«, are tested and evaluated for their relevance in this geometry. The Chien model better captures phenomena such as vortex shedding. The flow distal to stenosis is likely transitional, so a model that captures both laminar and turbulent behavior is needed. @DOI: @10.1115/1.1427042#

203 citations


Journal ArticleDOI
TL;DR: A model of intracranial pulsations based on the analogy between the pulsatile motion of electrons in an electrical circuit and the pulses of blood and CSF in the cranium is developed and it is proposed that communicating hydrocephalus is the result of a redistribution of CSF pulsations in thecranium.
Abstract: The traditional theory of communicating hydrocephalus has implicated the bulk flow component of CSF motion; that is, hydrocephalus is generally understood as an imbalance between CSF formation and absorption. The theory that the cause of communicating hydrocephalus is malabsorption of CSF at the arachnoid villi is not substantiated by experimental evidence or by physical reasoning. Flow-sensitive MRI has shown that nearly all CSF motion is pulsatile, and there is substantial evidence that hyperdynamic choroid plexus pulsations are necessary and sufficient for ventricular dilation in communicating hydrocephalus. We have developed a model of intracranial pulsations based on the analogy between the pulsatile motion of electrons in an electrical circuit and the pulsatile motion of blood and CSF in the cranium. Increased impedance to the flow of CSF pulsations in the subarachnoid space redistributes the flow of pulsations into the ventricular CSF and into the capillary and venous circulation. The salient features of communicating hydrocephalus, such as ventricular dilation, intracranial pressure waves, narrowing of the CSF-venous pressure gradient, diminished cerebral blood flow, elevated resistive index and malabsorption of CSF, emerge naturally from the model. We propose that communicating hydrocephalus is the result of a redistribution of CSF pulsations in the cranium.

190 citations


Journal ArticleDOI
TL;DR: In hypertensive patients pulse pressure, not mean pressure, is associated with an increased risk of fatal events, and this appears to be true in a broad range of patients with hypertension.
Abstract: ObjectiveAlthough current guidelines rest exclusively on the measurement of systolic and diastolic blood pressures, the arterial pressure wave is more precisely described as consisting of a pulsatile (pulse pressure) and a steady (mean pressure) component. This study explored the independent roles o

164 citations


Journal ArticleDOI
TL;DR: Data suggest that impaired pulsatile insulin secretion is an early marker for beta-cell dysfunction in Type II diabetes, and the role of early detection of impaired pulsatility to predict diabetes or to examine mechanisms to cause beta- cell dysfunction is mentioned.
Abstract: The presence of oscillations in peripheral insulin concentrations has sparked a number of studies evaluating the impact of the insulin release pattern on the action of insulin on target organs. These have convincingly shown that equal amounts of insulin presented to target organs have improved action when delivered in a pulsatile manner. In addition, impaired (not absent) pulsatility of insulin secretion has been demonstrated in Type II (non-insulin-dependent) diabetes mellitus, suggesting a possible mechanism to explain impaired insulin action in Type II diabetes. Whereas the regulation of overall insulin secretion has been described in detail, the mechanisms by which this regulation affects the pulsatile insulin secretory pattern, and the relative and absolute contribution of changes in the characteristics of pulsatile insulin release have not been reviewed previously. This review will focus on the importance of the secretory bursts to overall insulin release, and on how insulin secretion is adjusted by changes in these secretory bursts. Detection and quantification of secretory bursts depend on methods, and the methodology involved in studies dealing with pulsatile insulin secretion is described. Finally, data suggest that impaired pulsatile insulin secretion is an early marker for beta-cell dysfunction in Type II diabetes, and the role of early detection of impaired pulsatility to predict diabetes or to examine mechanisms to cause beta-cell dysfunction is mentioned.

162 citations


Journal ArticleDOI
TL;DR: A lattice Boltzmann method for simulating the viscous flow in large distensible blood vessels is presented by introducing a boundary condition for elastic and moving boundaries, and the numerical results for steady flow agree with the analytical prediction to very high accuracy.
Abstract: A lattice Boltzmann method for simulating the viscous flow in large distensible blood vessels is presented by introducing a boundary condition for elastic and moving boundaries. The mass conservation for the boundary condition is tested in detail. The viscous flow in elastic vessels is simulated with a pressure-radius relationship similar to that of the Pulmonary blood vessels. The numerical results for steady flow agree with the analytical prediction to very high accuracy, and the simulation results for pulsatile flow are comparable with those of the aortic flows observed experimentally. The model is expected to find many applications for studying blood flows in large distensible arteries, especially in those suffering from atherosclerosis. stenosis. aneurysm, etc.

150 citations


Journal ArticleDOI
TL;DR: This study resulted in a prototype of a compact pulsatile flow system for the creation of TE aortic valves, with controllable resistance, compliance, stroke volume and frequency, and hydrodynamic conditions can be changed over a wide physiological range.
Abstract: Evidence has been gathered that biomechanical factors have a significant impact on cell differentiation and behavior in in vitro cell cultures. The aim of this bioreactor is to create a physiological environment in which tissue engineered (TE) aortic valves seeded with human cells can be cultivated during a period of several days. The bioreactor consists of 2 major parts: the left ventricle (LV) and the afterload consisting of a compliance, representing the elastic function of the large arteries, and in series a resistance, mimicking the arterioles and capillaries. The TE aortic valve is placed between the LV and the compliance. With controllable resistance, compliance, stroke volume and frequency, and hydrodynamic conditions can be changed over a wide physiological range. This study resulted in a prototype of a compact pulsatile flow system for the creation of TE aortic valves. In addition a biocompatibility study of the used materials is performed.

121 citations


Journal ArticleDOI
TL;DR: A method to quantify wall shear stress in large blood vessels by differentiating velocity interpolation functions defined using cine phase-contrast MRI data on a band of elements in the neighborhood of the vessel wall is described.
Abstract: Arterial wall shear stress is hypothesized to be an important factor in the localization of atherosclerosis. Current methods to compute wall shear stress from magnetic resonance imaging (MRI) data do not account for flow profiles characteristic of pulsatile flow in noncircular vessel lumens. We describe a method to quantify wall shear stress in large blood vessels by differentiating velocity interpolation functions defined using cine phase-contrast MRI data on a band of elements in the neighborhood of the vessel wall. Validation was performed with software phantoms and an in vitro flow phantom. At an image resolution corresponding to in vivo imaging data of the human abdominal aorta, time-averaged, spatially averaged wall shear stress for steady and pulsatile flow were determined to be within 16% and 23% of the analytic solution, respectively. These errors were reduced to 5% and 8% with doubling in image resolution. For the pulsatile software phantom, the oscillation in shear stress was predicted to within 5%. The mean absolute error of circumferentially resolved shear stress for the nonaxisymmetric phantom decreased from 28% to 15% with a doubling in image resolution. The irregularly shaped phantom and in vitro investigation demonstrated convergence of the calculated values with increased image resolution. We quantified the shear stress at the supraceliac and infrarenal regions of a human abdominal aorta to be 3.4 and 2.3 dyn/cm2, respectively. © 2002 Biomedical Engineering Society.

120 citations


Journal ArticleDOI
TL;DR: It is considered that nonpulsatile devices can be used safely for long-term circulatory support and neither functional nor histologic changes in major end organs are found.

119 citations


Journal ArticleDOI
TL;DR: In the present computational analysis, pulsatile flow and vessel wall behaviour in a simplified model of a stenosed vessel were investigated, and qualitatively similar wall strain and stress patterns but considerable differences in magnitude were obtained.

Journal ArticleDOI
TL;DR: To investigate the effect of acquisition parameters on the accuracy of 2D velocity encoded cine magnetic resonance imaging (VEC MRI) flow measurements, a large number of VEC MRI machines are used for flow measurements.
Abstract: Purpose To investigate the effect of acquisition parameters on the accuracy of 2D velocity encoded cine magnetic resonance imaging (VEC MRI) flow measurements. Materials and Methods Using a pulsatile flow phantom, through-plane flow measurements were performed on a flexible vessel made of polyvinyl alcohol cryogel (PVA), a material that mimics the MR signal and biomechanical properties of aortic tissue. Results Repeated VEC MRI flow measurements (N = 20) under baseline conditions yielded an error of 0.8 ± 1.5%. Slice thickness, angle between flow and velocity encoding directions, spatial resolution, velocity encoding range, and radio frequency (RF) flip angles were varied over a clinically relevant range. Spatial resolution had the greatest impact on accuracy, with a 9% overestimation of flow at 16 pixels per vessel cross-section. Conclusion VEC MRI proved to be an accurate and reproducible technique for pulsatile flow measurements over the range of acquisition parameters examined as long as sufficient spatial resolution was prescribed. J. Magn. Reson. Imaging 2002;15:47–54. © 2002 Wiley-Liss, Inc.

Journal ArticleDOI
TL;DR: It was found that pulsatile flow significantly increased the rates at which EC elongated and realigned, compared to steady flow at ∂τ/∂t=0, and EC remodeling was faster in response to high than to low slew rates at a given tau τave.
Abstract: Shear stress modulates endothelial cell (EC) remodeling via realignment and elongation. We provide the first evidence that the upstroke slopes of pulsatile flow, defined as shear stress slew rates (positive ∂τ/∂τ affect significantly the rates at which ECs remodel. We designed a novel flow system to isolate various shear stress slew rates by precisely controlling the frequency, amplitude, and time-averaged shear stress τave of pulsatile flow. Bovine aortic endothelial cell (BAEC) monolayers were exposed to three conditions: (1) pulsatile flow (1 Hz) at high slew rate (293 dyn/cm2 s), (2) pulsatile flow (1 Hz) at low slew rate (71 dyn/cm2 s), and (3) steady laminar flow at ∂τ/∂t=0. All of the three conditions were operated at τave=50{dyn/cm}2. BAEC elongation and alignment were measured over 17 h. We were able to demonstrate the effects of shear stress slew rates ∂τ/∂t on EC remodeling at a fixed spatial shear stress gradient (∂τ/∂x). We found that pulsatile flow significantly increased the rates at which EC elongated and realigned, compared to steady flow at ∂τ/∂t=0. Furthermore, EC remodeling was faster in response to high than to low slew rates at a given tau τave © 2002 Biomedical Engineering Society. PAC2002: 8719Tt, 8719Rr

Journal ArticleDOI
TL;DR: These data provide the first direct account of how the pulmonary capillaries respond to pulsatile flow by showing that capillary are recruited during the systolic pulse and that, once open, the capillars remain open throughout the pulsatile cycle.
Abstract: Capillaries recruit when pulmonary arterial pressure rises. The duration of increased pressure imposed in such experiments is usually on the order of minutes, although recent work shows that the recruitment response can occur in <4 s. In the present study, we investigate whether the brief pressure rise during cardiac systole can also cause recruitment and whether the recruitment is maintained during diastole. To study these basic aspects of pulmonary capillary hemodynamics, isolated dog lungs were pump perfused alternately by steady flow and pulsatile flow with the mean arterial and left atrial pressures held constant. Several direct measurements of capillary recruitment were made with videomicroscopy. The total number and total length of perfused capillaries increased significantly during pulsatile flow by 94 and 105%, respectively. Of the newly recruited capillaries, 92% were perfused by red blood cells throughout the pulsatile cycle. These data provide the first direct account of how the pulmonary capillaries respond to pulsatile flow by showing that capillaries are recruited during the systolic pulse and that, once open, the capillaries remain open throughout the pulsatile cycle.

Journal ArticleDOI
TL;DR: Using this system, in vitro flow in bifurcations with both normal and stenosed lumen geometry can be studied, along with the effect of factors, such as stenosis geometry and flow rate, on the observed Doppler ultrasound (US) spectra and haemodynamic patterns.
Abstract: To investigate the correlation between disease severity and Doppler spectral measurements in the carotid artery bifurcation, a unique in vitro system has been developed that mimics the human vasculature with respect to both anatomy and flow perfusion. Agar-based carotid phantoms are perfused with a blood-mimicking fluid using a computer-controlled pump and realistic pulsatile flow waveform. A three-axis translational stage allows the lumen to be interrogated with a 0.6-μL Doppler sample volume at the desired spatial intervals using a semiautomated acquisition system, to collect 10 cardiac cycles of gated quadrature data at each site. Off-line analysis, including a 1024-point FFT, produces a 4-D ( i.e., time-varying 3-D) Doppler velocity data set with 1.3-cm/s velocity resolution and 12-ms temporal resolution. Using this system, in vitro flow in bifurcations with both normal and stenosed lumen geometry (from 30% to 80% stenosis by NASCET criteria) can be studied, along with the effect of factors, such as stenosis geometry (concentric vs. eccentric) and flow rate, on the observed Doppler ultrasound (US) spectra and haemodynamic patterns. (E-mail: dholdswo@irus.rri.ca)

Journal ArticleDOI
TL;DR: It is suggested that temporal gradients in fluid shear stress are potent stimuli of bone cell proliferation and inhibition of mitogen-activated protein (MAP)/ERK kinase (MEK1/2) reduced shear-induced ERK 1/2 phosphorylation and cell proliferation.
Abstract: Bone cells are subject to interstitial fluid flow (IFF) driven by venous pressure and mechanical loading. Rapid dynamic changes in mechanical loading cause transient gradients in IFF. The effects of pulsatile flow (temporal gradients in fluid shear) on rat UMR106 cells and rat primary osteoblastic cells were studied. Pulsatile flow induced a 95% increase in S-phase UMR106 cells compared with static controls. In contrast, ramped steady flow stimulated only a 3% increase. Similar patterns of S-phase induction were also observed in rat primary osteoblastic cells. Pulsatile flow significantly increased relative UMR106 cell number by 37 and 62% at 1.5 and 24 h, respectively. Pulsatile flow also significantly increased extracellular signal-regulated kinase (ERK1/2) phosphorylation by 418%, whereas ramped steady flow reduced ERK1/2 activation to 17% of control. Correspondingly, retinoblastoma protein was significantly phosphorylated by pulsatile fluid flow. Inhibition of mitogen-activated protein (MAP)/ERK kinase (MEK)1/2 by U0126 (a specific MEK1/2 inhibitor) reduced shear-induced ERK1/2 phosphorylation and cell proliferation. These findings suggest that temporal gradients in fluid shear stress are potent stimuli of bone cell proliferation.

Journal ArticleDOI
TL;DR: In this paper, the authors present a computational investigation of instabilities in pulsatile flow through a three-dimensional stenosis using a third-order high-resolution scheme and a non-linear multigrid algorithm.

Journal ArticleDOI
TL;DR: The temporal distribution of hemodynamic stresses in pulsatile flow and their physical implications in AAA rupture are discussed in Part II of this paper.
Abstract: Numerical predictions of blood flow patterns and hemodynamic stresses in Abdominal Aortic Aneurysms (AAAs) are performed in a two-aneurysm, axisymmetric, rigid wall model using the spectral element method. Homogeneous, Newtonian blood flow is simulated under steady conditions for the range of Reynolds numbers 10 < or =Re < or =2265. Flow hemodynamics are quantified by calculating the distributions of wall pressure (p(w)), wall shear stress (tau(w)), Wall Shear Stress Gradient (WSSG). A correlation between maximum values of hemodynamic stresses and Reynolds number is established, and the spatial distribution of WSSG is considered as a hemodynamic force that may cause damage to the arterial wall at an intermediate stage of AAA growth. The temporal distribution of hemodynamic stresses in pulsatile flow and their physical implications in AAA rupture are discussed in Part II of this paper.

Journal ArticleDOI
TL;DR: Pulsatile flow generates higher hemodynamic energy, enhancing cerebral and renal blood flow during and after CPB with DHCA in this model.
Abstract: Controversy over benefits of pulsatile flow after pediatric cardiopulmonary bypass (CPB) continues. Our study objectives were to first, quantify pressure and flow waveforms in terms of hemodynamic energy, using the energy equivalent (EEP) formula, for direct comparisons, and second, investigate effects of pulsatile versus nonpulsatile flow on cerebral and renal blood flow, and cerebral vascular resistance during and after CPB with deep hypothermic circulatory arrest (DHCA) in a neonatal piglet model. Fourteen piglets underwent perfusion with either an hydraulically driven dual-chamber physiologic pulsatile pump (P, n = 7) or a conventional nonpulsatile roller pump (NP, n = 7). The radiolabeled microsphere technique was used to determine the cerebral and renal blood flow. P produced higher hemodynamic energy (from mean arterial pressure to EEP) compared to NP during normothermic CPB (13 +/- 3% versus 1 +/- 1%, p < 0.0001), hypothermic CPB (15 +/- 4% versus 1 +/- 1%, p < 0.0001) and after rewarming (16 +/- 5% versus 1 +/- 1%, p < 0.0001). Global cerebral blood flow was higher for P compared to NP during CPB (104 +/- 12 ml/100g/min versus 70 +/- 8 ml/100g/min, p < 0.05). In the right and left hemispheres, cerebellum, basal ganglia, and brainstem, blood flow resembled the global cerebral blood flow. Cerebral vascular resistance was lower (p < 0.007) and renal blood flow was improved fourfold (p < 0.05) for P versus NP, after CPB. Pulsatile flow generates higher hemodynamic energy, enhancing cerebral and renal blood flow during and after CPB with DHCA in this model.

Journal ArticleDOI
TL;DR: This work has developed a novel method for the in vitro development of tubular vascular structures by using a mechanical ventilator to induce pulsatile, laminar flow into a fluid column, resulting in pressurized waveforms similar to mammalian physiology.
Abstract: Exposure of vascular cell-seeded, tubular, biodegradable polymers to pulsatile flow conditions has been proposed as a method to develop tissue-engineered blood vessels by "maturing" structural integrity, and increasing collagen content, suture retention, burst pressure, and tissue formation. These in vitro tissue-engineered arteries demonstrate contractile responses to pharmacologic agents and express markers of vascular differentiation. Current methods to induce pulsatile flow in a bioreactor system are limited by the creation of nonphysiologic pressure waveforms and noncompliant reservoirs to house the tissue-engineered vascular constructs. We have developed a novel method for the in vitro development of tubular vascular structures by using a mechanical ventilator to induce pulsatile, laminar flow into a fluid column, resulting in pressurized waveforms similar to mammalian physiology. The vascular constructs are housed in semicompliant tubing to facilitate an additional variable of circumferential stretch as a potential signaling mechanism. This approach more closely approximates mammalian physiology and we hypothesize that it will facilitate mechanical signaling necessary for the development of tissue-engineered vessels for clinical applications.

Journal ArticleDOI
TL;DR: Numerical simulations of pulsatile, non-Newtonian blood flow through life-like femorodistal bypass models have been performed to determine whether haemodynamic benefits arise from the modified geometry of the Taylor anastomosis.

Journal ArticleDOI
TL;DR: Arterial wall elasticity assessed through E(inc) was strongly influenced by blood viscosity, probably due to presence or absence of endothelium relaxing factors or to direct shear smooth muscle activation when endothelial cells are removed.
Abstract: The role of blood viscosity on arterial wall elasticity before and after deendothelization (DE) was studied. Seven ovine brachiocephalic arteries were studied in vitro under physiological pulsatile...

Journal ArticleDOI
TL;DR: In this article, the accuracy of the lattice Boltzmann BGK method in simulating pulsatile flow in a 2D channel and a 3D tube has been analyzed, and the influence of different boundary conditions such as the bounce-back and inlet-outlet boundary conditions on the accuracy was studied.
Abstract: We present detailed analysis of the accuracy of the lattice Boltzmann BGK method in simulating pulsatile flow in a 2D channel and a 3D tube. For the 2D oscillatory flow, we have observed a half time-steps shift between the theory and the simulation, that enhances the accuracy at least one order of magnitude. For 3D tube flow, we have tested the accuracy of the lattice Boltzmann BGK method in recovering the Womersley solution for pulsatile flow in a rigid tube with a sinusoidal pressure gradient. The obtained flow parameters have been compared to the analytical solutions. The influence of different boundary conditions such as the bounce-back and inlet-outlet boundary conditions on the accuracy was studied. Relative errors of the order of 0.001 in 2D with the bounce back on the nodes have been achieved. For the 3D simulations, it has been possible to reduce the error from 15% with the simple bounce-back to less than 5% with a curved boundary condition.

Journal ArticleDOI
TL;DR: Pulsatile flow generates significantly higher energy, enhancing myocardial flow during and after hypothermic CPB and after 60 minutes of ischemia in this model.
Abstract: Pediatric myocardial related morbidity and mortality after cardiopulmonary bypass (CPB) are well documented, but the effects of pulsatile perfusion (PP) versus nonpulsatile perfusion (NPP) on myocardial blood flow during and after hypothermic CPB are unclear. After investigating the effects of PP versus NPP on myocardial flow during and after hypothermic CPB, we quantified PP and NPP pressure and flow waveforms in terms of the energy equivalent pressure (EEP) for direct comparison. Ten piglets underwent PP (n = 5) or NPP (n = 5). After initiation of CPB, all animals underwent 15 minutes of core cooling (25 degrees C), 60 minutes of hypothermic CPB with aortic cross-clamping, 10 minutes of cold reperfusion, and 30 minutes of rewarming. During CPB, the mean arterial pressure (MAP) and pump flow rates were 40 mm Hg and 150 ml/kg per min, respectively. Regional flows were measured with radiolabeled microspheres. During normothermic CPB, left ventricular flow was higher in the PP than the NPP group (202+/-25 vs. 122+/-20 ml/l 00 g per min). During hypothermic CPB, no significant intragroup differences were observed. After 60 minutes of ischemia and after rewarming (276+/-48 vs. 140+/-12 ml/100 g per min; p < 0.05) and after CPB (271+/-10 vs. 130+/-14 ml/100 g per min; p < 0.05), left ventricular flow was higher in the PP group. Right ventricular flow resembled left ventricular flow. The pressure increase (from MAP to EEP) was 10+/-2% with PP and 1% with NPP (p < 0.0001). The increase in extracorporeal circuit pressure (ECCP) (from ECCP to EEP) was 33+/-10% with PP and 3% with NPP (p < 0.0001). Pulsatile flow generates significantly higher energy, enhancing myocardial flow during and after hypothermic CPB and after 60 minutes of ischemia in this model.

Journal ArticleDOI
TL;DR: The findings of this study suggest that selective use of high-pressure irrigation in the management of open fractures appears warranted, and alternative strategies that optimize bacterial removal from soft tissues while preserving bone architecture will need to be investigated.
Abstract: OBJECTIVES To evaluate the effect of both high-pressure pulsatile lavage and bulb syringe irrigation on the biomechanical parameters of fracture healing using an in vivo open noncontaminated diaphyseal femoral fracture model in rats. BACKGROUND The utility of high-pressure pulsatile lavage irrigation on soft tissue debridement has been extrapolated to a similar perceived benefit in the debridement of bone. However, there have been several reports of a possible deleterious effect that high-pressure pulsatile lavage may have on bone architecture, intramedullary bacterial and contaminant seeding, and fracture healing. Although a previous in vivo histologic study suggests damage to bone architecture and impairment of early bone formation, it remains unclear whether these microscopic findings translate to a detectable decline in the biomechanical strength of the healing fracture. To our knowledge, there have been no reports of the in vivo effects high-pressure pulsatile lavage on fracture healing in open diaphyseal fractures. MATERIALS AND METHODS Using sterile technique, standard open transverse mid-shaft femur fractures were created in thirty-six rats randomized into three groups: a control group underwent retrograde intramedullary pinning only; a bulb syringe irrigation group and a high-pressure pulsatile lavage group underwent identical procedures as the control group, except that the osteotomy site was irrigated with bulb syringe irrigation and high-pressure pulsatile lavage, respectively, before insertion of the intramedullary pin. Six rats from each group were killed at three weeks and six weeks, and the femora was mechanically tested in bending. RESULTS Mechanical testing of the thirty-six femora revealed that the peak bending force (17.7 +/- 10.2 N) and stiffness (21.2 +/- 5.1 N/mm) of the healing fracture in the high-pressure irrigation group were significantly lower at three weeks when compared with the control (peak force, 28.1 +/- 5.9 N; stiffness, 31.4 +/- 5.8 N/mm) and the bulb syringe (peak force, 27.7 +/- 3.3 N; stiffness, 23.6 +/- 4.5 N/mm) irrigation groups (p < 0.05). The 37 percent lower peak bending force and 32 percent lower stiffness in the high-pressure pulsatile lavage group after three weeks of fracture healing were not present in the femora tested at six weeks. The high-pressure pulsatile lavage group did reveal a trend toward a lower peak bending force and stiffness after six weeks of fracture healing when compared with the control and bulb syringe irrigation groups, but the differences were not statistically significant at the 95 percent level. CONCLUSIONS The use of high-pressure pulsatile lavage in open noncontaminated diaphyseal femur fractures in rats has a significant negative impact on the mechanical strength of the fracture callous during the early phases (three weeks) of fracture healing. However, it appears that the early deleterious effect of high-pressure pulsatile irrigation is not apparent in the late phases (six weeks) of fracture healing. Further study is required to evaluate the effect of high-pressure pulsatile lavage on fracture healing in the presence of wound contamination, fracture comminution, and soft tissue damage. CLINICAL SIGNIFICANCE The findings of this study suggest that selective use of high-pressure irrigation in the management of open fractures appears warranted. In situations in which high-pressure lavage may be deleterious to bone healing, alternative strategies that optimize bacterial removal from soft tissues while preserving bone architecture will need to be investigated.

Journal ArticleDOI
TL;DR: These results suggest that pulsatile flow stimulates angiogenesis and that this effect is mediated by activation of Gi&agr;1 or Gi-3, but not G&bgr;&ggr;, subunits.
Abstract: Objective— Angiogenesis plays a key role in the growth and function of normal and pathological tissues. We investigated the effect of pulsatile flow on endothelial cell (EC) in vitro angiogenic activity. Methods and Results— Bovine aortic ECs were exposed to “static” or “flow” (1.2 to 67.0 mL/min, shear stress 1.4 to 19.2 dyne/cm2) conditions for 2 to 24 hours. After exposure, angiogenesis was measured as tubule formation on Matrigel, and EC migration was assessed by filter migration assay. Pulsatile flow increased angiogenesis and EC migration in a temporal and force-dependent manner, with a maximal effect at 16 hours (13.2 dyne/cm2). Pertussis toxin completely inhibited the effect of pulsatile flow on angiogenesis and migration. Transfection of ECs with inhibitory mutants of the α subunit of Gi1 or Gi3, but not Gi2, inhibited the flow-induced angiogenic response by 61±2% and 32±6%, respectively, whereas transfection with constitutively activated mutants of the α subunit of Gi1 or Gi3, but not Gi2, increased the flow-induced response by 202±23% and 70±4%, respectively. In contrast, inhibition of Gβγ by the carboxy terminal fragment of β-adrenergic receptor kinase overexpression increased the flow-induced response by 82±8%. Conclusions— These results suggest that pulsatile flow stimulates angiogenesis and that this effect is mediated by activation of Giα1 or Giα3, but not Gβγ, subunits.

Journal ArticleDOI
TL;DR: The results indicate that 1 week after latanoprost application, POBF, OPA and OPV were significantly increased in the eyes treated, and more information on the perfusion of the optic nerve head is needed before the relevance of these findings to optic nerveHead blood flow can be interpreted correctly.
Abstract: . Purpose: There is evidence that ocular blood flow plays a critical role in the clinical course of glaucoma. Any reduction in ocular blood flow due to topical antiglaucoma treatment should therefore be avoided. This study aimed to evaluate the short-term effect of local latanoprost application on ocular hemodynamics. Methods: Intraocular pressure (IOP), ocular pulse amplitude (OPA), ocular pulse volume (OPV), systemic blood pressure, heart rate and the pulsatile component of ocular blood flow (POBF) were recorded using a pneumotonometer linked to the Langham Ocular Blood Flow System in 24 patients in a prospective, open-label study before and after 1 week of topical latanoprost application in both eyes. Twenty of the subjects had primary open-angle glaucoma and four had ocular hypertension. Results: After 1 week of latanoprost treatment, IOP decreased significantly 6.2 ± 2.9 mmHg in OD (P < 0.001) and 6.2 ± 3.2 mmHg in OS (P < 0.001). Pulsatile OBF increased significantly by 201.2 ± 167.4 µL/min in OD (P < 0.001) and 203.8 ± 187.3 µL/min in OS (P < 0.001). Ocular pulse amplitude and OPV showed statistically significant increases (P < 0.05 and P < 0.001 respectively). Blood pressure and heart rate did not change significantly. Conclusion: Our results indicate that 1 week after latanoprost application, POBF, OPA and OPV were significantly increased in the eyes treated. More information on the perfusion of the optic nerve head is needed before the relevance of these findings to optic nerve head blood flow can be interpreted correctly.

Journal ArticleDOI
TL;DR: Real‐time three‐dimensional echocardiography can accurately quantify right ventricle cavity volumes and stroke volumes without geometric assumptions.
Abstract: OBJECTIVE The complex structural geometry of the right ventricle hinders accurate assessment of right ventricular volume and function on conventional two-dimensional echocardiography. We sought to evaluate the accuracy of real-time three-dimensional echocardiography for quantifying the volume of the right ventricle in an in vitro experimental study. METHODS We developed 39 anatomically accurate latex phantoms of human and porcine right ventricles (range, 24-108 mL) for 39 static and 10 pulsatile models. Real-time three-dimensional scanning was performed with the models placed in a water bath and with a 3.5-MHz probe. In the dynamic models a pulsatile flow pump generated 2 different stroke volumes (29 and 64 mL/beat). Static chamber volumes and stroke volumes were verified by water displacement, which served as a reference standard. Three-dimensional echo right ventricle volumes were determined by tracing derived B- and C-scans, using the Simpson rule. RESULTS Multiple regression analyses showed an excellent correlation between real-time three-dimensional echocardiographic determinations and the static volumes (B-scan, r = 0.99; C-scan, r = 0.98; P < .001), as well as stroke volumes in the dynamic model (B-scan, r = 0.90; C-scan, r = 0.86; P < .001). However, the C-scans tended to underestimate cavity and stroke volumes more than the B-scans (mean difference for static volume: B-scan, 1.4% +/- 9.8%; C-scan, -7.4% +/- 8.0%; P < .001; mean difference for stroke volumes: B-scan, 3.0% +/- 19.1%; C-scan, -2.5% +/- 20.9%; P < .001). CONCLUSIONS Real-time three-dimensional echocardiography can accurately quantify right ventricle cavity volumes and stroke volumes without geometric assumptions.

Journal ArticleDOI
TL;DR: The suppressive action of orexin A on pulsatile LH secretion is potentiated by estrogen, suggesting a modulation by estrogen of the response to orexins.
Abstract: Orexins are hypothalamic neuropeptides which stimulate luteinizing hormone (LH) secretion in estrogen- and progesterone-treated ovariectomized (OVX) rats and suppress it in OVX rats not treated with estrogen, suggesting a modulation by estrogen of the response to orexins. We examined the effects of orexin A on pulsatile LH secretion in OVX rats treated with a very small dose of estrogen so as to maintain the pulsatile secretion of LH. The estrogen treatment was done 24 h before the blood sampling by subcutaneously implanting a silicone tube (id = 1.5 mm, od = 2.5 mm, length = 25 mm) containing 17beta-estradiol (E(2)) dissolved in sesame oil at 20 microg/ml. In OVX rats treated with sesame oil as a control, the intracerebroventricular (icv) injection of orexin A (0.3 nmol, dissolved in 3 microl artificial cerebrospinal fluid) had no significant effect on the parameters of pulsatile LH secretion, i.e., pulse frequency and pulse amplitude, although it caused a small but statistically significant decrease in overall mean LH concentrations within 1 h. In OVX rats treated with E(2), the icv injection of orexin A significantly suppressed the pulsatile LH secretion; the frequency decreased for more than 2 h, inducing a rapid decline in overall mean LH concentrations. In view of the finding that a much higher dose of orexin A suppresses pulsatile LH secretion in OVX rats not treated with E(2), we suggest that the suppressive action of orexin A on pulsatile LH secretion is potentiated by estrogen.

Journal ArticleDOI
TL;DR: A deconvolution technique previously developed for measurement of pulsatile hormone secretion in vivo was specifically validated for in vitro pulse detection and recovered quantitatively the insulin secretion profile, insulin secretion rate, and insulin pulse mass from single as well as multiple perifused islets.
Abstract: Insulin is secreted in discrete bursts. These pulses are also present when individual or groups of islets are perifused. Interpretation of the measured frequency and magnitude of pulsatile hormone secretion requires an examination of the sensitivity and specificity of the methods for pulse detection and validation of these for the experimental apparatus and hormone assay in which they are applied. In the present study we achieve these aims for a perfusion method for measurement of pulsatile insulin release by human islets. A deconvolution technique previously developed for measurement of pulsatile hormone secretion in vivo was specifically validated for in vitro pulse detection in the present study. Deconvolution analysis reliably (>90%) detected insulin pulses with an amplitude 20% or more above baseline and recovered quantitatively the insulin secretion profile, insulin secretion rate, and insulin pulse mass from single as well as multiple perifused islets. Cluster analysis was less sensitive, but was able to detect most (>80%) pulses with an amplitude of 40% or more above baseline. With this limitation, cluster analysis is potentially useful for groups, but not single perifused human islets. Analysis of single human islets showed that enhanced insulin secretion by increased glucose concentrations in the perfusate is achieved by enhancing insulin pulse mass with no change in pulse frequency. Perfused single or groups of human islets exhibited an interpulse interval (6 – 8 min) comparable to that observed in humans in vivo. Dynamic in vitro perifusion should facilitate studies of the mechanisms driving pulsatile insulin secretion. (J Clin Endocrinol Metab 87: 213–221, 2002)