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Physiological flow simulation in residual human stenoses after coronary angioplasty.

To evaluate the local hemodynamic implications of coronary artery balloon angioplasty, computational fluid dynamics (CFD) was applied in a group of patients previously reported by [Wilson et al. (1988), 77, pp. 873-885] with representative stenosis geometry post-angioplasty and with measured values of coronary flow reserve returning to a normal range (3.6 +/- 0.3). During undisturbed flow in the absence of diagnostic catheter sensors within the lesions, the computed mean pressure drop delta p was only about 1 mmHg at basal flow, and increased moderately to about 8 mmHg for hyperemic flow. Corresponding elevated levels of mean wall shear stress in the midthroat region of the residual stenoses, which are common after angioplasty procedures, increased from about 60 to 290 dynes/cm2 during hyperemia. The computations (Ree approximately equal to 100-400; alpha e = 2.25) indicated that the pulsatile flow field was principally quasi-steady during the cardiac cycle, but there was phase lag in the pressure drop-mean velocity (delta p - u) relation. Time-averaged pressure drop values, delta p, were about 20 percent higher than calculated pressure drop values, delta ps, for steady flow, similar to previous in vitro measurements by Cho et al. (1983). In the throat region, viscous effects were confined to the near-wall region, and entrance effects were evident during the cardiac cycle. Proximal to the lesion, velocity profiles deviated from parabolic shape at lower velocities during the cardiac cycle. The flow field was very complex in the oscillatory separated flow reattachment region in the distal vessel where pressure recovery occurred. These results may also serve as a useful reference against catheter-measured pressure drops and velocity ratios (hemodynamic endpoints) and arteriographic (anatomic) endpoints post-angioplasty. Some comparisons to previous studies of flow through stenoses models are also shown for perspective purposes.

Angioplasty, Balloon, Coronary↗

Laser Doppler anemometry measurements of the shear stresses on ultrasonic contrast agent microbubbles attached to agar.

Ultrasonic contrast agents are currently being developed to target and bind to specific areas of interest such as atheromous plaque. A microbubble has been developed in-house which can be targeted to attach to specific cell-lines. To assess the feasibility of using the microbubble in vivo, the shear stresses which the bound microbubbles can withstand need to be known. A flow chamber was developed for use with intravascular ultrasound (IVUS) and laser Doppler anemometry (LDA). Biotin was incorporated into the microbubble shells and streptavidin was used to attach them to agar. IVUS at 40 MHz was then used to image the attached microbubbles under steady flow at a range of flow rates from 75 to 480 mL min(-1) through a flow area of 9 mm(2). LDA was employed to find high resolution velocity profiles of the flow in the chamber at a selection of these flow rates and the shear stresses on the bubbles were calculated. The bubbles were found to remain attached to the agar for shear stresses of up to 3.4 Pa. This compares with mean physiological arterial shear stresses of less than 1.5 Pa for pulsatile flow.

Agar↗

Thrombolysis, flow, and vessel wall interactions.

Vascular endothelium remains a dynamic interface between blood, blood platelets, and the vessel wall. New developments make clear that many antithrombotic and prothrombotic responses of the endothelium depend on flow conditions in an adaptive manner: duration of a certain level of shear stress matters as well as level of shear. In general, over the course of several hours, endothelium appears to be more actively antithrombotic under moderate shear conditions (eg, 15 dyne/cm2) and more fibrinolytic under high shear conditions (eg, 30 dyne/cm2). Pulsatile flow and cyclic wall stress further modify these responses. Special consideration, moreover, must be given to branch points and regions of irregular geometry (ie, stenoses, aneurysms) in the circulation. In such locations-predilection sites for thrombosis, lipid uptake, and atherosclerosis-low levels of shear stress (eg, 0.5 dyne/cm2), large gradients in shear stress, and vessel wall bending stresses all become important. Preliminary work suggests that endothelial cells in such regions can become prothrombotic, leading to localized platelet adhesion/aggregation and fibrin formation on subendothelium and perhaps deeper structures following vessel injury. Flow effects on thrombolysis remain largely unstudied.

Animals↗

Analysis of regurgitation, mean systolic pressure drop and energy losses for two artificial aortic valves.

The work reported here is related to the hydrodynamic performance of a Jellyfish valve and St Vincent valve in terms of total energy losses, mean systolic pressure drop and regurgitation. The in vitro experimental investigation was conducted at cardiac outputs of 3.5, 4.5 and 6.51 min-1 across the two valves and under pulsatile flow condition. It was found that the closure volume of the St Vincent valve was about 2.5 times higher than that of the Jellyfish valve. The total back flow losses on the other hand were found to be in the range of 36.5 to 107.1 and 85.5 to 192.5 mJ for the Jellyfish valve and St Vincent valve respectively. Moreover, the mean systolic pressure drop of the St Vincent valve was found to be higher than that of the Jellyfish valve. However, for all the operating conditions tested here, the Jellyfish valve showed superior hydrodynamic performance in terms of backflow and mean systolic pressure as well as energy losses.

Aortic Valve↗

First trimester umbilical venous Doppler sonography in chromosomally normal and abnormal fetuses.

In 342 singleton pregnancies in which the patients were undergoing chorionic villus sampling at 11 to 14 weeks of gestation, color Doppler sonography was used to obtain waveforms from the umbilical cord. The prevalence of pulsatile flow in the umbilical vein was higher in the 18 fetuses with trisomy 18 or 13 (16 of 18; 88.9%) than in the 18 fetuses with trisomy 21 (6 of 18; 33.3%) or the 302 chromosomally normal fetuses (73 of 302; 24.2%).

Aneuploidy↗

Flow-weighted MRI of the lungs with the ECG-gated half-Fourier FSE technique: evaluation of the effect of the cardiac cycle.

We investigated temporal MR signal changes in the peripheral lung and proximal pulmonary vessels during the entire cardiac cycle in order to evaluate the characteristics of the diastolic-systolic subtraction method in the lung. In eight healthy volunteers free of lung diseases, changes in the MR signal during one breath-hold were investigated with the multiple ECG-triggered half-Fourier single-shot fast-spin echo (SS-FSE) technique. The signal intensity-time course curve in the lung showed that biphasic signals decreased 20% to 47% at systole and 5% to 33% at mid-diastole, measured against the maximum signals at late diastole. This signal decrease in the peripheral lung was correlated to that in the proximal pulmonary vessels during an entire cardiac cycle (r=0.667 to 1.000). The best visualization of the lung was obtained at late diastole, when the intra-vascular flow in the lung was expected to be stagnant. Compared with the late diastolic SS-FSE images, the late diastolic-systolic subtracted SS-FSE images improved the signal-to-noise ratio in the lung as well as the signal-intensity ratio of the peripheral lung to surrounding tissues. Although the flow-induced signal dephasing in the lung was completely unavoidable and its amount was unpredictable even at late diastole, the diastolic-systolic subtracted SS-FSE images showed the relative differences in flow alteration during the cardiac cycle between the images at diastole and those at systole. The main characteristic of diastolic-systolic subtracted SS-FSE was the enhancement of visibility of cardiac-dependent signal changes in the lung due to the alteration in pulsatile flow.

Adult↗

Directional velocity estimation using focusing along the flow direction. I: Theory and simulation.

A new method for directional velocity estimation is presented. The method uses beamformation along the flow direction to generate data in which the correct velocity magnitude can be directly estimated from the shift in position of the received consecutive signals. The shift is found by cross-correlating the beamformed lines. The approach can find the velocity in any direction, including transverse to the traditionally emitted ultrasound beam. The velocity estimation is studied through extensive simulations using Field II. A 128-element, 7-MHz linear array is used. A parabolic velocity profile with a peak velocity of 0.5 m/s is simulated for different beam-to-flow angles and for different emit foci. At 45 degrees the relative standard deviation over the profile is 1.6% for a transmit focus at 40 mm. At 90 degrees the approach gave a relative standard deviation of 6.6% with a transmit focus of 80 mm, when using 8 pulse-echo lines and stationary echo canceling. Pulsatile flow in the femoral artery was also simulated using Womersley's flow model. A purely transverse flow profile could be obtained with a relative standard deviation of less than 10% over the whole cardiac cycle using 8 pulse emissions for each imaging direction, which is sufficient to show clinically relevant transverse color flow images.

Blood Flow Velocity↗

Effect of pressure-flow relationship of centrifugal pump on in vivo hemodynamics: a consideration for design.

We have been developing centrifugal pumps for an implantable left ventricular assist device. We manufactured 2 prototype centrifugal pumps (PI, PII). These two have similar designs except for the PII having a volute casing and a large output port. To determine the differences in the hydraulic characteristics between the PI and PII, we carried out in vitro and in vivo experiments. In vitro study showed that the PII had a shallower H-Q curve than that of the PI, and the PII required a pump speed faster than the PI for the same flow rate and pressure head. On the other hand, in vivo study showed that the PII demonstrated a flow pulsatility greater than that of the PI at 1,900 rpm and 8 L/min although no significant change was observed at low pump speeds (< or = 1,500 rpm). This greater pulsatility consisted of a large discharge according to the small differential pressure during the systolic phase and a small discharge according to the large differential pressure during the diastolic phase. In contrast, the PI, having the steeper H-Q curve, showed a small discharge in the systolic phase and a large discharge in the diastolic phase. These results showed that pulsatility synchronized with the native heart beating depended on the slope of the H-Q curve. As a result, the slope of the H-Q curve is important to determine the component of pulsatility synchronized with native cardiac output. Regarding the slope of the H-Q curve, a pump having a volute casing and a large outlet port demonstrates a shallow slope in the H-Q curve. In conclusion, we suggest that a centrifugal pump for use in left ventricular aortic bypass should be designed considering the effect on the native heart pulsatility.

Animals↗

DIDECMO: a new polymethylpentene oxygenator for pediatric extracorporeal membrane oxygenation.

We reviewed the performance of a new polymethylpentene oxygenator (DIDECMO, Dideco, Mirandola, Italy) in terms of clinical safety and efficiency in priming, oxygenation, and oxygenator resistance in neonatal and pediatric extracorporeal membrane oxygenation (ECMO) patients. Between March 2005 and January 2006, 14 patients required ECMO in the San Vincenzo Hospital. Of these, 8 (median age, 9 days; range, 3 days to 15 months) received normothermic ECMO for postcardiotomy heart failure after surgery for congenital heart disease. The DIDECMO oxygenator was used in all patients (median weight, 2.4 kg; range, 2 to 7 kg). According to our previous experience, all patients received the same anticoagulation management. DIDECMO is a new phosphorylcholine-coated, polymethylpentene hollow-fiber oxygenator recommended for a maximum blood flow of 2300 ml/min with a membrane surface area of 0.67 m2 and validated to be used up to 5 days. Static priming was 100 ml and mean support time 05 hours (range, 36 to 198 hours). No oxygenators were changed during support. Median pressure drop during overall assistance was 24 mm Hg. Carbon dioxide elimination was obtained with a 1:1 blood flow/air flow ratio. Neither oxygenator-related major nor minor adverse events occurred during support. In our initial experience, the new polymethylpentene DIDECMO oxygenator provided adequate gas exchange and offered technical advantages in terms of low priming volume and acceptable hemodynamic resistance despite pulsatile flow regimen. Also, we used this device for more than 8 days without any technical problems.

Cardiac Output, Low↗

Cardiac output during cardiopulmonary bypass. Animal experiments as a guide to flow rate.

Superior total body perfusion during cardiopulmonary bypass in dogs is achieved by duplicating, in each individual case, the actual operative cardiac output, rather than by relying on the currently recommended perfusion flow rates.A highly accurate method of measuring the cardiac output is presented using the gated sinewave electromagnetic flowmeter. Simplicity and sensitivity of the method enable the operator to measure the flow in situ (in the intact canine ascending aorta) and thus to determine a truly representative cardiac output before the cardiopulmonary bypass is effected. An adjustable hydraulic pump in conjunction with the electromagnetic flowmeter is used to substitute the natural cardiac action in order to maintain the normal hemodynamic state by providing a pulsatile flow of proper magnitude. The procedure is technically simple and, supported by favorable experimental evidence, is recommended for clinical use in open heart operations.

Animal Experimentation↗

Comparison of pulsatile ocular blood flow in Indians and Europeans.

PURPOSE: To compare pulsatile ocular blood flow (POBF) in Europeans and Indians and provide reference values for a group of healthy Indians. PATIENTS AND METHODS: Measurement with the POBF Tonograph was performed on healthy Indian subjects in India (n=252). A further 80 subjects (40 of Indian descent and 40 Europeans) underwent measurements in Cambridge, England. The instrument used for measurement was the same for both the studies. RESULTS: The mean POBF in the Indians in India was found to be 1176 microl/min. The mean POBF value in the Europeans was found to be 1033 microl/min and that for Indians in England was 1061 microl/min. The difference between the POBF within groups was significant (one-way ANOVA P<0.05) with the POBF of Indians in India being higher than Europeans and Indians in the UK. The difference between the Europeans and Indians in the UK did not reach statistical significance. CONCLUSIONS: POBF values in Indians living in India were found to be considerably higher than the previously published normal value of 650 microl/min in European studies and other studies for other racial groups. The reason for this apparent difference may be instrument-related rather than genetic because such a large difference was not observed when a comparison was performed in the UK. In addition, the results for both groups in our comparative study were still considerably higher than reported in previous studies. The POBF of Indians in India is slightly higher than the POBF of people of Indian ethnic origin in England.

Adolescent↗

MR phase-contrast flow measurement with limited spatial resolution in small vessels: value of model-based image analysis.

Magnetic resonance phase-contrast volume flow rate (VFR) measurement with limited resolution in small vessels is subject to two major sources of error: a) partial volume artifacts, causing systematic overestimation of the VFR, and b) errors related to the selection of vessel pixels [region of interest (ROI)], causing large inter-observer and intra-observer variability. Additionally, limited resolution results in Gibbs-ringing around vessels, which adversely affects VFR determination. In this paper, a semi-automatic model-based method is presented that effectively eliminates errors due to both partial volume effect and Gibbs-ringing and also minimizes errors from variability in the ROI selection. The model assumes a parabolic flow profile and cylindrical vessel geometry, incorporates inflow effects, and takes into account the point-spread function of the acquisition. The method automatically estimates maximum velocity, vessel radius, and VFR. The method is validated in phantoms under various conditions and evaluated in vivo. For small vessels with moderately pulsatile flow, it is demonstrated that accurate VFRs and diameter estimates are obtained, virtually independent of the ROI selection, even in vessels covered by just a few pixels. Compared with conventional VFR analysis, both accuracy and reproducibility improve significantly.

Basilar Artery↗

The hemodynamic effects of mechanical prosthetic valve type and orientation on fluid mechanical energy loss and pressure drop in in vitro models of ventricular hypertrophy.

BACKGROUND AND AIMS OF THE STUDY: When choosing a prosthetic replacement for a natural heart valve, one objective should be to minimize the workload placed on the heart. This workload can be raised by fluid mechanical energy losses imposed by the valve. For a patient with left ventricular hypertrophy, certain aortic valve types and orientations could be hemodynamically superior to others. METHODS: This study used a control volume analysis to investigate the effects of prosthetic mechanical aortic valve type and orientation on fluid mechanical energy losses in four in vitro models of the left ventricular outflow/aortic inflow tract in various degrees of hypertrophy. Flow visualization studies were performed to qualitatively validate this analysis. The two most commonly used mechanical valve designs were studied: the St. Jude Medical (SJM) bileaflet valve and the Medtronic Hall (MH) tilting disk valve. Experiments were performed in pulsatile flow at a constant heart rate of 60 beats per min for five valve type/orientation combinations. The stroke volume was varied between 40 and 120 ml in five increments for each model and valve/orientation studied. RESULTS: Valve type and orientation was found to have a significant effect on energy losses in these models (p < 0.05). Valve/orientation combinations with leaflets or disks approximately parallel to the proximal flow direction created lower energy losses than others. The MH valve in the 180 degrees orientation caused significantly less energy losses and pressure drops (orifice and recovered) than any of the SJM valve/orientations studied (p < 0.05). The SJM and MH valves in the 0 degree orientation were responsible for significantly more energy loss than other valve/orientations studied (p < 0.05). An aortic inflow tract model with severe (45 degrees) curvature created significantly more energy loss (p < 0.05) than those with less curvature (15 and 30 degrees). However, the insertion of an obstruction simulating a hypertrophic tissue outgrowth caused much more energy loss than increasing the severity of outflow tract curvature from 15 to 45 degrees. Both orifice pressure drop and recovered pressure drop had excellent linear correlations with energy losses found in these models. CONCLUSIONS: These results imply that: (i) prosthetic valve type and orientation should be considered when replacing the aortic valve of a hypertropic patient; (ii) removal of obstructions within the aortic inflow tract will decrease ventricular workload; and (iii) the Doppler-estimated pressure gradients commonly use by cardiologists to assess the performance of a prosthetic valve, correlate very well with left ventricular energy loss and work load.

Aortic Valve↗

Total cavopulmonary connection without the use of prosthetic material: technical considerations and hemodynamic consequences.

Total cavopulmonary connection with use of an autogenous intraatrial tunnel to create a straight tube between the inferior vena cava and the pulmonary artery was attempted in several types of cardiac anomaly in eight consecutive candidates for the Fontan operation. A small right atrium with an extraordinary location of the inferior vena cava and a short superior vena cava prevented the use of this procedure in two cases. By preserving the crista terminalis and the sinus node and its arteries we prevented the development of postoperative atrial arrhythmias in the short follow-up period, and the P trigger-signal averaged P waves were not different from those of other cardiac anomalies. The proximal stump of the superior vena cava was not incised in any case to enlarge the anastomosis, even when size mismatch between the superior and inferior venae cavae existed, as in a case of bilateral superior venae cavae. Stretching the vessels by approximately 150% was possible and permitted an adequate anastomosis. Cavopulmonary connections via the intraatrial tunnel ensured smooth, nonturbulent, somewhat pulsatile flow without a pressure gradient. We concluded that the creation of an autogenous intraatrial tunnel was possible in many cases without serious complications and that this procedure has potential benefit for the pulmonary circulation in the aspect of pulsatility.

Adult↗

Computational fluid dynamics simulations in realistic 3-D geometries of the total cavopulmonary anastomosis: the influence of the inferior caval anastomosis.

Fluid dynamics of Total Cavo-Pulmonary Connection (TCPC) were studied in 3-D models based on real dimensions obtained by Magnetic Resonance (MR) images. Models differ in terms of shape (intra- or extra-cardiac conduit) and cross section (with or without patch enlargement) of the inferior caval (IVC) anastomosis connection. Realistic pulsatile flows were submitted to both the venae cavae, while porous portions were added at the end of the pulmonary arteries to reproduce the pulmonary afterload. The dissipated power and the flow distribution into the lungs were calculated at different values of pulmonary arteriolar resistances (PAR). The most important results are: i) power dissipation in different TCPC designs is influenced by the actual cross sectional area of the IVC anastomosis and ii) the inclusion of a patch minimizes the dissipated power (range 4-13 mW vs. 14-56 mW). Results also show that the perfusion of the right lung is between 15% and 30% of the whole IVC blood flow when the PAR are evenly distributed between the right and the left lung.

Blood Flow Velocity↗

Peak velocity determination using fast Fourier velocity encoding with minimal spatial encoding.

For quantitative peak velocity determination, a technique was developed that uses Fourier velocity encoding (FVE) for the fast acquisition of images of velocity with no spatial encoding other than slice selection. The technique produces images of velocity versus temporal frequency. In applications where the quantity of interest is the peak velocity and in-plane spatial localization is not required, high SNR images are produced with reduced sensitivity to errors due to slice thickness and motion. The technique was validated using steady and pulsatile flow in a straight tube, and compared to both phase contrast measurements and numerical models using steady flow in a 50% and a 75% cosinusoidal stenosis phantom. Results show that for slices as large as 2 cm and/or undergoing periodic motion, FVE can accurately measure the peak velocity in cases where a distribution of velocities exist.

Blood Flow Velocity↗

A novel culture system shows that stem cells can be grown in 3D and under physiologic pulsatile conditions for tissue engineering of vascular grafts.

BACKGROUND: Currently available vascular grafts have been limited by variable patency rates, material availability, and immunological rejection. The creation of a tissue-engineered vascular graft (TEVG) from autologous stem cells would potentially overcome these limitations. As a first step in creating a completely autologous TEVG, our objective was to develop a novel system for culturing undifferentiated mouse embryonic stem cells (mESC) in a three-dimensional (3D) configuration and under physiological pulsatile flow and pressure conditions. MATERIALS AND METHODS: A bioreactor was created to provide pulsatile conditions to a specially modified four-well Labtek Chamber-Slide culture system. Undifferentiated mESC were either suspended in a 3D Matrigel matrix or suspended only in cell-culture media within the culture system. Pulsatile conditions were applied to the suspended cells and visualized by video microscopy. RESULTS: Undifferentiated mESC were successfully embedded in a 3D Matrigel matrix and could withstand physiological pulsatile conditions. Video microscopy demonstrated that the mESC in the 3D matrix were constrained to the wells of the culture system, moved in unison with the applied flows, and were not washed downstream; this was in contrast to the mESC suspended in media alone. CONCLUSIONS: Undifferentiated mESC can be grown in 3D and under pulsatile conditions. We will use these results to study the effects of long-term pulsatile conditions on the differentiation of mESC into endothelial cells, smooth muscle cells, and fibroblast cells with the long-term goal of creating a completely autologous TEVG.

Animals↗

Effects of an artery/vascular graft compliance mismatch on protein transport: a numerical study.

Small-diameter vascular graft failure by intimal hyperplasia and thrombosis may result from flow disturbances and disruption of chemical transport in the fluid at the distal anastomosis, because of compliance mismatch between the graft and host artery. In previous studies. lower-than-normal wall shear stress (WSS), particle trapping, and high particle residence times were observed at the distal anastomosis due to a pulsatile tubular expansion effect caused by nonuniform radial deformations. This study was undertaken to examine effects of compliance and radius mismatch on the distribution of a model protein released at the graft-fluid interface. Finite element simulations of end-to-end vascular grafting were performed under pulsatile flow, using fluid-structure coupling to give physiologic wall displacements. Results showed that protein is convected smoothly downstream in a uniform compliant tube. A compliance mismatch disturbed the transport, causing positive and negative gradients in the concentration profile at the distal anastomosis. This was seen when the graft and artery radii were matched at zero pressure and at mean arterial pressure; low WSSs were only observed in the former case. Thus the distal intimal hypertrophy seen in noncompliant grafts may be caused partly by decreased WSS, and partly by concentration gradients of dissolved chemicals affecting chemotaxis of cells.

Animals↗