Protocol for Relative Hydrodynamic Assessment of Tri-leaflet Polymer Valves

Limitations of currently available prosthetic valves, xenografts, and homografts have prompted a recent resurgence of developments in the area of tri-leaflet polymer valve prostheses. However, identification of a protocol for initial assessment of polymer valve hydrodynamic functionality is paramount during the early stages of the design process. Traditional in vitro pulse duplicator systems are not configured to accommodate flexible tri-leaflet materials; in addition, assessment of polymer valve functionality needs to be made in a relative context to native and prosthetic heart valves under identical test conditions so that variability in measurements from different instruments can be avoided. Accordingly, we conducted hydrodynamic assessment of i) native (n = 4, mean diameter, D = 20 mm), ii) bi-leaflet mechanical (n= 2, D = 23 mm) and iii) polymer valves (n = 5, D = 22 mm) via the use of a commercially available pulse duplicator system (ViVitro Labs Inc, Victoria, BC) that was modified to accommodate tri-leaflet valve geometries. Tri-leaflet silicone valves developed at the University of Florida comprised the polymer valve group. A mixture in the ratio of 35:65 glycerin to water was used to mimic blood physical properties. Instantaneous flow rate was measured at the interface of the left ventricle and aortic units while pressure was recorded at the ventricular and aortic positions. Bi-leaflet and native valve data from the literature was used to validate flow and pressure readings. The following hydrodynamic metrics were reported: forward flow pressure drop, aortic root mean square forward flow rate, aortic closing, leakage and regurgitant volume, transaortic closing, leakage, and total energy losses. Representative results indicated that hydrodynamic metrics from the three valve groups could be successfully obtained by incorporating a custom-built assembly into a commercially available pulse duplicator system and subsequently, objectively compared to provide insights on functional aspects of polymer valve design.     

An apparatus for altering the mechanical load of the respiratory system

We describe an apparatus for altering the mechanical load against which the respiratory muscles operate in humans. A closed system incorporates a rolling seal spirometer. The spirometer piston shaft is coupled to a fast-responding linear actuator that develops force in proportion to desired command signals. The command signal may be flow (resistive loading or unloading), volume (elastic loading or unloading), constant voltage (continuous positive or negative pressure), or any external function. Combinations of loads can be applied. Logic circuits permit application of the load at specific times during the respiratory cycle, and the magnitude of the loads is continuously adjustable. Maximum pressure output is +/- 20 cmH2O. The apparatus permits loading or unloading over a range of ventilation extending from resting levels to those observed during high levels of exercise (over 100 l/min). In response to a square-wave input, pressure rises exponentially with a time constant of 20 ms.     

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.     

Vortex shedding as a mechanism for free emboli formation in mechanical heart valves

The high incidence of thromboembolic complications of mechanical heart valves (MHV) limits their success as permanent implants. The thrombogenicity of all MHV is primarily due to platelet activation by contact with foreign surfaces and by nonphysiological flow patterns. The latter include elevated flow stresses and regions of recirculation of blood that are induced by valve design characteristics. A numerical simulation of unsteady turbulent flow through a bileaflet MHV was conducted, using the Wilcox k-omega turbulence model for internal low-Reynolds-number flows, and compared to quantitative flow visualization performed in a pulse duplicator system using Digital Particle Image Velocimetry (DPIV). The wake of the valve leaflet during the deceleration phase revealed an intricate pattern of interacting shed vortices. Particle paths showed that platelets that were exposed to the highest flow stresses around the leaflets were entrapped within the shed vortices. Potentially activated, such platelets may tend to aggregate and form free emboli. Once formed, such free emboli would be convected downstream by the shed vortices, increasing the risk of systemic emboli.     

Effect of systolic flow rate on the prediction of effective prosthetic valve orifice area

The Gorlin equation for the hemodynamic assessment of valve area is commonly used in cardiac catheterization laboratories. A study was performed to test the prediction capabilities of the Gorlin formula as well as the Aaslid and Gabbay formula for the effective orifice area of prosthetic heart valves. Pressure gradient, flow, and valve opening area measurements were performed on four 27 mm valve prostheses (two mechanical bileaflet designs, St. Jude and Edwards-Duromedics, an Edwards pericardial tissue valve, and a trileaflet polyurethane valve) each mounted in the aortic position of an in vitro pulse duplicator. With the known valve orifice area, a different discharge coefficient was computed for each of the four valves and three orifice area formulas. After some theoretical considerations, it was proposed that the discharge coefficient would be a function of the flow rate through the valve. All discharge coefficients were observed to increase with increasing systolic flow rate. An empirical relationship of discharge coefficient as a linear function of systolic flow rate was determined through a regression analysis, with a different relationship for each valve and each orifice area formula. Using this relationship in the orifice area formulas improved the accuracy of the prediction of the effective orifice area with all three formulas performing equally well.     

An approach to the simulation of fluid-structure interaction in the aortic valve

A pair of finite element models has been employed to study the interaction of blood flow with the operation of the aortic valve. A three-dimensional model of the left ventricle with applied wall displacements has been used to generate data for the spatially and time-varying blood velocity profile across the aortic aperture. These data have been used as the inlet loading conditions in a three-dimensional model of the aortic valve and its surrounding structures. Both models involve fluid-structure interaction and simulate the cardiac cycle as a dynamic event. Confidence in the models was obtained by comparison with data obtained in a pulse duplicator. The results show a circulatory flow being generated in the ventricle which produces a substantially axial flow through the aortic aperture. The aortic valve behaves in an essentially symmetric way under the action of this flow, so that the pressure difference across the leaflets is approximately uniform. This work supports the use of spatially uniform but temporally variable pressure distributions across the leaflets in dry or structural models of aortic valves. The study is a major advance through its use of truly three-dimensional geometry, spatially non-uniform loading conditions for the valve leaflets and the successful modelling of progressive contact of the leaflets in a fluid environment.     

Design of a portable artificial heart drive system based on efficiency analysis

This paper discusses a computer simulation of a pneumatic portable piston-type artificial heart drive system with a linear d-c-motor. The purpose of the design is to obtain an artificial heart drive system with high efficiency and small dimensions to enhance portability. The design employs two factors contributing the total efficiency of the drive system. First, the dimensions of the pneumatic actuator were optimized under a cost function of the total efficiency. Second, the motor performance was studied in terms of efficiency. More than 50 percent of the input energy of the actuator with practical loads is consumed in the armature circuit in all linear d-c-motors with brushes. An optimal design is: the piston cross-sectional area of 10.5 cm2 cylinder longitudinal length of 10 cm. The total efficiency could be up to 25 percent by improving the gasket to reduce the frictional force.     

In vitro hemodynamics and valve imaging in passive beating hearts

Due to their high complexity, surgical approaches to valve repair may benefit from the use of in vitro simulators both for training and for the investigation of those measures which can lead to better clinical results. In vitro tests are intrinsically more effective when all the anatomical substructures of the valvular complexes are preserved. In this work, a mock apparatus able to house an entire explanted porcine heart and subject it to pulsatile fluid-dynamic conditions was developed, in order to enable the hemodynamic analysis of simulated surgical procedures and the imaging of the valvular structures. The mock loop's hydrodynamic design was based on an ad-hoc defined lumped-parameter model. The left ventricle of an entire swine heart was dynamically pressurized by an external computer-controlled pulse duplicator. The ascending aorta was connected to a hydraulic circuit which simulated the input impedance of the systemic circulation; a reservoir passively filled the left atrium. Accesses for endoscopic imaging were located in the apex of the left ventricle and in the aortic root. The experimental pressure and flow tracings were comparable with the typical in vivo curves; a mean flow of 3.5±0.1l pm and a mean arterial pressure of 101±2 mmHg was obtained. High-quality echographic and endoscopic video recordings demonstrated the system's excellent potential in the observation of the cardiac structures dynamics. The proposed mock loop represents a suitable in vitro system for the testing of minimally-invasive cardiovascular devices and surgical procedures for heart valve repair.     

A synthetic fiber-reinforced stentless heart valve

There is strong evidence that failure of bioprosthetic and synthetic valves occurs as a consequence of high tensile and bending stresses, acting on the leaflets during opening and closing. In stented prostheses, whether synthetic or biological, the absence of contraction of the aortic base causes the leaflets to be subjected to an unphysiological degree of flexure, which is also related to calcification. However, a stentless synthetic valve, which has a flexible aorta base, can be a good alternative for stented synthetic valves. Moreover, fiber-reinforcement is assumed to lead to a decrease of tears and perforation as a result of reduced stresses in the weaker parts of the leaflets in their closed configuration. The manufacturing method for a stentless, fiber-reinforced, synthetic valve is presented. Prototypes are tested in a pulse duplicator system. The results show that the mean systolic pressure difference is very low, while the high regurgitation (up to 26%) is probably caused by a too small coaptation area of the leaflets.     

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.     

Computational Phlebology: The Simulation of a Vein Valve

We present a three-dimensional computer simulation of the dynamics of a vein valve. In particular, we couple the solid mechanics of the vein wall and valve leaflets with the fluid dynamics of the blood flow in the valve. Our model captures the unidirectional nature of blood flow in vein valves; blood is allowed to flow proximally back to the heart, while retrograde blood flow is prohibited through the occlusion of the vein by the valve cusps. Furthermore, we investigate the dynamics of the valve opening area and the blood flow rate through the valve, gaining new insights into the physics of vein valve operation. It is anticipated that through computer simulations we can help raise our understanding of venous hemodynamics and various forms of venous dysfunction.     

Estimation of alveolar pressure during forced oscillation of the respiratory system.

A method for obtaining a continuous estimate of alveolar pressure (PAlv) during periodic flow is described; it was developed to improve the precision of measurements of airway and respiratory tissue impedance using the improved resolution of relatively high-frequency (approximately 5 Hz) singlas. The respiratory system was modulated with a piston pump, and lung volume and the volume change due to compression and expansion of alveolar gas were measured plethysmorgraphically; these signals and an analog divider were used to obtain a continuous solution of Boyle's law during flow. The plethysmorgraph was of the "flow" type; with it volume changes at frequencies up to 10 Hz and with rates of change up to 6 l/s were measured without amplitude or phase distortion. The method permits control of frequency and flow amplitude during PAlv measurement and calibration of PAlv in the absence of an active chest wall. However, it is technically complex.     

Evaluation of an aortic valve prosthesis: Fluid-structure interaction or structural simulation?

Bio-inspired polymeric heart valves (PHVs) are excellent candidates to mimic the structural and the fluid dynamic features of the native valve. PHVs can be implanted as prosthetic alternative to currently clinically used mechanical and biological valves or as potential candidate for a minimally invasive treatment, like the transcatheter aortic valve implantation. Nevertheless, PHVs are not currently used for clinical applications due to their lack of reliability. In order to investigate the main features of this new class of prostheses, pulsatile tests in an in-house pulse duplicator were carried out and reproduced in silico with both structural Finite-Element (FE) and Fluid-Structure interaction (FSI) analyses. Valve kinematics and geometric orifice area (GOA) were evaluated to compare the in vitro and the in silico tests. Numerical results showed better similarity with experiments for the FSI than for the FE simulations. The maximum difference between experimental and FSI GOA at maximum opening time was only 5%, as compared to the 46.5% between experimental and structural FE GOA. The stress distribution on the valve leaflets clearly reflected the difference in valve kinematics. Higher stress values were found in the FSI simulations with respect to those obtained in the FE simulation. This study demonstrates that FSI simulations are more appropriate than FE simulations to describe the actual behaviour of PHVs as they can replicate the valve-fluid interaction while providing realistic fluid dynamic results.     

A phrenic nerve-actuated electronically controlled positive-pressure ventilator

We have constructed an electronically controlled positive-pressure ventilator actuated by phrenic neural activity for use in open-chested or paralyzed experimental animals for the study of breathing pattern. A Bird Mark 14 positive-pressure ventilator was modified such that flow is a linear function of a command signal. Flow is delivered by advancing an air valve with a servo-motor that is controlled by one of three different operational modes. In two of the modes, the difference between the electronic average of inspiratory phrenic activity (moving average) and a feedback signal determines the inspiratory flow. The feedback signal is derived from either tracheal pressure or an electronic measure of inspired volume. In the third mode, the moving average is differentiated to provide control of inspiratory flow and volume. Physiological flow profiles were created using all three operational modes. Integration of an air-valve position signal provides an electronic measure of tidal volume. An additional feature of this ventilator allows inspiratory flow and duration to be predetermined for a given breath.     

Manufacturing and hydrodynamic assessment of a novel aortic valve made of a new nanocomposite polymer

Synthetic leaflet heart valves have been widely studied as possible alternatives to the current mechanical and bioprosthetic valves. Assessing the in vitro hydrodynamic function of these prostheses is of great importance to predict their hemodynamic behaviour prior to implantation. This study introduces an innovative concept of a low-profile semi-stented surgical aortic valve (SSAV) made of a novel nanocomposite polyurethane with a polycarbonate soft segment (PCU) and polyhedral oligomeric silsesquioxane (POSS) nanoparticles covalently bonded as a pendant cage to the hard segment. The POSS–PCU is already used in surgical implants, including lacrimal duct, bypass graft, and recently, a tracheal replacement. Nine valves of three leaflet thicknesses (100, 150 and 200 μm) and 21 mm internal diameter were prepared using an automated dip-coating procedure, and assessed in vitro for their hydrodynamic performance on a pulse duplicator system. A commercially available porcine bioprosthetic valve (Epic?, St. Jude Medical) of equivalent size was selected as a control model. Compared to the bioprosthetic valve, the SSAVs showed a considerably lower transvalvular pressure drop and larger effective orifice area (EOA). They were also characterised by a lower systolic energy loss, especially at high cardiac outputs. The leaflet thickness was found to significantly affect the hydrodynamics of these valves (P<0.01). The SSAVs with 100 μm leaflets demonstrated improved flow characteristics compared to the bioprosthetic valve. The enhanced hydrodynamic function of the SSAV suggests that the proposed design together with the advanced POSS–PCU material can represent a significant step towards the introduction of polyurethane valves into the clinical application.     

固定化酶-离子交换组合系统进行青霉素G水解生产6-APA的模型化研究

采用固定化青霉素酰化酶(Penicillin acylase)在反应器中进行青霉素G水解生产6－APA,同时与离子交换柱相组合以连续地去除反应混合液中的苯乙酸。建立了离子变换柱的分格模型(Comparunent model)．在确定了青霉素G和苯乙酸沿柱高的浓度分布的基础上,与描述固定化酶反应器的状态方程相结合,得到了固定化酶－离子交换组合系统的数学模型。在将计算机模拟值与实验值进行验证后,探讨了组合系统中树脂量、循环流速和组合起始时间对青霉素G酶解过程的影响。     

Spirograph for small laboratory animals

A design of dry spirograph is described. It is characterized by greater precision, lack of inertia, high reliability, absence of respiration resistance, adequate form of recording, rapid resetting to any respiratory rate. The device consists of two similar injection syringes, photoelectric sensor for the identification of the initial moments of respiration stages, electromagnetic valves, two photoelectric converters of the air volume into the impulse signal, vacuum micro-pump, microcompressor and a system of air-driving tubes. In the initial position of pistons and valves the microcompressor pumps air into the inhalation cylinder and lifts the piston to the upper extreme position. With the signal marking the beginning of inspiration, the valves switch over and the piston lowers, pushing out the air, which moves into the animals' respiratory organs. Simultaneously, the signals of the inhaled air volume from the photoelectric transducer reach the recorder. During expiration the air pushes the piston down into the second cylinder and photoelectric transducer gives the information on the volume of the expired air.     

超声彩色血流成像的计算机快速仿真方法

研究超声彩色血流成像的快速仿真方法,克服原先仿真方法非常耗时的缺点。方法超声彩色血流成像计算机仿真中,血流信号是对成像区间内所有点散射体的回波信号累加而得到的。通过引入新的等效散射体模型,可以大大降低散射体的密度,从而减少计算回波信号所需时间。在计算机上用Matlab编程来进行仿真实验,对以往仿真方法和基于等效散射体模型方法的性能进行比较。结果实验表明:基于等效散射体模型的仿真,在保证相同流速精度的前提下,仿真速度比传统方法提高了10倍以上。结论基于等效散射体模型的仿真方法能极大地提高超声彩色血流成像的仿真速度,可以为超声彩色血流成像的方法研究提供便利。     

Calculation of mean cell residence time for unsteady-state activated sludge systems

A formulation to calculate the mean cell residence time (MCRT or sludge age) of unsteady-state activated sludge systems is presented. The formulation was studied by applying it to data generated by computer simulation and to data obtained from an actual wastewater treatment plant. The computer simulation study allowed the effects of step and pulse changes in biochemical oxygen demand (BOD) loading, and step changes in a control variable, waste sludge flow rate, to be studied independently of each other and of other disturbances. The unsteady-state MCRT formulation (herein called the dynamic sludge age, or DSA) was found to be an improvement over the traditional steady-state calculation, both for process control, and for research into activated sludge dynamics.