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Thiopentone pharmacokinetics during cardiopulmonary bypass with a nonpulsatile or pulsatile flow.

To evaluate possible factors affecting the pharmacokinetics of thiopentone during cardiopulmonary bypass (CPB), the present study was undertaken in patients scheduled for coronary artery bypass grafting and with in vitro experiments. The effects of nonpulsatile and pulsatile flow during CPB on the distribution and elimination of thiopentone were compared in 30 patients anaesthetized with fentanyl. The initial rapid phases of distribution of thiopentone were studied in 17 patients undergoing a nonpulsatile or pulsatile perfusion, to whom thiopentone 6 mg/kg was given as a rapid intravenous bolus during CPB. In order to study later distribution and early elimination of thiopentone, 13 patients perfused with a nonpulsatile or pulsatile flow received 6 mg/kg of the drug as a 15-min intravenous infusion before CPB. No differences in the pharmacokinetic parameters characterizing distribution and elimination of thiopentone were found between the patients undergoing nonpulsatile or pulsatile perfusion. As measured in 10 of the patients receiving the drug before the institution of CPB, no difference in plasma thiopentone level was observed in blood samples drawn simultaneously from a radial arterial cannula and a pulmonary artery catheter before, during and after CPB. This suggests that thiopentone is not sequestered in lungs during CPB. In vitro binding of thiopentone to the CPB equipment was studied in 6 experiments using a closed circuit. After a 60-min circulation time, only 50% of the predicted thiopentone level was recovered from the perfusate. It is concluded that replacing a nonpulsatile perfusion with a pulsatile one has no effect on the distribution and elimination of thiopentone in patients undergoing CPB. During CPB, thiopentone is sequestered in the extracorporeal circuit but not in the lungs.

Adult↗

Structural details of boundary layer separation in a model human carotid bifurcation under steady and pulsatile flow conditions.

We have used a dye-flow visualization technique to analyze the substructure of flow separation in a plastic model of the human carotid bifurcation under steady and pulsatile flow. Under steady conditions at a physiologic flow split (Q external carotid/Q common carotid = 0.30) and Reynolds number (500), a large region of separated fluid developed along the outside wall of the sinus, opposite the flow divider. Yellow dye injected into the boundary layer upstream from the bifurcation traveled slowly along the wall of the common carotid and entered directly into the separation. Blue dye injected into the central, high-velocity streamlines in the common carotid impacted on the flow divider, then traveled circumferentially and entered the separation. Mixing of these two sources was documented by the appearance of green fluid, which lingered in the region of separation. Pulsatile flow resulted in a smaller region of separation; mixing still occurred. Flow separation at the carotid bifurcation is a site of mixing of fluids previously subjected to prolonged low-shear wall contact and brief high-shear wall contact. Separation is itself a site of low shear, but this study reveals a mechanism whereby low and high shear may act independently or synergistically to explain the link between flow separation and atherogenesis.

Carotid Arteries↗

The response of adult human saphenous vein endothelial cells to combined pressurized pulsatile flow and cyclic strain, in vitro.

Adult human saphenous vein endothelial cells (HVEC) were cultured in a compliant tubular device and evaluated by Northern hybridization for the effects of combined pressurized pulsatile flow and cyclic strain on the expression of mRNAs for endothelin-1 (ET-1), endothelial cell nitric oxide synthase (ecNOS), tissue plasminogen activator (tPA), and plasminogen activator inhibitor type 1 (PAI-1). The hemodynamic environment was designed to mimic shear stress conditions at the distal anastomosis of a saphenous vein graft, a common site of intimal proliferation. Steady-state mRNA levels in experimental tubes were expressed relative to that in controls. No changes were observed in ET-1 mRNA after 1 and 24 hr, but a 50% decrease in experimental cultures was observed after 48 hr in the vascular simulating device. Similar results were obtained for ecNOS mRNA, although a subgroup (4 of 11) showed a significant decrease (>50%) by 24 hr. For tPA mRNA, no change was observed after 1 hr, but a significant decrease (>60%) was measured after 24 hr and no message was detectable after 48 hr. Steady-state levels for PAI-1 mRNA remained unchanged through 48 hr of treatment. These results show that pressure, pulsatile flow, and cyclic strain, when applied in concert, differentially alter vasoactive and fibrinolytic functions in HVEC. Moreover, the dramatic decrease in steady-state levels of tPA mRNA is consistent with a shift toward an increased thrombotic state.

Adult↗

Cerebral metabolism and effects of pulsatile flow during retrograde cerebral perfusion.

We evaluated cerebral metabolism during retrograde cerebral perfusion (RCP) and circulatory arrest under profound hypothermia, and also investigated the effect of pulsatile flow on RCP. Eighteen adult mongrel dogs were placed on cardiopulmonary bypass and were cooled to a nasopharyngeal temperature of 20 degrees C. At this temperature, hypothermic circulatory arrest (HCA; n = 6), non-pulsatile RCP (NP-RCP; n = 6), and pulsatile RCP (P-RCP; n = 6) were performed for 60 minutes. Retrograde cerebral perfusion was performed via the bilateral internal maxillary veins, and retrograde flow rate was regulated to maintain a mean perfusion pressure of 20 mmHg in the external jugular vein. During RCP, the temperature was maintained in a narrow range, oxygen consumption and carbon dioxide excretion could be observed, the excess lactate was maintained at a negative value, and cerebral tissue ATP concentration was significantly higher than in the HCA group. The cerebral tissue water content was significantly lower in the P-RCP group than in the NP-RCP group. These findings suggest that hypothermia of the central nervous system, the supply of oxygen, the excretion of metabolites, aerobic metabolism, and the cerebral ATP level were maintained by RCP. In conclusion, RCP may possibly provide adequate metabolic support for the brain during total circulatory arrest, and pulsatile flow appears to reduce cerebral edema when compared with non-pulsatile flow in dogs.

Adenosine Triphosphate↗

Numerical study of nonlinear pulsatile flow in S-shaped curved arteries.

The nonlinear pulsatile blood flow in S-shaped curved arteries was studied with finite element method. Numerical simulations for flows in two models of S-shaped curved arteries with different diameters and under the same boundary conditions were performed. The temporal and spatial distributions of hemodynamic variables during the cardiac cycle such as velocity field, secondary flow, pressure, and wall shear stresses in the arteries were analyzed. Results of numerical simulations showed that the secondary flow in the larger S-shaped curved artery is more complex than that in the smaller one; stronger eddy flow occurred in the inner bends of curved arteries; pressure and wall shear stresses changed violently in the curved arteries, especially in the larger model. These hemodynamic variables in curved arteries will cause important effects on the function of arterial endothelium in the region. For instance, they may lead to the proliferation of smooth muscle cells and the thickening of the intima, and cardiovascular diseases such as atherosclerosis may develop in such regions. Due to having the special blood flow characteristics in the S-shaped arteries, it is worthwhile to study flow in this kind of curved artery. The comprehensive theoretical foundation showed in the present study can be extended to approach problems of nonlinear pulsatile flow in curved arteries with more complex geometrical shape.

Animals↗

A model based on dimensional analysis for noninvasive quantification of valvular regurgitation under confined and impinging conditions: in vitro pulsatile flow validation.

A technique is proposed for the noninvasive quantification of regurgitant flows under confined and impinging conditions. Its use requires only the knowledge of the jet orifice velocity, receiving chamber diameter, orifice-to-end wall distance and any downstream jet centerline velocity at a known distance from the orifice. The technique is based on dimensional analysis and provides a prediction of peak regurgitant flow rates. To validate the technique, known physiologic pulsatile flows were pumped through 2- and 4-mm circular orifices at 70 to 150 beats/min, into two different receiving chambers of 51 and 88 mm in diameter. At each heart rate, the peak orifice velocity was varied from 2 to 5 m/s, and the orifice-to-end wall distance was varied from 30 to 93 mm. Centerline velocities were recorded by pulsed Doppler ultrasound and averaged over multiple beats. A dimensional analysis of the parameters of the study provided an equation relating normalized centerline velocity to orifice-to-end wall distance, chamber diameter and downstream location. Statistical modeling of the experimental data was performed to compute the constants involved in this equation. The estimated (i.e., predicted by the technique) peak regurgitant flow rates were found to fall within 10% of the actual values, when centerline velocities were measured over a range of centerline distances from six orifice diameters to 85% of the chamber length. Therefore, the proposed technique provides, for the first time, a quantitative method for calculating valvular regurgitant flow rates under confined and impinging conditions.

Blood Flow Velocity↗

Release of endothelium-derived relaxing factor is modulated both by frequency and amplitude of pulsatile flow.

We have dissociated the effects of frequency and amplitude of pulsatile flow on flow-induced release of endothelium-derived relaxing factor (EDRF) using cascade bioassay. Rat aortic segments were buffer perfused with a peristaltic pump at a constant mean flow rate of 9 ml/min. EDRF activity in effluent was measured by relaxation of endothelium-denuded rabbit aortic rings preconstricted by phenylephrine. Pulse frequency was varied over the range 0.1-12 Hz at a constant amplitude of 2 mmHg; pulse amplitude was varied over the range 2-16 mmHg at a constant frequency of 0.1 Hz. Relaxation of the detector vessel depended on frequency of flow through the donor; peak response occurred between 4.2 and 6 Hz and was approximately three times greater than that induced at lower or higher frequencies. In contrast, increases in pulse pressure amplitude (maximum 16 mmHg) monotonically augmented constriction of partially preconstricted detector tissue by up to 10%. Incubation of the donor vessel with NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthesis, or removal of its endothelium by rubbing, abolished both the frequency- and the amplitude-dependent effects observed in the detector tissue, indicating that these were mediated by changes in EDRF release. Increasing the amplitude of the pressure pulse also reduced mean perfusion pressure (by up to 50%), implying distension of donor vessel since mean flow rate was constant. This fall in pressure was not affected by incubation with L-NAME or removal of endothelium, indicating that it was not dependent on EDRF activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Pulsatile flow computational simulations of mitral regurgitation.

The noninvasive quantification of mitral regurgitation remains an important clinical goal. Recently, the flow convergence method was developed to estimate the regurgitant flow rate. This study used three-dimensional pulsatile flow computational simulations to evaluate the accuracy of the flow convergence method in the presence of complicating factors such as ventricular confinement, noncircular orifice shape, and the presence of aortic outflow. Results showed that in the absence of aortic outflow and ventricular confinement, there was a plateau zone where the calculated flow rate by the hemispheric formula approximated the true flow rate, independent of the orifice shape. In the presence of aortic outflow and in chambers of physiologic dimensions, there was no longer a clear zone where the hemispheric formula was valid. The hemi-elliptic modification of the flow convergence method worked in all cases, independent of the degree of ventricular confinement or the presence of aortic outflow. Therefore, application of the hemi-elliptic formula should be considered in future clinical studies.

Aorta↗

Platelet near-wall excess in porcine whole blood in artery-sized tubes under steady and pulsatile flow conditions.

Platelet margination (enhanced platelet concentration in the near wall region of a blood vessel) has been well documented in small vessels. In artery-sized vessels margination has only been demonstrated in one study, using ghost cell suspensions and under relatively non-physiologic conditions of steady flow and 50 cm development length. Local sampling experiments were performed to confirm platelet margination in artery-sized stainless steel tubes, for a typical anatomical length and under pulsatile flow, using fresh EDTA-anticoagulated porcine whole blood (N=21). Experiments were designed using three-dimensional Computational Fluid Dynamics (CFD) to model the sample region with greater fidelity. Steady flow experiments in 50 cm long tubes verify published laser Doppler measurements of platelet margination in 3 mm ID tubes at normal arterial shear rate (500 s(-1). Margination persists under pulsatile flow conditions (63.8 pulses/min), but in steady flow at length of 10 cm, margination is reduced. Platelet margination ratio (the ratio of the platelet concentration near the wall to bulk average platelet count) ranges from 1.21 to 2.48. No significant effects of calculated sampling thickness (20 microm and 50 microm) or pulsatility were detected. Hematocrit margination ratio is 0.68 to 0.90. Two model platelet concentration profiles are fit to the experimental results.

Animals↗

Pulsatile vs. non-pulsatile flow during cardiopulmonary bypass. A comparison of early postoperative changes.

The aim of the study was to evaluate possible haemodynamic and metabolic effects of pulsatile flow in cardiopulmonary bypass. The subjects were 20 patients undergoing coronary artery bypass grafting. They had no complicating diseases. Ten consecutive patients with pulsatile perfusion were compared with ten consecutive patients with non-pulsatile perfusion. The haemodynamic parameters, chest X-rays, fluid balance and changes in circulating thrombocytes were unaffected by adding pulsatile flow to cardiopulmonary bypass. The arterial-venous oxygen content difference and intrapulmonary shunting were also unaffected. Whole-body oxygen consumption was higher in the pulsatile group immediately after bypass, but subsequently there were no differences. The haemoglobin and haematocrit values were higher in the non-pulsatile group two hours postoperatively, but did not differ in the rest of the observation period. The clinical course was similar in the two groups.

Blood Circulation↗

Decrease in pulsatile flow in the anterior cerebral arteries in infantile hydrocephalus.

The effect of ventriculomegaly with or without elevated intracranial pressure (ICP) on pulsatile flow in the anterior cerebral artery has been studied by a noninvasive Doppler technique in 11 infants with hydrocephalus. The cause of hydrocephalus was intraventricular hemorrhage in nine infants, Arnold-Chiari malformation in one, and bacterial meningitis in one. The pulsatility index (PI) (inversely related to pulsatile flow) was calculated from the systolic and diastolic amplitudes of flow in the anterior cerebral artery. All 11 patients with elevated PI had marked ventriculomegaly, and all but two had raised ICP. Four patients with massive ventriculomegaly and elevated ICP had maximal PI (ie, 1.00). The finding of elevated PI with ventriculomegaly and normal ICP, observed in two patients, suggested that ventriculomegaly is a more critical factor than ICP in the pathogenesis of the impaired flow. Treatment of ventriculomegaly in seven patients resulted in a decrease in PI. Of the four untreated patients, three died and one was not available for further study. Compromised flow in the anterior cerebral artery may be a sensitive barometer of impending ischemic injury with evolving ventriculomegaly, particularly following intraventricular hemorrhage. The PI may be a valuable parameter for the study of the mechanism of brain injury and for determination of optimal timing of corrective intervention.

Cerebral Arteries↗

Doppler-ultrasonographic detection of retrograde pulsatile flow in the caudal vena cava of a puppy with cor triatriatum dexter.

A three-month-old puppy had ascites, but its heart was normal by auscultation. Abdominal ultrasonography revealed an enlarged liver, distended hepatic veins and a distended caudal vena cava. Doppler ultrasonography detected retrograde flow in the caudal vena cava and abnormally pulsatile flow in the hepatic veins and caudal vena cava. A non-selective venogram was used to detect the path of the blood from the caudal vena cava. A postmortem examination showed that the puppy had cor triatriatum dexter and a defect in the atrial septum.

Animals↗

Changes in ultrasonic Doppler backscattered power downstream of concentric and eccentric stenoses under pulsatile flow.

The main objective of the present work was to investigate, under pulsatile flow, the patterns of variation of the Doppler power backscattered by blood and Sephadex particles upstream and downstream of concentric and eccentric stenoses ranging from 47% to 91% area reduction. Doppler measurements were performed at 5 diameters upstream and 5, 10, 15 and 20 diameters downstream of the constriction. For the concentric 75% and 85%, and the eccentric 79% and 91% area reduction stenoses, a progressive increase of the power backscattered by red cell suspensions at 40% hematocrit was measured downstream of the narrowing. The maximal power usually occurred around 10 diameters after the stenosis and dropped further downstream. In addition to the increase in the power, a cyclic variation of the backscattered intensity was observed within the flow cycle. For the concentric 52% and eccentric 47% area reduction stenoses, no variation of the Doppler power was measured during flow acceleration and deceleration for all recording sites. A coefficient of correlation of 0.82 was measured between the percentage of area reduction and the ratio of the Doppler mean power at 10 diameters downstream to that at 5 diameters upstream of the stenoses. Using Sephadex particles at low concentration, no increase of the Doppler power was found downstream of the 85% and 91% area reduction stenoses. The possible link between the intensity of turbulence and the power backscattered by blood is discussed along with the influence of the correlation between the scattering particles, under turbulent flow.

Acceleration↗

The importance of flow pulsatility for the rate of transvascular fluid filtration in lungs.

1. The rate of transvascular fluid filtration has been studied with a gravimetric technique in isolated perfused rabbit lungs during periods of elevated left atrial pressure (PLA). 2. Fluid filtration was expressed as the filtration coefficient, Kf (g/min x 100 g bloodless lung x mmHg PLA) and determined during alternately pulsatile and non-pulsatile perfusion in six zone III and three zone II/I lung preparations. Perfusion pattern was changed without interruption of flow. Mean in- and outflow pressures were kept constant. 3. In all the lungs it was found that Kf was higher during pulsatile than during non-pulsatile flow (P less than 0.01). Mean Kf (+/- S.E. of mean) for the zone III preparations was 0.42 (+/- 0.089) and 0.27 (+/- 0.057) for pulsatile and non-pulsatile perfusion, respectively. The corresponding figures for the zone II/I preparations were 0.11 (+/- 0.035) and 0.04 (+/- 0.030). 4. We suggest that the difference is due to a larger filtration area and/or a higher mean microvascular hydrostatic pressure during pulsatile than during non-pulsatile flow and not to a rise in hydraulic conductivity due to pressure pulsations ('stretched pores'). 5. When the water-exchange function of the lung is considered, flow pattern should be taken into account as an entity in its own right in addition to the steady state or the mean component of blood flow.

Animals↗

Measurement of pulsatile flow using MRI and a Bayesian technique of probability analysis.

This work shows that complete spatial information of periodic pulsatile fluid flows can be rapidly obtained by Bayesian probability analysis of flow encoded magnetic resonance imaging data. These data were acquired as a set of two-dimensional images (complete two-dimensional sampling of k-space or reciprocal position space) but with a sparse (six point) and nonuniform sampling of q-space or reciprocal displacement space. This approach enables more precise calculation of fluid velocity to be achieved than by conventional two q-sample phase encoding of velocities, without the significant time disadvantage associated with the complete flow measurement required for Fourier velocity imaging. For experimental comparison with the Bayesian analysis applied to nonuniformly sampled q-space data, a Fourier velocity imaging technique was used with one-dimensional spatial encoding within a selected slice and a uniform sampling of q-space using 64 values of the pulsed gradients to encode fluid flow. Because the pulsatile flows were axially symmetric within the resolution of the experiment, the radial variation of fluid velocity, in the direction of the pulsed gradients, was reconstructed from one-dimensional spatial projections of the velocity by exploiting the central slice theorem. Data were analysed for internal consistency using linearised flow theories. The results show that nonuniform q-space sampling followed by Bayesian probability analysis is at least as accurate as the combined uniform q-space sampling with Fourier velocity imaging and projection reconstruction method. Both techniques give smaller errors than a two-point sampling of q-space (the conventional flow encoding experiment).

Bayes Theorem↗

An experiment on the pulsatile flow at transitional Reynolds numbers--the fluid dynamical meaning of the blood flow parameters in the aorta.

An experiment on the fully developed sinusoidal pulsatile flow at transitional Reynolds numbers was performed to evaluate the basic characteristics of the wall shear stress. In this experiment, the wall shear stress was calculated from the measured section averaged axial velocity and the pressure gradient by using the section averaged Navier-Stokes equation. The experimental results showed that the ratio of the amplitude of the wall shear stress to the amplitude of the pressure gradient had the maximum value when the time averaged Reynolds number was about 4000 and the Womersley number was about 10. As this condition is close to the blood flow condition in the human aorta, it is suggested that the parameter of the aorta has an effect to increase the amplitude of the wall shear stress acting on the arterial wall.

Aorta↗

Numerical simulation of opening process in a bileaflet mechanical heart valve under pulsatile flow condition.

BACKGROUND AND AIM OF THE STUDY: Most previous computational fluid dynamics (CFD) studies of blood flow in mechanical heart valves (MHVs) have not efficiently addressed the important features of moving leaflet and blood-leaflet interaction. Herein, computationally efficient approaches were developed to study these features and to obtain better insight into the pulsatile flow field in bileaflet MHVs. METHODS: A simple and effective method to track the moving boundary was proposed, and an efficient method for calculating the blood-leaflet interaction applied. In this way, a CFD code was developed to study the pulsatile flow field around bileaflet MHVs. The CFD code was parallelized on a supercomputer to reduce turn-around time in the simulation. The solver was then used to study the opening process in a St. Jude Medical (SJM) size 29 bileaflet MHV. RESULTS: CFD results showed that, in the opening process, the flow field was consistently partitioned into two side channels and a central channel due to the presence of the two leaflets. In the flow field near the surface of the two leaflets, the fluid velocity followed the local surface velocity of the leaflets, thus showing a strong blood-leaflet interaction effect. Throughout the valve-opening process, peak velocities were always observed near the tips of the valve leaflet. The CFD simulation showed that the opening process took approximately 0.044 s, which compared well with experimental findings. CONCLUSION: The new computational approaches were efficient and able to address the moving leaflet and blood-leaflet interaction. The flow field in the opening process of a SJM 29 bileaflet MHV was successfully simulated using the developed solver.

Blood Flow Velocity↗

Three-dimensional numerical analysis of pulsatile flow and wall shear stress in the carotid artery bifurcation.

To analyse the pulsatile flow field and the mechanical stresses in a three-dimensional carotid artery bifurcation model, computer simulation is applied. The approximation of the Navier-Stokes equations uses a pressure correction finite element method. Numerical results are presented for axial and secondary flow velocity and wall shear stresses with special emphasis on the fluid dynamics in the carotid sinus. This region is of major interest because it is affected preferentially by lesions. Detailed local flow studies as carried out here should lead to a further insight into the mechanisms of atherogenesis. The flow conditions used in the study were chosen according to Ku et al. (Arteriosclerosis 5, 293-302, 1985). The results of this numerical analysis agree in the essential features with their experimental results.

Blood Flow Velocity↗