Steady flow velocity measurements in a pulmonary artery model with varying degrees of pulmonic stenosis

Velocity and flow visualization studies were conducted in an adult size pulmonary artery model with varying degrees of valvular stenosis, using a two dimensional laser Doppler anemometer system. Velocity measurements in the main, left and right branches of the pulmonary artery revealed that as the degree of pulmonic stenosis increased, the jet type flow created by the valve hit the distal wall of the LPA farther downstream from the junction of the bifurcation. This in turn led to higher levels of turbulent and disturbed flow, and larger secondary flow motion in the LPA compared to the RPA. The high levels of turbulence measured in the main and left pulmonary arteries with the stenotic valves, could lead to the clinically observed phenomenon of post stenotic dilatation in the MPA extending into the LPA.     

Secondary flow velocity patterns in a pulmonary artery model with varying degrees of valvular pulmonic stenosis: pulsatile in vitro studies

The objective of this study was to characterize in detail the secondary flow velocity patterns in an in vitro model of a human (adult) pulmonary artery with varying degrees of valvular pulmonic stenosis. A two-dimensional laser Doppler anemometer (LDA) system was used to map the flow fields in the main (MPA), left (LPA), and right (RPA) branches of the pulmonary artery model. The study was conducted in the Georgia Tech right heart pulse duplicator system. A pair of counter-rotating secondary flows were observed in each daughter branch in which the fluid moved outwardly along the side walls and then circled back inwardly toward the center of the vessel. For the case of the "normal" valve, the two counter-rotating secondary flows were symmetric about the centerline. The strength of secondary flows in the RPA was much stronger than in the LPA. However, as the pulmonic valve became more stenotic, the two counter-rotating secondary flows in both the LPA and RPA were no longer symmetric. In addition, the strength of secondary flows in both daughter branches increased with increasing degree of valvular stenosis. The increment in the LPA was, however, greater than in the RPA. The study demonstrates the importance of analyzing complex biological flows from a three-dimensional viewpoint.     

Axial flow velocity patterns in a pulmonary artery model with varying degrees of valvular pulmonic stenosis: pulsatile in vitro studies

With the advent of noninvasive clinical techniques which can measure blood flow velocities (Doppler ultrasound), it is suggested that a fundamental knowledge of the axial flow velocity patterns in the pulmonary artery, and the changes caused by stenosis, may be used to support accurate diagnosis of valvular pulmonic stenosis. The present study was designed to characterize the axial flow velocity patterns in an in vitro model of a human adult pulmonary artery with varying degrees of valvular pulmonic stenosis. A two-dimensional laser Doppler anemometer (LDA) system was used to map the flow fields in the main (MPA), left (LPA), and right (RPA) branches of the pulmonary artery model. The study was conducted in the Georgia Tech. right heart pulse duplicator system. It was observed that the axial flow velocity patterns in the MPA and the LPA change dramatically with increasing degree of valvular stenosis. This indicates that the axial flow velocity patterns in these two branches are strongly influenced by the degree of valvular stenosis. The axial flow velocity patterns in the RPA, however, do not change much with varying degrees of valvular stenosis, indicating that the axial flow fields in the RPA are mainly influenced by the geometry of the bifurcation. It may be concluded therefore, that the changes in the axial flow velocity patterns in the MPA and LPA (rather than in the RPA) could be sensitive and reliable indicators of the severity of the defect.     

Quantitative characterization of postnatal growth trends in proximal pulmonary arteries in rats by phase-contrast magnetic resonance imaging

Malformations of the pulmonary arteries can increase right heart workload and result in morbidity, heart failure, and death. With the increased use of murine models to study these malformations, there is a pressing need for an accurate and noninvasive experimental technique that is capable of characterizing pulmonary arterial hemodynamics in these animals. We describe the growth trends of pulmonary arteries in 13 male Sprague-Dawley rats at 20, 36, 52, 100, and 160 days of age with the introduction of phase-contrast MRI as such a technique. PCMRI results correlated closely with cardiac output measurements by ultrasound echocardiography and with fluorescent microspheres in right-left lung flow split (flow partition). Mean flow, average cross-sectional area, distensibility, and shear rates for the right and left pulmonary arteries (RPA and LPA) were calculated. The RPA was larger and received more flow at all times than the LPA (P < 0.0001). Right-left flow split did not change significantly with age, and arterial distensibility was not significantly different between RPA and LPA, except at 160 days (P < 0.01). Shear rates were much higher for the LPA than the RPA (P < 0.0001) throughout development. The RPA and LPA showed different structure-function relationships but obeyed similar allometric scaling laws, with scaling exponents comparable to those of the main pulmonary artery. This study is the first to quantitatively describe changes in RPA and LPA flows and sizes with development and to apply phase-contrast MRI techniques to pulmonary arteries in rats.     

Blood flow conditions in the proximal pulmonary arteries and vena cavae: healthy children during upright cycling exercise

Diagnostic testing in patients with congenital heart disease is usually performed supine and at rest, conditions not representative of their typical hemodynamics. Upright exercise measurements of blood flow may prove valuable in the assessment of these patients, but data in normal subjects are first required. With the use of a 0.5-T open magnet, a magnetic resonance-compatible exercise cycle, and cine phase-contrast techniques, time-dependent blood flow velocities were measured in the right (RPA), left (LPA), and main (MPA) pulmonary arteries and superior (SVC) and inferior (IVC) vena cavae of 10 healthy 10- to 14-yr-old subjects. Measurements were made at seated rest and during upright cycling exercise (150% resting heart rate). Mean blood flow (l/min) and reverse flow index were computed from the velocity data. With exercise, RPA and LPA mean flow increased 2.0 +/- 0.5 to 3.7 +/- 0.7 (P < 0.05) and 1.6 +/- 0.4 to 2.9 +/- 0.8 (P < 0.05), respectively. Pulmonary reverse flow index (rest vs. exercise) decreased with exercise as follows: MPA: 0.014 +/- 0.012 vs. 0.006 +/- 0.006 [P = not significant (NS)], RPA: 0.005 +/- 0.004 vs. 0.000 +/- 0.000 (P < 0.05), and LPA: 0.041 +/- 0.019 vs. 0.014 +/- 0.016 (P < 0.05). SVC and IVC flow increased from 1.5 +/- 0.2 to 1.9 +/- 0.6 (P = NS) and 1.6 +/- 0.4 to 4.9 +/- 1.3 (P < 0.05), respectively. A 56/44% RPA/LPA flow distribution at both rest and during exercise suggests blood flow distribution is dominated by distal pulmonary resistance. Reverse flow in the MPA appears to originate solely from the LPA while the RPA is in relative isolation. During seated rest, the SVC-to-IVC venous return ratio is 50/50%. With light/moderate cycling exercise, IVC flow increases by threefold, whereas SVC remains essentially constant.     

Hemodynamics of patient-specific aorta-pulmonary shunt configurations

Optimal hemodynamics in aorta-pulmonary shunt reconstruction is essential for improved post-operative recovery of the newborn congenital heart disease patient. However, prior to in vivo execution, the prediction of post-operative hemodynamics is extremely challenging due to the interplay of multiple confounding physiological factors. It is hypothesized that the post-operative performance of the surgical shunt can be predicted through computational blood flow simulations that consider patient size, shunt configuration, cardiac output and the complex three-dimensional disease anatomy. Utilizing only the routine patient-specific pre-surgery clinical data sets, we demonstrated an intelligent decision-making process for a real patient having pulmonary artery atresia and ventricular septal defect. For this patient, a total of 12 customized candidate shunt configurations are contemplated and reconstructed virtually using a sketch-based computer-aided anatomical editing tool. Candidate shunt configurations are evaluated based on the parameters that are computed from the flow simulations, which include 3D flow complexity, outlet flow splits, shunt patency, coronary perfusion and energy loss. Our results showed that the modified Blalock-Taussig (mBT) shunt has 12% higher right pulmonary artery (RPA) and 40% lower left pulmonary artery (LPA) flow compared to the central shunt configuration. Also, the RPA flow regime is distinct from the LPA, creating an uneven flow split at the pulmonary arteries. For all three shunt sizes, right mBT innominate and central configurations cause higher pulmonary artery (PA) flow and lower coronary artery pressure than right and left mBT subclavian configurations. While there is a trade-off between energy loss, flow split and coronary artery pressure, overall, the mBT shunts provide sufficient PA perfusion with higher coronary artery pressures and could be preferred for similar patients having PA overflow risk. Central shunts would be preferred otherwise particularly for cases with very low PA overflow risk.     

Angiogenic activation of valvular endothelial cells in aortic valve stenosis

Here, we demonstrate the angiogenic response of valvular endothelial cells to aortic valve (AV) stenosis using a new ex vivo model of aortic leaflets. Histological analysis revealed neovascularization within the cusps of stenotic but not of non-stenotic aortic valves. Correspondingly, the number of capillary-like outgrowth in 3D collagen gel was significantly higher in stenotic than in non-stenotic valves. Capillary-like sprouting was developed significantly faster in stenotic than in non-stenotic valves. New capillary sprouts from stenotic aortic valves exhibited the endothelial cell markers CD31, CD34 and von-Willebrand factor (vWF) as well as carcinoembryonic antigen cell adhesion molecule-1 (CEACAM1), Tie-2 and angiogenesis inhibitor endostatin. Western blot analyses revealed a significant increase of CEACAM1 and endostatin in stenotic aortic valve tissue. Electron microscopic examinations demonstrate that these capillary-like tubes are formed by endothelial cells containing Weibel-Palade bodies. Remarkably, inter-endothelial junctions are established and basement membrane material is partially deposited on the basal side of the endothelial tubes. Our data demonstrate the capillary-like sprout formation from aortic valves and suggest a role of angiogenesis in the pathogenesis of aortic valve stenosis. These data provide new insights into the mechanisms of valvular disorders and open new perspectives for prevention and early treatment of calcified aortic stenosis.     

Numerical investigation of regurgitation phenomena in pulmonary arteries of Tetralogy of Fallot patients after repair

Pulmonary regurgitation is a very common phenomenon in pulmonary arteries after repair of patients of Tetralogy of Fallot (TOF) which is the most common complex congenital heart diseases. The aim of this study is to use numerical approaches to simulate flow variations in pulmonary artery after repair of patients of TOF. We analyze the flow patterns in an in-vitro bifurcation pulmonary artery and consider effects of various regurgitation fractions (RF or b/f) in left pulmonary artery (LPA) and right pulmonary artery (RPA). We not only observe the variation of flow patterns, but also analyze the results of b/f and net volumetric flow rates in LPA and RPA. In general, the b/f of LPA is higher than RPA in the measured data provided by phase-contrast magnetic resonance imaging (PC-MRI). We validate the result using numerical approaches to analyze the flow patterns in pulmonary artery in this study. The results will be useful for medical doctors when they perform operations for TOF patients.     

Numerical simulation of steady turbulent flow through trileaflet aortic heart valves—II. Results on five models

Turbulent flow simulations are run for five aortic trileaflet valve geometries, ranging from a valve leaflet orifice area of 1.1 cm² (Model A1—very stenotic) to 5.0 cm² (Model A5—natural valve). The simulated data compares well with experimental measurements made downstream of various aortic trileaflet valves by Woo (PhD Thesis, 1984). The location and approximate width and length of recirculation regions are correctly predicted. The less stenotic valve models reattach at the end of the aortic sinus region, 1.1 diameters downstream of the valve. The central jet exiting the less stenotic valve models is not significantly different from fully developed flow, and therefore recovers very quickly downstream of the reattachment point. The more stenotic valves disturb the flow to a greater degree, generating recirculation regions large enough to escape the sinuses and reattach further downstream. Peak turbulent shear stress values downstream of the aortic valve models which approximated prosthetic valves are 125 and 300 N m⁻², very near experimental observations of 150 to 350 N m⁻². The predicted Reynolds stress profiles also present the correct shape, a double peak profile, with the location of the peak occuring at the location of maximum velocity gradient, which occurs near the recirculation region. The pressure drop across model A2 (leaflet orifice area 1.6 cm²) is 20 mmHg at 1.6 diameters downstream. This compares well with values ranging from 19.5 to 26.2 mmHg for valves of similar orifice areas. The pressure drop decreases with decreasing valve stenosis, to a negligible value across the least stenotic valve model. Based on the good agreement between experimental measurements of velocity, shear stress and pressure drop, compared to the simulated data, the model has the potential to be a valuable tool in the analysis of heart valve designs.     

In-vitro pulsatile flow visualization studies in a pulmonary artery model

In-vitro pulsatile flow visualization studies were conducted in an adult-sized pulmonary artery model to observe the effects of valvular pulmonic stenosis on the flow fields of the main, left and right pulmonary arteries. The flow patterns revealed that as the degree of stenosis increased, the jet-type flow created by the valve became narrower, and it impinged on the far (distal) wall of the left pulmonary artery further downstream from the junction of the bifurcation. This in turn led to larger regions of disturbed turbulent flow, as well as helical-type secondary flow motions in the left pulmonary artery, compared to the right pulmonary artery. The flow field in the main pulmonary artery also became more disturbed and turbulent, especially during peak systole and the deceleration phase. The flow visualization observations have been valuable in helping to conduct further quantitative studies such as pressure and velocity field mapping. Such studies are important to understanding the fluid mechanics characteristics of the main pulmonary artery and its two major branches.     

Effect of perivascular electromagnetic flow probes on pulmonary hemodynamics

We determined the effect of perivascular electromagnetic flow probes (EMF) on pulmonary hemodynamics in acute experiments. In seven dogs placement of the EMF on the main pulmonary artery (MPA) increased pulmonary arterial pulse pressure by 25% (17.8-21.9 cmH2O, P less than 0.005) and mean right ventricular pressure by 12% (23.2-25.9 cmH2O, P less than 0.001) but did not alter heart rate, systemic blood pressure, mean pulmonary arterial pressure, or right ventricular end-diastolic pressure. This response was not abolished by local application of lidocaine to the MPA. In three cats input impedance was calculated from measurements of pressure and flow in the MPA. Impedance was calculated with flow measured using an EMF and ultrasonic volume flow probe (USF), which avoids the constraining effect of the EMF. When flow was measured with an EMF rather than a USF, there was a significant difference in the impedance spectra (P less than 0.001), but it was only apparent in the moduli greater than six harmonics. We conclude that the EMF does affect right ventricular afterload in acute experiments and alters the measured input impedance.     

Bicuspid aortic valve aortopathies: An hemodynamics characterization in dilated aortas

Bicuspid aortic valve (BAV) aortopathy remains of difficult clinical management due to its heterogeneity and further assessment of related aortic hemodynamics is necessary. The aim of this study was to assess systolic hemodynamic indexes and wall stresses in patients with diverse BAV phenotypes and dilated ascending aortas. The aortic geometry was reconstructed from patient-specific images while the aortic valve was generated based on patient-specific measurements. Physiologic material properties and boundary conditions were applied and fully coupled fluid-structure interaction (FSI) analysis were conducted. Our dilated aortic models were characterized by the presence of abnormal hemodynamics with elevated degrees of flow skewness and eccentricity, regardless of BAV morphotype. Retrograde flow was also present. Both features, predicted by flow angle and flow reversal ratios, were consistently higher than those reported for non-dilated aortas. Right-handed helical flow was present, as well as elevated wall shear stress (WSS) on the outer ascending aortic wall. Our results suggest that the abnormal flow associated with BAV may play a role in aortic enlargement and progress it further on already dilated aortas.     

IB–LBM simulation of the haemocyte dynamics in a stenotic capillary

To study the behaviour of a haemocyte when crossing a stenotic capillary, the immersed boundary–lattice Boltzmann method was used to establish a quantitative analysis model. The haemocyte was assumed to be spherical and to have an elastic cell membrane, which can be driven by blood flow to adopt a highly deformable character. In the stenotic capillary, the spherical blood cell was stressed both by the flow and the wall dimension, and the cell shape was forced to be stretched to cross the stenosis. Our simulation investigated the haemocyte crossing process in detail. The velocity and pressure were anatomised to obtain information on how blood flows through a capillary and to estimate the degree of cell damage caused by excessive pressure. Quantitative velocity analysis results demonstrated that a large haemocyte crossing a small stenosis would have a noticeable effect on blood flow, while quantitative pressure distribution analysis results indicated that the crossing process would produce a special pressure distribution in the cell interior and to some extent a sudden change between the cell interior and the surrounding plasma.     

The effects of a glycerin-based blood analog on the testing of bioprosthetic heart valves

Detailed comparisons of aortic valvular flow using saline, with that using a glycerin-based blood analog in a pulse duplicator are reported. The experiments were carried out to determine whether exposure to glycerin caused stiffening of bioprosthetic valve leaflets. For two pericardial bioprostheses and for a mechanical valve we observed a fluid-dependent systolic volume flow, a fluid-dependent regurgitation volume, and fluid-dependent systolic pressure differences. Volume flow changes, both forward and reverse, are independent of valve type. The observed pressure differences, while proportional to fluid density for the mechanical valve, are fluid dependent in a more complicated way for the pericardial valves. However, no trend of changing valvular performance was observed over as much as 80 days of glycerin exposure, indicating that it is unlikely that the fluid-dependent performance was caused by glycerin absorption by the valve leaflets. We conclude that valid performance comparisons between mechanical and bioprosthetic valves may be made using a glycerin-based fluid. Furthermore, it appears that any detailed analysis of the physical mechanisms of valvular flow dissipation will require a properly matched blood analog.     

Experimental analysis of the influence of stenotic geometry on steady flow.

We studied the flow behavior under steady flow conditions in four models of cylindrical stenoses at Reynolds numbers from 150 to 920. The flow upstream of the constrictions was always fully developed. The constriction ratios of the rigid tubes (D) to the stenoses (d) were d/D = 0.273; 0.505; 0.548; 0.786. The pressure drop at various locations in the stenotic models was measured with water manometers. The flow was visualized with a photoelasticity apparatus using an aqueous birefringent solution. We also studied the flow behavior at pulsatile flow in a dog aorta with a constriction of 71%. The flow through stenotic geometries depends on the Reynolds number of the flow generated in the tube and the constriction ratio d/D. At low d/D ratios, (with the increased constriction), the flow separation zones (recirculation zones, so-called reattachment length) and flow disturbances increased with larger Reynolds numbers. At lower values, eddies were generated. At high Re, eddies were observed in the pre-stenotic regions. The pressure drop is a function of the length and internal diameter of the stenosis, respective ratio of stenosis to the main vessel and the Reynolds numbers. At low Re-numbers and low d/D, distinct recirculation zones were found close to the stenosis. The flow is laminar in the distal areas. Further experiments under steady and unsteady flow conditions in a dog aorta model with a constriction of 71% showed similar effects. High velocity fluctuations downstream of the stenosis were found in the dog aorta. A videotape demonstrates these results.     

The Role of Rubella in the Etiology of Supravalvular Aortic Stenosis

The possibility of an etiological relationship between rubella embryopathy and sporadic forms of supravalvular aortic stenosis is considered. A case is presented of a patient with rubella embryopathy and supravalvular aortic stenosis associated with pulmonary valvular and peripheral pulmonary artery stenosis, bicuspid aortic valve, aortic valve stenosis and subendothelial myocardial fibrosis. A review of the literature revealed many clinical and pathological features common to both syndromes. The hypothesis that rubella virus produced germ-cell mutation and subsequent persistence of rubella in the zygote produced further fetal damage is presented to explain these observations.     

Endothelin-A receptor blockade slows the progression of renal injury in experimental renovascular disease

Endothelin (ET)-1, a potent renal vasoconstrictor with mitogenic properties, is upregulated by ischemia and has been shown to induce renal injury via the ET-A receptor. The potential role of ET-A blockade in chronic renovascular disease (RVD) has not, to our knowledge, been previously reported. We hypothesized that chronic ET-A receptor blockade would preserve renal hemodynamics and slow the progression of injury of the stenotic kidney in experimental RVD. Renal artery stenosis, a major cause of chronic RVD, was induced in 14 pigs and observed for 6 wk. In half of the pigs, chronic ET-A blockade was initiated (RVD+ET-A, 0.75 mg·kg(-1)·day(-1)) at the onset of RVD. Single-kidney renal blood flow, glomerular filtration rate, and perfusion were quantified in vivo after 6 wk using multidetector computer tomography. Renal microvascular density was quantified ex vivo using three-dimensional microcomputer tomography, and growth factors, inflammation, apoptosis, and fibrosis were determined in renal tissue. The degree of stenosis and increase in blood pressure were similar in RVD and RVD+ET-A pigs. Renal hemodynamics, function, and microvascular density were decreased in the stenotic kidney but preserved by ET-A blockade, accompanied by increased renal expression of vascular endothelial growth factor, hepatocyte growth factor, and downstream mediators such as phosphorilated-Akt, angiopoietins, and endothelial nitric oxide synthase. ET-A blockade also reduced renal apoptosis, inflammation, and glomerulosclerosis. This study shows that ET-A blockade slows the progression of renal injury in experimental RVD and preserves renal hemodynamics, function, and microvascular density in the stenotic kidney. These results support a role for ET-1/ET-A as a potential therapeutic target in chronic RVD.