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Cerebral microcirculatory changes in rat with a cardiopulmonary bypass using fluorescence videomicroscopy.

Cerebral microcirculatory changes in rat with a cardiopulmonary bypass (CPB) at normothermia was investigated in relation to cerebrovascular disorders caused by surgical operation with CPB. The mean arterial pressure was changed from 50 to 200 mmHg by changing the pump flow-rate. A non-pulsatile flow model was developed by stopping the cardiac beat using a fibrillator. The pial microcirculation was visualized using fluorescence-labeled red cells and dextran, and was directly observed under a fluorescence videomicroscope during CPB. Based on the recorded videoimages, the arteriolar diameter and red cell velocity were measured, in which single arterioles with approximately 40 microm diameter were selected among the pial arterioles. It was shown that when the arterial pressure was changed: (1) arteriolar vasodilation or constriction appeared during pulsatile flow but it disappeared during non-pulsatile flow, and (2) the arteriolar red cell velocity increased or decreased linearly during non-pulsatile flow as well as pulsatile flow. The flow-rate was almost constant at a large range of the mean arterial pressure from 60 to 160 mmHg during pulsatile flow (autoregulation), but it increased or decreased during non-pulsatile flow with an increase or decrease in mean arterial pressure, respectively. It was suggested that pulsativity might be responsible for cerebral autoregulation.

Animals↗

Pulsatile blood flow, shear force, energy dissipation and Murray's Law.

BACKGROUND: Murray's Law states that, when a parent blood vessel branches into daughter vessels, the cube of the radius of the parent vessel is equal to the sum of the cubes of the radii of daughter blood vessels. Murray derived this law by defining a cost function that is the sum of the energy cost of the blood in a vessel and the energy cost of pumping blood through the vessel. The cost is minimized when vessel radii are consistent with Murray's Law. This law has also been derived from the hypothesis that the shear force of moving blood on the inner walls of vessels is constant throughout the vascular system. However, this derivation, like Murray's earlier derivation, is based on the assumption of constant blood flow. METHODS: To determine the implications of the constant shear force hypothesis and to extend Murray's energy cost minimization to the pulsatile arterial system, a model of pulsatile flow in an elastic tube is analyzed. A new and exact solution for flow velocity, blood flow rate and shear force is derived. RESULTS: For medium and small arteries with pulsatile flow, Murray's energy minimization leads to Murray's Law. Furthermore, the hypothesis that the maximum shear force during the cycle of pulsatile flow is constant throughout the arterial system implies that Murray's Law is approximately true. The approximation is good for all but the largest vessels (aorta and its major branches) of the arterial system. CONCLUSION: A cellular mechanism that senses shear force at the inner wall of a blood vessel and triggers remodeling that increases the circumference of the wall when a shear force threshold is exceeded would result in the observed scaling of vessel radii described by Murray's Law.

Blood Flow Velocity↗

A novel pulsatile, laminar flow bioreactor for the development of tissue-engineered vascular structures.

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.

Bioreactors↗

Pulsatile poststenotic flow studies with laser Doppler anemometry.

The pulsatile flow field distal to axisymmetric constrictions in a straight tube was studied using laser Doppler anemometry. The upstream centerline velocity waveform was sinusoidal at a frequency parameter of 7.5 and mean Reynolds number of 600. Stenosis models of 25, 50 and 75% area reduction were employed and velocity data were derived by ensemble averaging methods. Extensive measurements of the pulsatile velocity profiles are reported, and wall shear rates were computed from the near wall velocity profile gradients. The experiments indicate that a permanent region of poststenotic flow separation does not exist even for the severest constriction, in contrast to results for steady flow. Values of wall shear stress were greatest near the throat of the constriction and were relatively low in the poststenotic region, including the region of most intense flow disturbance. Turbulence was found only for the 75% stenosis model and was created only during a segment of the cycle. Although much emphasis has been placed upon turbulence in the detection of arterial stenoses, particularly as identified by Doppler ultrasound spectral broadening, the present study implies that identification of flow disturbances of an organized nature may be more fundamental in recognizing mild to moderate disease. Additionally, the relationship of these flow field results to the animal aortic coarctation model often employed in atherogenesis studies is discussed.

Arteries↗

Effects of pulsatile and non-pulsatile perfusion on the isolated canine heart.

Isolated canine hearts with a critical stenosis on one coronary artery were perfused for 2 h with blood from supporting dogs using a new roller pump system that can deliver pulsatile or non-pulsatile flow perfusion. Non-pulsatile perfusion caused a decrease in coronary venous oxygen tension of 22% (P less than 0.05) accompanied by increasing carbon dioxide tension of 50% (P less than 0.02). With pulsatile flow coronary venous oxygen and carbon dioxide tensions remained stable. Non-pulsatile perfusion decreased the coronary arteriovenous oxygen difference by 35% (P less than 0.02), coronary blood flow by 40% (P less than 0.02), and myocardial oxygen consumption by 54% (P less than 0.01) whereas pulsatile flow did not change any of these variables. Subendocardial blood flow distal to the stenosis fell by 0.15 +/- 0.04 ml/min per gram myocardium (mean +/- S.E.M.) (P less than 0.01) during linear perfusion. The endocardial/epicardial-flow ratio was less than one and decreased further during fibrillation period indicating underperfusion of the endocardial muscle region. With pulsatile flow subendocardial flow remained unaltered during the two hours of fibrillation. Edema formation was 24% in hearts subjected to non-pulsatile flow but only 14% in hearts perfused by pulsatile perfusion (P less than 0.05). Accordingly, the ischemic area involved 40% of the left ventricle during non-pulsatile flow but 25% of the left ventricle in hearts perfused by pulsatile perfusion (P less than 0.05). The results indicate that pulsatile flow perfusion may prevent severe hemodynamic, hematologic, and metabolic alterations in fibrillating isolated canine hearts. It is suggested that pulsatile perfusion may be useful for fibrillating hearts during open heart surgery.

Animals↗

Finite element analysis of nonlinear pulsatile suspension flow dynamics in blood vessels with aneurysm.

A nonlinear pulsatile suspension flow in a dilated vessel is numerically analysed. Two sets of highly coupled nonlinear partial differential equations governing the suspension flow are numerically solved, to simulate the suspension flow dynamics. A transient velocity-pressure (UVP) finite element method (FEM) and a stable time integration scheme, based on a predictor-corrector strategy, with constant error monitoring are employed in the flow analysis. The pulsatile suspension flow is characterized by analysing the flow, pressure and stress fields. Effects of the nonlinear particulate phase on the nonlinear suspending fluid phase are brought out by comparing the suspension flow results with those of homogeneous flow. Particles are seen to dampen the flow velocity, wall and central axis pressure, pressure gradient and wall shear stress. time-dependent recirculation regions which are sensitive to the presence of particles are seen in the dilated portion of the vessel. These recirculation regions favour thrombogenesis. The nonlinear effects due to the vessel geometry and those due to the convective terms dominate the dampening effect of the particles. These nonlinear effects are depicted through the transverse velocity and pressure plots. Wall shear stresses of suspension flow are not only high but also alternate in direction.

Algorithms↗

Pulsatile blood flow in the entire coronary arterial tree: theory and experiment.

The pulsatility of coronary circulation can be accurately simulated on the basis of the measured branching pattern, vascular geometry, and material properties of the coronary vasculature. A Womersley-type mathematical model is developed to analyze pulsatile blood flow in diastole in the absence of vessel tone in the entire coronary arterial tree on the basis of previously measured morphometric data. The model incorporates a constitutive equation of pressure and cross-section area relation based on our previous experimental data. The formulation enables the prediction of the impedance, the pressure distribution, and the pulsatile flow distribution throughout the entire coronary arterial tree. The model is validated by experimental measurements in six diastolic arrested, vasodilated porcine hearts. The agreement between theory and experiment is excellent. Furthermore, the present pulse wave results at low frequency agree very well with previously published steady-state model. Finally, the phase angle of flow is seen to decrease along the trunk of the major coronary artery and primary branches toward the capillary vessels. This study represents the first, most extensive validated analysis of Womersley-type pulse wave transmission in the entire coronary arterial tree down to the first segment of capillaries. The present model will serve to quantitatively test various hypotheses in the coronary circulation under pulsatile flow conditions.

Animals↗

Turbulence detection in a stenosed artery bifurcation by numerical simulation of pulsatile blood flow using the low-Reynolds number turbulence model.

The pulsatile blood flow in a partially blocked artery is significantly altered as the flow regime changes through the cardiac cycle. This paper reports on the application of a low-Reynolds turbulence model for computation of physiological pulsatile flow in a healthy and stenosed carotid artery bifurcation. The human carotid artery was chosen since it has received much attention because atherosclerotic lesions are frequently observed. The Wilcox low-Re k-omega turbulence model was used for the simulation since it has proven to be more accurate in describing transition from laminar to turbulent flow. Using the FIDAP finite element code a validation showed very good agreement between experimental and numerical results for a steady laminar to turbulent flow transition as reported in a previous publication by the same authors. Since no experimental or numerical results were available in the literature for a pulsatile and turbulent flow regime, a comparison between laminar and low-Re turbulent calculations was made to further validate the turbulence model. The results of this study showed a very good agreement for velocity profiles and wall shear stress values for this imposed pulsatile laminar flow regime. To explore further the medical aspect, the calculations showed that even in a healthy or non-stenosed artery, small instabilities could be found at least for a portion of the pulse cycle and in different sections. The 40% and 55% diameter reduction stenoses did not significantly change the turbulence characteristics. Further results showed that the presence of 75% stenoses changed the flow properties from laminar to turbulent flow for a good portion of the cardiac pulse. A full 3D simulation with this low-Re-turbulence model, coupled with Doppler ultrasound, can play a significant role in assessing the degree of stenosis for cardiac patients with mild conditions.

Blood Flow Velocity↗

Hemodynamic effects of bidirectional cavopulmonary shunt with pulsatile pulmonary flow.

The effects of "pulsatile" bidirectional cavopulmonary shunt (BCPS) produced by the flow from the ventricle or Blalock-Taussig (B-T) shunt on ventricular function and pulmonary circulation were evaluated in 10 patients with univentricular heart from 3 to 37 months (mean, 16.6 +/- 9.5 months) after surgery. Age at operation ranged from 7 months to 15 years (mean, 5.5 +/- 4.5 years). In addition to the BCPS, pulmonary flow was supplied from a B-T shunt on the contralateral side of the BCPS in five patients, from the ventricle through the stenotic pulmonary valve in four patients, and from both the ventricle and a B-T shunt in one patient. There were no operative deaths; however, there were two late deaths from acute respiratory infection 10 and 13 months after operation. Mean pulmonary arterial pressure measured the first day after operation ranged from 10 to 19 mm Hg (mean, 14 +/- 3 mm Hg). Mean pulmonary arterial pressure at postoperative cardiac catheterization was less than 15 mm Hg (mean, 12 +/- 4 mm Hg). Pulse pressure ranged from 3 to 12 mm Hg (mean, 7 +/- 4 mm Hg). Arterial oxygen saturation increased significantly from 77 +/- 5% before BCPS to 86 +/- 4% immediately after discharge from the intensive care unit (p less than 0.005) and 85 +/- 3% (p less than 0.025) at late cardiac catheterization. Pulmonary arteriovenous fistula was not detected in contrast echocardiography and pulmonary arteriography. Systemic ventricular end-diastolic volume index decreased significantly (p less than 0.01) from 141 +/- 54 ml/m2 before BCPS to 98 +/- 35 ml/m2 1 month after BCPS by echocardiography.(ABSTRACT TRUNCATED AT 250 WORDS)

Anastomosis, Surgical↗

New version of flow-transformed pulsatile total artificial heart with no electrical switching valve.

The flow-transformed pulsatile total artificial heart (FTPTAH) is a new pulsatile total artificial heart that consists of a single continuous flow rotary blood pump and blood flow switching valves. It can perfuse the pulmonary and the systemic circulation alternately with pulsatile flow. A new version of the FTPTAH, which consists of one undulation pump (UP), 4 jellyfish valves, and a compensatory chamber, has been proposed. The UP is a reversible continuous flow blood pump, and flow transformation is caused by switching the direction of the motor rotation so that no electrical flow switching valve is needed. A prototype model could perfuse alternately pulmonary and systemic circulation with 3.0 L/min in a mock circulation. Unoxygenated blood in the UP at the end of pulmonary circulation will be stored in the compensatory chamber by shifting a flexible membrane to the direction of the left atrium (LA); therefore, the blood is not sent to the systemic circulation.

Atrial Function↗

The vibration of an artery-like tube conveying pulsatile fluid flow.

A hybrid method for investigating pulsatile fluid flow in a long, thin, artery-like tube subjected to external excitations is presented. The non-linear partial differential equations governing the motion of the system, which incorporate the influence of circumferential strains, are solved by a combination of a finite element method, a finite difference method and a method of characteristics with interpolation. An initially axially stretched elastic tube conveying pulsating fluid, simply supported at both ends, is modelled to assess the effect of external harmonic excitation on the dynamic responses of the tube and the fluid flow. The results agree well with new experimental data. Comparison of the predicted results with those of a decoupled model demonstrates that it is necessary to consider the mechanism of fluid-structure interaction fully in the study of initially stretched cylindrical tubes conveying pulsatile fluid flow. An analysis of these coupling effects is presented for Womersley numbers alpha = 2.81 and 3.97 and a mean flow Reynolds number Re = 875.

Aorta↗

Bidirectional cavopulmonary shunt with right ventricular outflow patency: the impact of pulsatility on pulmonary endothelial function.

OBJECTIVE: Although in vitro studies have suggested the importance of flow pulsatility in endothelial function, few reports have focused on pulmonary endothelial function under decreased pulsatile flow after a bidirectional cavopulmonary shunt with or without an additional pulmonary flow source. The purpose of the present study was to assess the pulmonary endothelial function after bidirectional cavopulmonary shunt. METHODS AND RESULTS: Pulmonary vasodilating response was evaluated in 10 patients 0.4 to 7.0 years (median 1.6 years) after bidirectional cavopulmonary shunt who were provided an additional flow source by retaining the pulmonary outflow tract and in 8 control subjects. Average pulmonary flow velocity was measured with a Doppler flow wire placed in the segmental lower lobe pulmonary artery during incremental infusion of acetylcholine (10(-8), 10(-7), 10(-6), and 10(-5) mol/L) and then of nitroglycerin (0.5 and 1.0 microg. kg(-1). min(-1)) after recovery. In the control subjects, a dose-dependent increase in flow velocity was observed in response to acetylcholine (maximum increase was 155% +/- 17% of baseline) and to nitroglycerin (maximum increase was 151% +/- 20% of baseline). In contrast, patients showed a significantly impaired response to acetylcholine (maximum increase was 124% +/- 17% of baseline; P <.01 vs control), whereas the response to nitroglycerin was preserved (138% +/- 12% of baseline; P =.09 vs control). In addition, the maximum response to acetylcholine correlated significantly with the pulmonary pulse pressure (r = 0.89, P <.01) and with the pulmonary flow pulsatility (r = 0.88, P <.01). CONCLUSIONS: These results clearly suggest that patients after bidirectional cavopulmonary shunt show pulmonary endothelial functional attenuation and, of more importance, that decreased pulsatility of cavopulmonary flow is mainly responsible for this endothelial abnormality.

Acetylcholine↗

Magnetic resonance phase velocity mapping through NiTi stents in a flow phantom model.

PURPOSE: To assess constant and pulsatile flow velocity within the lumen of a peripheral NiTi stent using phase velocity mapping for comparison with independent assessments of flow velocity in a phantom model. MATERIALS AND METHODS: A 9 x 20-mm stent installed in flexible tubing was placed in a phantom filled with stationary fluid. Constant and pulsatile flow (produced by a pump programmed to produce a simulation of the carotid artery flow) was assessed using phase velocity mapping at 4.1 T (for constant flow) and at 1.5 T (for pulsatile flow). In all cases 256 x 256 gradient echo phase velocity maps were acquired. For the pulsatile flow condition, cine images with acquisition gated to the pump cycle were acquired with 40 msec temporal resolution across the simulated cardiac cycle. Computed flow volume rates were compared with fluid volume collection for the constant flow model, and with ultrasonic Doppler flow meter measurements for the pulsatile model. RESULTS: The data showed that volume flow rate assessments by phase velocity mapping agreed with independent measurements within 10% to 15%. CONCLUSION: Phase velocity mapping of the lumen of peripheral size NiTi stents is possible in an in vitro model.

Alloys↗

Flow-induced release of EDRF in the pulmonary vasculature: site of release and action.

Pulsatile flow is thought to lower pulmonary vascular resistance by passive recruitment of capillaries and by active vasodilation. This study was undertaken to investigate the role of endothelium-derived relaxing factor (EDRF) during pulsatile flow in isolated canine left lower lobes pretreated with indomethacin. The lobes were perfused in situ with autologous blood (approximately 500 ml/min) using a nonpulsatile pump (Masterflex) or a pulsatile pump (Harvard). With the occlusion techniques, vascular resistance was partitioned into four segments: arterial (Ra), small arterial (R'a), small venous, and venous (Rv). Pulsatile flow (frequency = 70 min-1) did not lower total vascular resistance during baseline or during vasoconstriction. Distribution of vascular resistance among the four segments was not altered significantly by pulsatile flow during normoxia and angiotensin. In contrast, switching to pulsatile flow during hypoxia was associated with an increase in Ra and a decrease in R'a and Rv. N omega-nitro-L-arginine (L-NNA) had no effect on total or segmental resistance during baseline conditions but potentiated the hypoxic pressor response and prevented its recovery by 50%. In addition, the reduction in R'a by pulsatile flow was attenuated by L-NNA, suggesting that EDRF is released by pulsatile flow in this segment. We conclude that a shear stress-induced EDRF release from the small arteries is present in canine lungs and is experimentally demonstrable during pulsatile flow and hypoxia.

Angiotensin II↗

Analysis of pulsatile blood flow: a carotid siphon model.

Numerical results for axial and secondary flow velocity and pressure in a three-dimensional model of the human carotid siphon have been calculated; the investigations were carried out under physiologically relevant pulsatile flow conditions. Time-dependent, three-dimensional Navier-Stokes equations were solved numerically by using a special finite element method. The results of the computer simulation presented here concentrate on the secondary motion effect during the pulsatile flow cycle in multiple three-dimensional curvatures.

Blood Flow Velocity↗

Linear and nonlinear analyses of pulsatile blood flow in a cylindrical tube.

A non-Newtonian shear-thinning constitutive relation is proposed to study pulsatile flow of whole blood in a cylindrical tube. The constitutive relation, which satisfies the principle of material frame indifference, is derived from viscometric data obtained from whole blood over a range of hematocrits. Assuming axisymmetric flow in a rigid cylindrical tube of constant diameter, a second-order, nonlinear partial differential equation governing the axial velocity component is obtained. Imposing a periodic pressure gradient, the governing equation was solved numerically using finite difference methods over a range of Stokes values and hematocrits. For a forcing frequency of 1 Hz, results are presented over tube diameters ranging between 0.1 and 2 cm and over hematocrits ranging between 10 and 80%. For a given hematocrit, velocity profiles predicted for the non-Newtonian model under sinusoidal forcing reveal attenuated volume flow rate and enhanced vorticity transport over the tube cross-section relative to a Newtonian fluid having a viscosity corresponding to the high shear-rate limit. For moderate to high Stokes numbers, consistent with flow in large arteries, our results revealed a viscosity distribution that was nearly time invariant. An analytic solution was obtained for a fluid having arbitrarily prescribed radially varying, temporally invariant viscosity and density distributions under arbitrary periodic pressure forcing. Close agreement was observed between our numerical and analytical results when the imposed viscosity distribution was chosen to approximate the time-averaged viscosity distribution predicted by the shear-thinning non-Newtonian model. For St > or approximately= 100, the disparity between our results and those of a Newtonian fluid of constant viscosity grows with a decreasing ratio of the DC to AC components of the pressure-gradient amplitude below 50%. In particular, for any purely oscillatory pressure-gradient (vanishing DC component), the Womersley solution is a particularly poor predictor of the amplitude and phase of wall shear rate for over half of the flow cycle. Under such circumstances, the analytical models presented here provide a simple and accurate means of estimating instantaneous wall shear rate, knowing only the pressure gradient and hematocrit.

Blood Flow Velocity↗

[Hemodynamic analysis of pulsatile blood flow in arteries by MRI].

The purpose of this study was to analyze the hemodynamics of pulsatile blood flow in arteries by MRI. The blood flow velocity was calculated by dividing the traveled distance of blood bolus by the echo time obtained from DBI images. Pulsatile water flow in the phantom and blood flow in abdominal aorta of 27 volunteers were estimated by means of both the DBI image and an approximate equation of flow velocity. The measured flow well agreed with the actual flow in the flow phantom study. Three-dimensional flow velocity profiles calculated using the approximate equation were similar to the DBI images and had the characteristics of pulsatile flow. The negative flow velocity near the aortic wall could be expressed in the flow velocity profiles by the approximate equation. The maximum flow velocities at the center of the abdominal aorta and the time-averaged wall shear stress calculated by the approximate equation decreased with aging (r = -0.78 P < 0.0001 and r = -0.64 P < 0.0003, respectively). The present results suggest that the DBI method and analysis based on the approximate equation proposed here will be valuable to analyze the hemodynamics of pulsatile blood flow.

Adult↗