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.     

Insights from in-vitro flow visualization into the mechanism of systolic anterior motion of the mitral valve in hypertrophic cardiomyopathy under steady flow conditions.

Hypertrophic obstructive cardiomyopathy is a heart disease characterized by a thickened interventricular septum which narrows the left ventricular outflow tract, and by systolic anterior motion (SAM) of the mitral valve which can contact the septum and create dynamic subaortic obstruction. The most common explanation for SAM has been the Venturi mechanism which postulates that septal hypertrophy, by narrowing the outflow tract, produces high velocities and thus low pressure between the mitral valve and the septum, causing the valve leaflets to move anteriorly. This hypothesis, however, fails to explain why SAM often begins early in systole, when outflow tract velocities are low or negligible or why it may occur in the absence of septal hypertrophy. The goal of this study was therefore to investigate an alternative hypothesis in which structural abnormalities of the papillary muscles act as a primary cause of SAM by altering valve restraint and thereby changing the geometry of the closed mitral apparatus and its relationship to the surrounding flow field. In order to test this hypothesis, an in vitro model of the left ventricle which included an explanted human mitral valve with intact chords and papillary muscle apparatus was constructed. Flow visualization was used to observe the ventricular flow field and the mitral valve geometry. Displacing the papillary muscles anteriorly and closer to each other, as observed clinically in patients with cardiomyopathy and obstruction produced SAM in the absence of septal hypertrophy. Flow could be seen impacting on the upstream (posterior) surface of the leaflets; such flow is capable of producing form drag forces which can initiate and maintain SAM.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of hinge microflow fields of bileaflet mechanical heart valves implanted in different sinus shape and downstream geometry

The characterization of the bileaflet mechanical heart valves (BMHVs) hinge microflow fields is a crucial step in heart valve engineering. Earlier in vitro studies of BMHV hinge flow at the aorta position in idealized straight pipes have shown that the aortic sinus shapes and sizes may have a direct impact on hinge microflow fields. In this paper, we used a numerical study to look at how different aortic sinus shapes, the downstream aortic arch geometry, and the location of the hinge recess can influence the flow fields in the hinge regions. Two geometric models for sinus were investigated: a simplified axisymmetric sinus and an idealized three-sinus aortic root model, with two different downstream geometries: a straight pipe and a simplified curved aortic arch. The flow fields of a 29-mm St Jude Medical BMHV with its four hinges were investigated. The simulations were performed throughout the entire cardiac cycle. At peak systole, recirculating flows were observed in curved downsteam aortic arch unlike in straight downstream pipe. Highly complex three-dimensional leakage flow through the hinge gap was observed in the simulation results during early diastole with the highest velocity at 4.7 m/s, whose intensity decreased toward late diastole. Also, elevated wall shear stresses were observed in the ventricular regions of the hinge recess with the highest recorded at 1.65 kPa. Different flow patterns were observed between the hinge regions in straight pipe and curved aortic arch models. We compared the four hinge regions at peak systole in an aortic arch downstream model and found that each individual hinge did not vary much in terms of the leakage flow rate through the valves.     

An analysis of turbulent shear stresses in leakage flow through a bileaflet mechanical prostheses

In this work, estimates of turbulence were made from pulsatile flow laser Doppler velocimetry measurements using traditional phase averaging and averaging after the removal of cyclic variation. These estimates were compared with estimates obtained from steady leakage flow LDV measurements and an analytical method. The results of these studies indicate that leakage jets which are free and planar in shape may be more unstable than other leakage jets, and that cyclic variation does not cause a gross overestimation of the Reynolds stresses at large distances from the leakage jet orifice.     

Mechanism of incomplete mitral leaflet coaptation--interaction of chordal restraint and changes in mitral leaflet coaptation geometry. Insight from in vitro validation of the premise of force equilibrium

Clinically observed incomplete mitral leaflet coaptation was reproduced in vitro by altering the balance of the chordal tethering and chordal coapting force components. Mitral leaflet coaptation geometry was distorted by changes of the spatial relations between the papillary muscles and the mitral valve as well as hemodynamics. Mitral leaflet malalignment was accentuated by a redistribution of the chordal tethering and coapting force components. For the overall assessment of systolic mitral leaflet configuration in functional mitral regurgitation it is important to consider the interaction between chordal restraint and an altered mitral leaflet coaptation geometry.     

Mechanistic studies of catechol generation from secondary quinone amines relevant to indole formation and tyrosinase activation

The biological significance of the spontaneous cyclization and redox reactions of ortho-quinone amines is that these appear to be the mechanism of formation of the indolic components of melanin and are also involved in the autoactivation of tyrosinase. We have previously shown that activation of tyrosinase is prevented by the formation of a cyclic betaine from a tertiary amine analogue. Evidence is presented to show that cyclization of ortho-quinones by Michael addition also occurs in the oxidation of secondary catecholamines. Three varieties of cyclic product have been detected and their formation is influenced by the nature of the N-substituent. Five-membered betaine rings form directly and, although six- and seven-membered rings also form, a transient spiro isomer of the ortho-quinone was in some cases detected as an intermediate. The heterocyclic products formed as betaines undergo redox exchange with residual quinone to form the corresponding aminochromes. We have established the kinetic constants of these reactions, either directly by pulse radiolysis measurements or by inference using a computer model of the reaction pathway to fit the observed data. To investigate the potential biological applications of this chemistry the system was also examined by tyrosinase-catalysed oxidation of the catecholamine substrates in which there is re-oxidation of the catechol formed by the redox exchange reaction and enables measurement of oxygen utilization stoichiometry. We show that the redox exchange reaction is unaffected by side-chain modification whereas cyclization is dependent on both electronic and steric factors. In the light of these studies we conclude that the failure of tertiary amine-derived betaines to undergo redox exchange, and thus block in vitro activation of tyrosinase, is due to the absence of a second exchangeable proton.     

The congenital bicuspid aortic valve can experience high-frequency unsteady shear stresses on its leaflet surface

The bicuspid aortic valve (BAV) is a common congenital malformation of the aortic valve (AV) affecting 1% to 2% of the population. The BAV is predisposed to early degenerative calcification of valve leaflets, and BAV patients constitute 50% of AV stenosis patients. Although evidence shows that genetic defects can play a role in calcification of the BAV leaflets, we hypothesize that drastic changes in the mechanical environment of the BAV elicit pathological responses from the valve and might be concurrently responsible for early calcification. An in vitro model of the BAV was constructed by surgically manipulating a native trileaflet porcine AV. The BAV valve model and a trileaflet AV (TAV) model were tested in an in vitro pulsatile flow loop mimicking physiological hemodynamics. Laser Doppler velocimetry was used to make measurements of fluid shear stresses on the leaflet of the valve models using previously established methodologies. Furthermore, particle image velocimetry was used to visualize the flow fields downstream of the valves and in the sinuses. In the BAV model, flow near the leaflets and fluid shear stresses on the leaflets were much more unsteady than for the TAV model, most likely due to the moderate stenosis in the BAV and the skewed forward flow jet that collided with the aorta wall. This additional unsteadiness occurred during mid- to late-systole and was composed of cycle-to-cycle magnitude variability as well as high-frequency fluctuations about the mean shear stress. It has been demonstrated that the BAV geometry can lead to unsteady shear stresses under physiological flow and pressure conditions. Such altered shear stresses could play a role in accelerated calcification in BAVs.     

In vitro hemodynamic investigation of the embryonic aortic arch at late gestation

This study focuses on the dynamic flow through the fetal aortic arch driven by the concurrent action of right and left ventricles. We created a parametric pulsatile computational fluid dynamics (CFD) model of the fetal aortic junction with physiologic vessel geometries. To gain a better biophysical understanding, an in vitro experimental fetal flow loop for flow visualization was constructed for identical CFD conditions. CFD and in vitro experimental results were comparable. Swirling flow during the acceleration phase of the cardiac cycle and unidirectional flow following mid-deceleration phase were observed in pulmonary arteries (PA), head-neck vessels, and descending aorta. Right-to-left (oxygenated) blood flowed through the ductus arteriosus (DA) posterior relative to the antegrade left ventricular outflow tract (LVOT) stream and resembled jet flow. LVOT and right ventricular outflow tract flow mixing had not completed until approximately 3.5 descending aorta diameters downstream of the DA insertion into the aortic arch. Normal arch model flow patterns were then compared to flow patterns of four common congenital heart malformations that include aortic arch anomalies. Weak oscillatory reversing flow through the DA junction was observed only for the Tetralogy of Fallot configuration. PA and hypoplastic left heart syndrome configurations demonstrated complex, abnormal flow patterns in the PAs and head-neck vessels. Aortic coarctation resulted in large-scale recirculating flow in the aortic arch proximal to the DA. Intravascular flow patterns spatially correlated with abnormal vascular structures consistent with the paradigm that abnormal intravascular flow patterns associated with congenital heart disease influence vascular growth and function.     

Design of an ex vivo culture system to investigate the effects of shear stress on cardiovascular tissue

Mechanical forces are known to affect the biomechanical properties of native and engineered cardiovascular tissue. In particular, shear stress that results from the relative motion of heart valve leaflets with respect to the blood flow is one important component of their mechanical environment in vivo. Although different types of bioreactors have been designed to subject cells to shear stress, devices to expose biological tissue are few. In an effort to address this issue, the aim of this study was to design an ex vivo tissue culture system to characterize the biological response of heart valve leaflets subjected to a well-defined steady or time-varying shear stress environment. The novel apparatus was designed based on a cone-and-plate viscometer. The device characteristics were defined to limit the secondary flow effects inherent to this particular geometry. The determination of the operating conditions producing the desired shear stress profile was streamlined using a computational fluid dynamic (CFD) model validated with laser Doppler velocimetry. The novel ex vivo tissue culture system was validated in terms of its capability to reproduce a desired cone rotation and to maintain sterile conditions. The CFD results demonstrated that a cone angle of 0.5 deg, a cone radius of 40 mm, and a gap of 0.2 mm between the cone apex and the plate could limit radial secondary flow effects. The novel cone-and-plate permits to expose nine tissue specimens to an identical shear stress waveform. The whole setup is capable of accommodating four cone-and-plate systems, thus concomitantly subjecting 36 tissue samples to desired shear stress condition. The innovative design enables the tissue specimens to be flush mounted in the plate in order to limit flow perturbations caused by the tissue thickness. The device is capable of producing shear stress rates of up to 650 dyn cm(-2) s(-1) (i.e., maximum shear stress rate experienced by the ventricular surface of an aortic valve leaflet) and was shown to maintain tissue under sterile conditions for 120 h. The novel ex vivo tissue culture system constitutes a valuable tool toward elucidating heart valve mechanobiology. Ultimately, this knowledge will permit the production of functional tissue engineered heart valves, and a better understanding of heart valve biology and disease progression.