A detailed fluid mechanics study of tilting disk mechanical heart valve closure and the implications to blood damage

Hemolysis and thrombosis are among the most detrimental effects associated with mechanical heart valves. The strength and structure of the flows generated by the closure of mechanical heart valves can be correlated with the extent of blood damage. In this in vitro study, a tilting disk mechanical heart valve has been modified to measure the flow created within the valve housing during the closing phase. This is the first study to focus on the region just upstream of the mitral valve occluder during this part of the cardiac cycle, where cavitation is known to occur and blood damage is most severe. Closure of the tilting disk valve was studied in a "single shot" chamber driven by a pneumatic pump. Laser Doppler velocimetry was used to measure all three velocity components over a 30 ms period encompassing the initial valve impact and rebound. An acrylic window placed in the housing enabled us to make flow measurements as close as 200 microm away from the closed occluder. Velocity profiles reveal the development of an atrial vortex on the major orifice side of the valve shed off the tip of the leaflet. The vortex strength makes this region susceptible to cavitation. Mean and maximum axial velocities as high as 7 ms and 20 ms were recorded, respectively. At closure, peak wall shear rates of 80,000 s(-1) were calculated close to the valve tip. The region of the flow examined here has been identified as a likely location of hemolysis and thrombosis in tilting disk valves. The results of this first comprehensive study measuring the flow within the housing of a tilting disk valve may be helpful in minimizing the extent of blood damage through the combined efforts of experimental and computational fluid dynamics to improve mechanical heart valve designs.     

Comparative in vitro study of bileaflet and tilting disk valve behavior in the pulmonary position

A study of mechanical heart valve behavior in the pulmonary position as a function of pulmonary vascular resistance is reported for the St. Jude Medical bileaflet (SJMB) valve and the MedicalCV Omnicarbon (OTD) tilting disk valve. Tests were conducted in a pulmonic mock circulatory system and impedance was varied in terms of system pulmonary vascular resistance (PVR). An impedance spectrum was found using instantaneous pulmonary artery pressure and flow rate curves. Both valves fully opened and closed at and above a nominal PVR of 3.0 mmHg/L/min. The SJMB valve was prone to leaflet bounce at closure, but otherwise completely closed, at settings above and below this nominal setting. At PVR values at and below 2.0 mmHg/L/min, the SJMB valve exhibited two types of leaflet aberrant behavior: single leaflet only closure while the other leaflet fluttered, and incomplete closure where both leaflets flutter but neither remain fully closed. The OTD valve fully opened and closed to a PVR value of 1.6 mmHg/L/min. At lower values, the valve did not close. Valves designed for the left heart can show aberrant behavior under normal conditions as pulmonary valves.     

The first heart sound during the isovolumetric contraction

We make the first attempt to construct a qualitative theory covering the whole process of the major part of the first heart sound from an electrical activation to the phonocardiographic observations at the thorax. We calculate the amplitudes and frequencies of the radiated pressures during the isovolumetric contraction period generated by the muscular wall of the left ventricle and by the valves considered as a spherical shell and two-dimensional membranes, respectively. The analysis shows that both the hemodynamic and the valvular theory are able to explain most of the characteristic features of the first heart sound (linear relation between the amplitudes of the radiated pressure and the slope of the left ventricular pressure-time curve; directional polarity of the amplitudes; equidistant frequency peaks with a decline in amplitudes). However, existing magnitudes of the set of physiological parameters involved seems to favour the hemodynamic theory of the first heart sound. The aortic valve can be neglected as a source of sound. The initial conditions (like valve closure velocity), according to our theory, cannot be important. The predicted time-plot and frequency spectrum of the radiated pressure show a general resemblance with the recorded ones. It is essential to have considerably more quantitative acoustic data both for normal and diseased hearts for subsequent theoretical development.     

Cavitation phenomena in mechanical heart valves: the role of squeeze flow velocity and contact area on cavitation initiation between two impinging rods

In this study, the closing dynamics of two impinging rods were experimentally analyzed to simulate the cavitation phenomena associated with mechanical heart valve closure. The purpose of this study was to investigate the cavitation phenomena with respect to squeeze flow between two impinging surfaces and the parameter that influences cavitation inception. High-speed flow imaging was employed to visualize and identify regions of cavitation. The images obtained favored squeeze flow as an important mechanism in cavitation inception. A correlation study of the effects of impact velocities, contact areas and squeeze flow velocity on cavitation inception showed that increasing impact velocities results in an increase in the risk of cavitation. It was also shown that for similar impact velocities, regions near the point of impact were found to cavitate later for those with smaller contact areas. It was found that the decrease in contact areas and squeeze flow velocities would delay the onset and reduce the intensity of cavitation. It is also interesting to note that the squeeze flow velocity alone does not provide an indication if cavitation inception will occur. This is corroborated by the wide range of published critical squeeze flow velocity required for cavitation inception. It should be noted that the temporal acceleration of fluid, often neglected in the literature, can also play an important role on cavitation inception for unsteady flow phenomenon. This is especially true in mechanical heart valves, where for the same leaflet closing velocity, valves with a seat stop were observed to cavitate earlier. Based on these results, important inferences may be made to the design of mechanical heart valves with regards to cavitation inception.     

Influence of stent height upon stresses on the cusps of closed bioprosthetic valves

A finite element model of a bioprosthetic heart valve was developed to determine the influence of the stent height on leaflet stresses under various pressure loading conditions after valve closure. A nonlinear solution was used to obtain the stresses in the leaflets for stent heights of 14.6 mm, 19.0 mm and 22.0 mm respectively. The basic assumptions included an elliptic-paraboloid for a relaxed leaflet shape, a rigid stent, isotropic leaflet material property with a Poisson's ratio of 0.45, a uniform leaflet thickness and a stress dependent Young's modulus. The model predicted an increase of stresses on the closed leaflets as the stent height was reduced. This observation appears to mitigate, to some extent, the hemodynamic benefits thought to accompany the reduction of stent height of bioprosthetic valves.     

Medusoid release and spawning of Macrorynchia philippina Kirchenpauer, 1872 (Cnidaria,Hydrozoa,Aglaopheniidae)

The life cycle of the aglaopheniid Macrorynchia philippina Kirchenpauer, 1872, is re-described from examination of live specimens collected from Réunion Island, Indian Ocean. Fertile colonies were collected on the outer slope of the coral reef and medusoid release happened a few hours later. Video sequences were recorded. Colonies were hermaphroditic: each phylactocarp contained one female and one male gonotheca. Sexual dimorphism was remarkable: sex could be recognized by colour, the female being red ochre, including about 40 oocytes disposed in a mosaic feature, and the male yellow ochre, having a homogeneous mass of spermatozoa. The blastostyle ran all around the gonangium near the closure of the two valves of the gonotheca, forming gubernacula. A ring of refringent corpuscles was clearly visible near the apex. Medusoids were indistinguishable inside the gonotheca. Male and female medusoids were released simultaneously at gamete maturity. Medusoid release involved the basal rupture of the blastostyle and the rupture of the links between the ectoderm surrounded the medusoid (the mantle), including the blastostyle (the mantle), and the gonothecal perisarc. While the two valves of the gonotheca were pushed and drew aside, the medusoid emerged by slipping out of the mantle that ruptured distally, forming a sheath; the bell of the medusoid did not contract. Immediately after emergence, quick and strong contractions of the bell allowed the medusoid to swim and induced spawning by breaking the ectoderm surrounding the gametic mass around the spadix. Spawning lasted only a few minutes: both oocytes and spermatozoa were expelled at each contraction. Spent medusoids remained alive only about 2 h. External fertilization gave rise to planulae 1 day later.     

Biomechanical properties of native and tissue engineered heart valve constructs

Due to the increasing number of heart valve diseases, there is an urgent clinical need for off-the-shelf tissue engineered heart valves. While significant progress has been made toward improving the design and performance of both mechanical and tissue engineered heart valves (TEHVs), a human implantable, functional, and viable TEHV has remained elusive. In animal studies so far, the implanted TEHVs have failed to survive more than a few months after transplantation due to insufficient mechanical properties. Therefore, the success of future heart valve tissue engineering approaches depends on the ability of the TEHV to mimic and maintain the functional and mechanical properties of the native heart valves. However, aside from some tensile quasistatic data and flexural or bending properties, detailed mechanical properties such as dynamic fatigue, creep behavior, and viscoelastic properties of heart valves are still poorly understood. The need for better understanding and more detailed characterization of mechanical properties of tissue engineered, as well as native heart valve constructs is thus evident. In the current review we aim to present an overview of the current understanding of the mechanical properties of human and common animal model heart valves. The relevant data on both native and tissue engineered heart valve constructs have been compiled and analyzed to help in defining the target ranges for mechanical properties of TEHV constructs, particularly for the aortic and the pulmonary valves. We conclude with a summary of perspectives on the future work on better understanding of the mechanical properties of TEHV constructs.     

Lumped parameter model for computing the minimum pressure during mechanical heart valve closure

The cavitation inception threshold of mechanical heart valves has been shown to be highly variable. This is in part due to the random distribution of the initial and final conditions that characterize leaflet closure. While numerous hypotheses exist explaining the mechanisms of inception, no consistent scaling laws have been developed to describe this phenomenon due to the complex nature of these dynamic conditions. Thus in order to isolate and assess the impact of these varied conditions and mechanisms on inception, a system of ordinary differential equations is developed to describe each system component and solved numerically to predict the minimum pressure generated during valve closure. In addition, an experiment was conducted in a mock circulatory loop using an optically transparent size 29 bileaflet valve over a range of conditions to calibrate and validate this model under physiological conditions. High-speed video and high-response pressure measurements were obtained simultaneously to characterize the relationship between the valve motion, fluid motion, and negative pressure transients during closure. The simulation model was calibrated using data from a single closure cycle and then compared to other experimental flow conditions and to results found in the literature. The simulation showed good agreement with the closing dynamics and with the minimum pressure trends in the current experiment. Additionally, the simulation suggests that the variability observed experimentally (when using dP/dt alone as the primary measure of cavitation inception) is predictable. Overall, results from the current form of this lumped parameter model indicate that it is a good engineering assessment tool.     

Age and individual variability of aortic valve structure in man

In persons of both sex at the age beginning from birth up to 90 years. 275 aortal valves have been investigated. A morphological classification of the valves has been suggested depending on peculiarities of their structure and main dimentions: valves with the valvula surfaces looking as a part of a spheroid, ellipsoid, or having a stepwise, cochliowise form; according to the mode of the valvula closure when the valve is closed: with straight, arched and wavy lines of closure; according to the size: valves with predominant dimentions of one valvula when two others are equal, valves with two equal valvulae and both are larger than the third one, valves with equal valvulae, valves with three different valvulae. Distribution of various types of the valves in accordance with the given classification is determined, the most frequently occurring forms are demonstrated. The valvulae grow in different directions unevenly and asynchronously with the aortal ostium growth, therefore during certain age periods a probability on a nonhermetic valve increases, especially from 1 up to 3 and from 56 up to 70 years of age.     

Dynamic modelling of prosthetic chorded mitral valves using the immersed boundary method

Current artificial heart valves either have limited lifespan or require the recipient to be on permanent anticoagulation therapy. In this paper, effort is made to assess a newly developed bileaflet valve prosthesis made of synthetic flexible leaflet materials, whose geometry and material properties are based on those of the native mitral valve, with a view to providing superior options for mitral valve replacement. Computational analysis is employed to evaluate the geometric and material design of the valve, by investigation of its mechanical behaviour and unsteady flow characteristics. The immersed boundary (IB) method is used for the dynamic modelling of the large deformation of the valve leaflets and the fluid-structure interactions. The IB simulation is first validated for the aortic prosthesis subjected to a hydrostatic loading. The predicted displacement fields by IB are compared with those obtained using ANSYS, as well as with experimental measurements. Good quantitative agreement is obtained. Moreover, known failure regions of aortic prostheses are identified. The dynamic behaviour of the valve designs is then simulated under four physiological pulsatile flows. Experimental pressure gradients for opening and closure of the valves are in good agreement with IB predictions for all flow rates for both aortic and mitral designs. Importantly, the simulations predicted improved physiological haemodynamics for the novel mitral design. Limitation of the current IB model is also discussed. We conclude that the IB model can be developed to be an extremely effective dynamic simulation tool to aid prosthesis design.     

Wavelet transforms in the analysis of mechanical heart valve cavitation

Cavitation is known to cause blood element damage and may introduce gaseous emboli into the cerebral circulation, increasing the patient's risk of stroke. Discovering methods to reduce the intensity of cavitation induced by mechanical heart valves (MHVs) has long been an area of interest. A novel approach for analyzing MHV cavitation is presented. A wavelet denoising method is explored because currently used analytical techniques fail to suitably unmask the cavitation signal from other valve closing sounds and noise detected with a hydrophone. Wavelet functions are used to denoise the cavitation signal during MHV closure and rebound. The wavelet technique is applied to the signal produced by closure of a 29-mm Medtronic-Hall MHV in degassed water with a gas content of 5 ppm. Valve closing dynamics are investigated under loading conditions of 500, 2500, and 4500 mm Hg/s. The results display a marked improvement in the quantity and quality of information that can be extracted from acoustic cavitation signals using the wavelet technique compared to conventional analytical techniques. Time and frequency data indicate the likelihood and characteristics of cavitation formation under specified conditions. Using this wavelet technique we observe an improved signal-to-noise ratio, an enhanced time-dependent aspect, and the potential to minimize valve closing sounds, which disguise individual cavitation events. The overall goal of this work is to eventually link specific valves with characteristic waveforms or distinct types of cavitation, thus promoting improved valve designs.     

Comparison of first and second heart sounds after mechanical heart valve replacement

In this article, the spectral features of first heart sounds (S1) and second heart sounds (S2), which comprise the mechanical heart valve sounds obtained after aortic valve replacement (AVR) and mitral valve replacement (MVR), are compared to find out the effect of mechanical heart valve replacement and recording area on S1 and S2. For this aim, the Welch method and the autoregressive (AR) method are applied on the S1 and S2 taken from 66 recordings of 8 patients with AVR and 98 recordings from 11 patients with MVR, thereby yielding power spectrum of the heart sounds. Three features relating to frequency of heart sounds and three features relating to energy of heart sounds are obtained. Results show that in comparison to natural heart valves, mechanical heart valves contain higher frequency components and energy, and energy and frequency components do not show common behaviour for either AVR or MVR depending on the recording areas. Aside from the frequency content and energy of the sound generated by mechanical heart valves being affected by the structure of the lungs–thorax and the recording areas, the pressure across the valve incurred during AVR or MVR is a significant factor in determining the frequency and energy levels of the valve sound produced. Though studies on native heart sounds as a non-invasive diagnostic method has been done for many years, it is observed that studies on mechanical heart valves sounds are limited. The results of this paper will contribute to other studies on using a non-invasive method for assessing the mechanical heart valve sounds.     

Enhanced accumulation of the isoprostane, 8-epi-PGF2 alpha,in human aortic and pulmonary valves of patients with coronary heart disease

The aim of the present study was to investigate whether the isoprostane 8-epi-PGF2 alpha differently accumulates in semilunar valves of patients suffering from coronary heart disease (CHD, n = 19) as compared to valves from healthy heart donors (controls, n = 6). Sections from isolated aortic and pulmonary valves were analyzed by semiquantitative immunohistochemistry. The 8-epi-PGF2 alpha-content was determined by using a specific radioimmunoassay. The accumulation of 8-epi-PGF2 alpha in both valves was higher in CHD-patients in comparison to controls (Aortic valves: 36.49 +/- 11.26% vs. 15.78 +/- 3.04%; pulmonary valves: 46.79 +/- 9.80% vs. 14.99 +/- 3.57%). The results from the radioimmunoassay revealed comparable findings in both groups (CHD vs. controls: 395.95 +/- 86.09 vs. 139.50 +/- 47.46 pg/mg protein in the aortic valves and 430.47 +/- 76.30 vs. 147.33 +/- 53.84 pg/mg protein in pulmonary valves). Pulmonary valves seem to be more susceptible to oxidative stress than aortic valves as evidenced by a higher accumulation of 8-epi-PGF2 alpha in CHD patients. Considering the data presented in this study, we suggest that 8-epi-PGF2 alpha is a valuable indicator of oxidative injury in human semilunar valves.     

Arylamine N-acetyltransferase 2 expression in the developing heart.

Murine arylamine N-acetyltransferase 2 (NAT2) is expressed in the developing heart and in the neural tube at the time of closure. Classically described as a xenobiotic metabolizing enzyme, there is increasing evidence for a distinct biological role for murine NAT2. We have characterized the expression of arylamine N-acetyltransferase 2 during cardiogenesis, mapping its expression in vivo, using a lacZ insertion deletion, and also in vitro, by measuring NAT2 enzyme activity. These findings show that cardiac Nat2 expression is both temporally and spatially regulated during development. In neonatal mice, cardiac Nat2 expression is most extensive in the central fibrous body and is evident in the atrioventricular valves and the valves of the great vessels. Whereas Nat2 expression is not detected in ventricular myocardial cells, Nat2 is strongly expressed in scattered cells in the region of the sinus node, the epicardium of the right atrial appendage, and in the pulmonary artery. Expression of active NAT2 protein is maximal when the developing heart attains the adult circulation pattern and moves from metabolizing glucose to fatty acids. NAT2 acetylating activity in cardiac tissue from Nat2(-/-) and Nat2(+/-) mice indicates a lack of compensating acetylating activity either from other acetylating enzymes or by NAT2 encoded by the wild-type Nat2 allele in Nat2(+/-) heterozygotes. The temporal and spatial control of murine Nat2 expression points to an endogenous role distinct from xenobiotic metabolism and indicates that Nat2 expression may be useful as a marker in cardiac development.     

Development of a model of a multi-lymphangion lymphatic vessel incorporating realistic and measured parameter values

Our published model of a lymphatic vessel consisting of multiple actively contracting segments between non-return valves has been further developed by the incorporation of properties derived from observations and measurements of rat mesenteric vessels. These included (1) a refractory period between contractions, (2) a highly nonlinear form for the passive part of the pressure–diameter relationship, (3) hysteretic and transmural-pressure-dependent valve opening and closing pressure thresholds and (4) dependence of active tension on muscle length as reflected in local diameter. Experimentally, lymphatic valves are known to be biased to stay open. In consequence, in the improved model, vessel pumping of fluid suffers losses by regurgitation, and valve closure is dependent on backflow first causing an adverse valve pressure drop sufficient to reach the closure threshold. The assumed resistance of an open valve therefore becomes a critical parameter, and experiments to measure this quantity are reported here. However, incorporating this parameter value, along with other parameter values based on existing measurements, led to ineffective pumping. It is argued that the published measurements of valve-closing pressure threshold overestimate this quantity owing to neglect of micro-pipette resistance. An estimate is made of the extent of the possible resulting error. Correcting by this amount, the pumping performance is improved, but still very inefficient unless the open-valve resistance is also increased beyond the measured level. Arguments are given as to why this is justified, and other areas where experimental data are lacking are identified. The model is capable of future adaptation as new experimental data appear.     

A note on the blood analog for in-vitro testing of heart valve bioprostheses

Glycerol solution with the viscosity coefficient similar to that of blood is used in evaluating the performance characteristics of prosthetic heart valves in the laboratory. However, physiological saline solution is used as a test fluid in testing tissue heart valves even though the viscosity coefficient does not match that of human blood. It is commonly believed that glycerol is absorbed by the tissue valves and hence the leaflets become stiff, making the test results invalid. However, in our laboratory a comparison of tissue valves exposed to glycerine solution at various times does not indicate any difference in the leaflet opening characteristics. Hence, it is suggested that glycerine solution be used as a test fluid for the evaluation of tissue valves also.     

Protocols for thawing and cryoprotectant dilution of heart valves

PURPOSE: To reduce the time taken for thawing and removal of cryoprotectant from heart valves. METHODS: Three sets of experiments were carried out using porcine heart valves. The valves in all three experiments were first exposed to 10% (v/v) dimethyl sulphoxide (DMSO) by a 2-step protocol. Outcome was determined after the various experimental treatments by monitoring the outgrowth of cells from valve leaflet explants. Experiment 1-Dilution protocol. Valves exposed to 10% DMSO were subjected to 4-, 2- or 1-step dilution to remove the DMSO. Experiment 2-Warming rate. The rate of warming was increased by reducing the volume of cryoprotectant medium in which the valves were frozen. Valves were exposed to 10% DMSO, frozen in different volumes (100, 50, 25 or 0 ml) of cryoprotectant medium, and warmed in a 37 degrees C water bath. The DMSO was removed by 4-step dilution. Experiment 3-Standard vs. Modified protocol. Valves were either frozen in 100 ml 10% DMSO, thawed, and subjected to 4-step dilution (Standard) or frozen in 50 ml 10% DMSO, thawed, and the DMSO removed by single-step dilution (Modified). RESULTS: Neither the rate of warming nor the rate of dilution of DMSO had any influence on the subsequent outgrowth of valve leaflet fibroblasts. There were no differences in the outgrowth of cells from valve leaflets cryopreserved by the Standard or Modified protocols. CONCLUSION: The time taken for thawing and dilution of heart valves could be reduced from >20 min to <10 min without detriment to the viability of the leaflet fibroblasts. This should have a positive impact on valve replacement surgery as the thawing and dilution of valves are typically carried out while the patients are on cardiopulmonary bypass.