Estimation of arterial compliance in aortic regurgitation: three methods evaluated in pigs

Three methods for measuring arterial compliance when aortic regurgitation is present are examined. The first two methods are based on a Windkessel model composed of two elements, compliance C and resistance R. Arterial compliance was estimated from diastolic pressure waveforms and diastolic regurgitant flow for one method, and from systolic aortic pressure waveforms and systolic flow for the other method. The third method was based on a three-element Windkessel model, composed of characteristic resistance r, compliance C and resistance R. In this method arterial compliance was calculated by adjusting the model to the modulus and phase of the first harmonic term of the aortic input impedance. The three methods were compared and validated in six anaesthetised pigs over a broad range of aortic pressures. The three methods were found to give quantitatively similar estimates of arterial compliance at mean aortic pressures above 60 mm Hg. Below 60 mm Hg, estimates of arterial compliance varied widely, probably because of poor validity of the Windkessel models in the low pressure range.     

人工心泵与循环系统模拟装置的非线性电路模型

目前的循环系统电路模型,由于心脏瓣膜的非线性阻抗特性,收缩期与舒张期要用不同的电路,而瓣膜阻抗从收缩期到舒张期的变化的过渡过程则被忽略了。本文用一个非线性函数描述瓣膜阻抗的时变特性,使得循环系统可以在整个搏动周期内用统一的电路模型描述。对一个模拟循环系统,用此电路模型可以从泵的驱动压用数值计算方法算出泵输出流量和模拟动脉压力波形。将此计算结果与实验测得的相应波形比较,可知瓣膜阻抗变化的过渡过程对系统的行为有明显影响,而本文得出的电路模型可以以令人满意的精度描述此模拟循环系统。     

左心循环系统的建模与仿真

将左心模型与四元件的动脉系统Windkessel模型耦合,构成左心-动脉系统交互的左心循环系统模型.模型包括左心房、左心室、二尖瓣、动脉辩和动脉系统,实现了对左心循环系统的血流动力学模拟.应用状态空间法和SIMULINK框图模型法两种技术和MATLAB工具,进行了数学建模和数值计算,具有模型直观、容易实现、方便调节参数等优点.应用这一仿真模型,可以对左心室容积、血压及主动脉血压和血流等进行动态模拟.仿真结果与生理实际情况相符.     

新鲜主动脉瓣与肺动脉瓣的解剖学观测及其临床意义

目的：从解剖学方面为自体肺动脉瓣替换主动脉瓣手术提供理论依据。方法：对１１例正常国人新鲜心脏标本的主、肺动脉瓣进行解剖学测量,并对结果进行对比研究。结果：①肺动脉瓣所能承受的压力虽小于主动脉瓣所能承受的压力,但其最小值（２８ｋＰａ）高于正常人体动脉压;②肺动脉瓣及肺动脉窦的各项测量数值均略大于主动脉瓣及主动脉窦,但无统计学意义（Ｐ＞０．０５）。结论：①肺动脉瓣能承受主动脉瓣位置的压力;②主、肺动脉瓣叶及主、肺动脉窦在形态、大小上是匹配的。     

The closing behavior of mechanical aortic heart valve prostheses

Mechanical artificial heart valves rely on reverse flow to close their leaflets. This mechanism creates regurgitation and water hammer effects that may form cavitations, damage blood cells, and cause thromboembolism. This study analyzes closing mechanisms of monoleaflet (Medtronic Hall 27), bileaflet (Carbo-Medics 27; St. Jude Medical 27; Duromedics 29), and trileaflet valves in a circulatory mock loop, including an aortic root with three sinuses. Downstream flow field velocity was measured via digital particle image velocimetry (DPIV). A high speed camera (PIVCAM 10-30 CCD video camera) tracked leaflet movement at 1000 frames/s. All valves open in 40-50 msec, but monoleaflet and bileaflet valves close in much less time (< 35 msec) than the trileaflet valve (>75 msec). During acceleration phase of systole, the monoleaflet forms a major and minor flow, the bileaflet has three jet flows, and the trileaflet produces a single central flow like physiologic valves. In deceleration phase, the aortic sinus vortices hinder monoleaflet and bileaflet valve closure until reverse flows and high negative transvalvular pressure push the leaflets rapidly for a hard closure. Conversely, the vortices help close the trileaflet valve more softly, probably causing less damage, lessening back flow, and providing a washing effect that may prevent thrombosis formation.     

Engineering analysis of the effects of bulging sinuses in a newly designed pediatric pulmonary heart valve on hemodynamic function

The purpose of this study was to examine the hemodynamic characteristics of expanded polytetrafluoroethylene (ePTFE) pulmonary valves with bulging sinuses quantitatively in a pediatric pulmonary mechanical circulatory system designed by us, in order to propose the optimal design for clinical applications. In this study, we developed a pediatric pulmonary mock circulation system, which consisted of a pneumatic right ventricular model, a pulmonary heart valve chamber, and a pulmonary elastic compliance tubing with resistive units. The hemodynamic characteristics of four different types of ePTFE valves and a monoleaflet mechanical heart valve were examined. Relationships between the leaflet movements and fluid characteristics were evaluated based on engineering analyses using echocardiography and a high-speed video camera under the pediatric circulatory conditions of the mock system. We successfully performed hemodynamic simulations in our pediatric pulmonary circulatory system that could be useful for quantitatively evaluating the pediatric heart valves. In the simulation study, the ePTFE valve with bulging sinuses exhibited a large eddy in the vicinity of the leaflets, whereas the straight tubing exhibited turbulent flow. The Reynolds number obtained in the valve with bulging sinuses was calculated to be 1667, which was smaller than that in the straight tubing (R (e) = 2454).The hemodynamic characteristics of ePTFE pediatric pulmonary heart valves were examined in our mock circulatory system. The presence of the bulging sinuses in the pulmonary heart valve decreased the hydrodynamic energy loss and increased the systolic opening area. Based on an in vitro experiment, we were able to propose an optimal selection of pulmonary valve design parameters that could yield a more sophisticated pediatric ePTFE valve shape.     

Three-dimensional numeric simulation of flow through an aortic bileaflet valve in a realistic model of aortic root

A three-dimensional, realistic model of an aortic mechanical heart valve and Valsalva sinuses was developed to predict, by means of a numerical time dependent simulation, the flow field during a fraction of the systolic period. The numeric simulation was performed upon a model of valve similar to a Carbomedics 27 mm placed in a physiologic aortic root shaped model, in which no symmetry planes were exploited to reach a more realistic level. Input data for the simulation have been acquired during an experimental session on the same valve, according to the guidelines of testing protocol for prosthetic heart valves. Flow was assumed to be Newtonian and laminar at low regime and the leaflets fixed in the fully open position. The forward flow of the systolic phase was investigated, and a comparison with experimental results was performed at peak systole, the most representative point of the cardiac cycle. The results of this simulation furnished a reasonable indication (in terms of fluid dynamics) parameters downstream of the prosthetic device, especially in Valsalva sinuses, the role of which is proven to affect the valve's performance.     

6-Month aortic valve implantation of an off-the-shelf tissue-engineered valve in sheep

Diseased aortic valves often require replacement, with over 30% of the current aortic valve surgeries performed in patients who will outlive a bioprosthetic valve. While many promising tissue-engineered valves have been created in the lab using the cell-seeded polymeric scaffold paradigm, none have been successfully tested long-term in the aortic position of a pre-clinical model. The high pressure gradients and dynamic flow across the aortic valve leaflets require engineering a tissue that has the strength and compliance to withstand high mechanical demand without compromising normal hemodynamics. A long-term preclinical evaluation of an off-the-shelf tissue-engineered aortic valve in the sheep model is presented here. The valves were made from a tube of decellularized cell-produced matrix mounted on a frame. The engineered matrix is primarily composed of collagen, with strength and organization comparable to native valve leaflets. In vitro testing showed excellent hemodynamic performance with low regurgitation, low systolic pressure gradient, and large orifice area. The implanted valves showed large-scale leaflet motion and maintained effective orifice area throughout the duration of the 6-month implant, with no calcification. After 24 weeks implantation (over 17 million cycles), the valves showed no change in tensile mechanical properties. In addition, histology and DNA quantitation showed repopulation of the engineered matrix with interstitial-like cells and endothelialization. New extracellular matrix deposition, including elastin, further demonstrates positive tissue remodeling in addition to recellularization and valve function. Long-term implantation in the sheep model resulted in functionality, matrix remodeling, and recellularization, unprecedented results for a tissue-engineered aortic valve.     

The influence of mock circulation input impedance on valve acceleration during in vitro cardiac device testing

For a mechanical heart valve, a strong spike in pressure during closing is associated with valve wear and erythrocyte damage; thus, for valid in vitro testing, the mock circulation system should replicate the conditions, including pressure spikes, expected in vivo. To address this issue, a study was performed to investigate how mock circulation input impedance affects valve closure dynamics. A left ventricular model with polyurethane trileaflet inflow valve and tilting disc outflow valve was connected to a Louisville mock circulation system, which incorporates 2 adjustable flow resistors and 2 compliances. In the study, 116 cases matched zero frequency modulus well (982-1147 dyn x s/cm), but higher harmonics were purposely varied. Acceleration measured at the outflow valve ring (42.4-89.4 milli-Gs) was uncorrelated with impedance error (74.1-237 dyn x s/cm relative to target impedance), but was correlated with end-systolic impedance (1082-1319 dyn x s/cm) for cases with high zero frequency modulus, which exhibited just less than full ejection. These differences demonstrate that mock circulation response affects the magnitude of the closing spike, indicating that control of this parameter is necessary for authentic testing of valves. Correlation of acceleration to end-systolic impedance was weak for low zero frequency modulus, which tended toward full or hyperejection, reinforcing common laboratory observations that valve closing also depends on ventricular operating conditions.     

Development of aortic and mitral valve continuity in the human embryonic heart

The anatomic relationship of the aortic and mitral valves is a useful landmark in assessing congenital heart malformations. The atrioventricular and semilunar valve regions originate in widely separated parts of the early embryonic heart tube, and the process by which the normal fibrous continuity between the aortic and mitral valves is acquired has not been clearly defined. The development of the aortic and mitral valve relationship was studied in normal human embryos in the Carnegie Embryological Collection, and specimens of Carnegie stages 13, 15, 17, 19, and 23, prepared as serial histologic sections cut in the sagittal plane, were selected for reconstruction. In stage 13, the atrioventricular valve area is separated from the semilunar valve area by the large bend between the atrioventricular and outflow-tract components of the single lumen heart tube created by the left interventricular sulcus. In stages 15 and 17, the aortic valve rotates into a position near the atrioventricular valves with development of four chambers and a double circulation. In stage 19, there is fusion of aortic and mitral endocardial cushion material along the endocardial surface of the interventricular flange, and this relationship is maintained in subsequent stages. Determination of three-dimensional Cartesian coordinates of the midpoints of valve positions shows that, while there is growth of intervalvular distances up to stage 17, the aortic to mitral distance is essentially unchanged thereafter. During the period studied, the left ventricle increases in length over threefold. The relative lack of growth in the saddle-shaped fold between the atrioventricular and outflow tract components of the heart, contrasting with the rapid growth of the outwardly convex components of most of the atrial and ventricular walls, may be attributed to the different mechanical properties of the two configurations. It is postulated that the pathogenesis of congenital heart malformations, which characteristically have failure of development of aortic and mitral valve continuity, may involve abnormalities of rotation of the aortic region or malpositioning of the fold in the heart tube.     

Characterization of an adult mock circulation for testing cardiac support devices

A need exists for a mock circulation that behaves in a physiologic manner for testing cardiac devices in normal and pathologic states. To address this need, an integrated mock cardiovascular system consisting of an atrium, ventricle, and systemic and coronary vasculature was developed specifically for testing ventricular assist devices (VADs). This test configuration enables atrial or ventricular apex inflow and aortic outflow cannulation connections. The objective of this study was to assess the ability of the mock ventricle to mimic the Frank-Starling response of normal, heart failure, and cardiac recovery conditions. The pressure-volume relationship of the mock ventricle was evaluated by varying ventricular volume over a wide range via atrial (preload) and aortic (afterload) occlusions. The input impedance of the mock vasculature was calculated using aortic pressure and flow measurements and also was used to estimate resistance, compliance, and inertial mechanical properties of the circulatory system. Results demonstrated that the mock ventricle pressure-volume loops and the end diastolic and end systolic pressure-volume relationships are representative of the Starling characteristics of the natural heart for each of the test conditions. The mock vasculature can be configured to mimic the input impedance and mechanical properties of native vasculature in the normal state. Although mock circulation testing systems cannot replace in vivo models, this configuration should be well suited for developing experimental protocols, testing device feedback control algorithms, investigating flow profiles, and training surgical staff on the operational procedures of cardiovascular devices.     

Development and characterization of tissue-engineered aortic valves

Tissue-engineered aortic valves, known as recellularized heart valves, were developed by seeding human neonatal fibroblasts onto decellularized, porcine aortic valves. Recellularized heart valves were cultured up to 8 weeks in a novel bioreactor that imposed dynamic pulsatile fluid flow to expose the dermal fibroblasts to mechanical forces. Our data showed that, under static or dynamic flow conditions, dermal fibroblasts attached to and migrated into the decellularized, porcine valve scaffolding. The human cells remained viable as indicated by MTT viability staining. Gradual colonization of the decellularized porcine scaffolding by the human dermal fibroblasts was shown histologically by hematoxylin & eosin staining, immunocytochemically using a monoclonal antibody directed against prolyl-4-hydroxylase (an intracellular enzyme expressed by human fibroblasts synthesizing collagen), and quantitative digital image analyses. Thymidine and proline radiolabeled analog studies at 1, 2 and 4 weeks of individual leaflets cultured statically demonstrated that the human fibroblasts were mitotic and synthesized human extracellular matrix proteins, thereby supplementing the existing porcine matrix. The overall approach results in a heart valve populated with viable human cells. In the development of valves that perform in a similar manner as natural biological structures, this approach may present some unique benefits over current medical therapies.     

Automatic detection of sounds and murmurs in patients with lonescu-Shiley aortic bioprostheses

The problems encountered in the automatic detection of cardiac sounds and murmurs are numerous. The phonocardiogram (PCG) is a complex signal produced by deterministic events such as the opening and closing of the heart valves, and by random phenomena such as blood-flow turbulence. In addition, background noise and the dependence of the PCG on the recording sites render automatic detection a difficult task. In the paper we present an iterative automatic detection algorithm based on the a priori knowledge of spectral and temporal characteristics of the first and second heart sounds, the valve opening clicks, and the systolic and diastolic murmurs. The algorithm uses estimates of the PCG envelope and noise level to identify iteratively the position and duration of the significant acoustic events contained in the PCG. The results indicate that it is particularly effective in detecting the second heart sound and the aortic component of the second heart sound in patients with lonescu-Shiley aortic valve bioprostheses. It has also some potential for the detection of the first heart sound, the systolic murmur and the diastolic murmur.     

Patient-Specific Modeling of Blood Flow and Pressure in Human Coronary Arteries

Coronary flow is different from the flow in other parts of the arterial system because it is influenced by the contraction and relaxation of the heart. To model coronary flow realistically, the compressive force of the heart acting on the coronary vessels needs to be included. In this study, we developed a method that predicts coronary flow and pressure of three-dimensional epicardial coronary arteries by considering models of the heart and arterial system and the interactions between the two models. For each coronary outlet, a lumped parameter coronary vascular bed model was assigned to represent the impedance of the downstream coronary vascular networks absent in the computational domain. The intramyocardial pressure was represented with either the left or right ventricular pressure depending on the location of the coronary arteries. The left and right ventricular pressure were solved from the lumped parameter heart models coupled to a closed loop system comprising a three-dimensional model of the aorta, three-element Windkessel models of the rest of the systemic circulation and the pulmonary circulation, and lumped parameter models for the left and right sides of the heart. The computed coronary flow and pressure and the aortic flow and pressure waveforms were realistic as compared to literature data.     

Qualitative haemodynamic validation of a percutaneous temporary aortic valve: a proof of concept study

The concept of temporary aortic valves has been suggested in the clinical settings of acute aortic regurgitation and transcatheter aortic valve replacement procedure (TAVR). In TAVR, suggestions have been made to pre-treat or remove the diseased aortic valve prior to implantation of the replacement valve. A successful temporary aortic valve must demonstrate the ability to prevent life-threatening haemodynamics of massive aortic regurgitation. A novel temporary aortic valve (TAV) design, comprised of inflatable balloon elements as a check-valve, can readily be deployed and retrieved via a catheter-system. A simple flow model is set up to test the TAV's performance in severe aortic regurgitation. With induced aortic regurgitation, placement of the TAV is found to increase the distal aortic diastolic pressure, to reduce the widened pulse pressure, to protect proximal aorta-left ventricle from diastolic pressure elevation and to reduce the aortic regurgitant volume. In conclusion, continued development of the TAV system can lead to a successful temporary aortic valve to be used in various appropriate clinical settings.     

Mechanical heart valve performance in a pulsatile pediatric ventricular assist device

A pulsatile pediatric ventricular assist device with a dynamic stroke volume of 12 ml is currently under development at the Pennsylvania State University. A monoleaflet valve (Bj?rk-Shiley Monostrut) and a bileaflet valve (CPHV, CarboMedics Prosthetic Heart Valve) were examined in this study. A high-speed video and data acquisition system was used to simultaneously record video images, pressure waveforms, and flow waveforms for an array of in vitro test conditions that varied heart rate and systolic duration. The CPHV in both the horizontal and vertical orientations have larger regurgitant volumes than the Monostrut valves at all operating conditions in both the inlet and outlet positions. However, the CPHV has higher stroke volumes and cardiac outputs than the Monostrut valve at higher heart rates and longer systolic durations. In addition, the hydrodynamic performance of the Monostrut valve is more sensitive to changes in operating conditions for the pulsatile pediatric ventricular assist device than the CPHV in both orientations. Additional testing is under way to identify the optimal operating conditions for each type of valve.     

Mechanisms of the in vivo inhibition of calcification of bioprosthetic porcine aortic valve cusps and aortic wall with triglycidylamine/mercapto bisphosphonate

Heart valve replacements fabricated from glutaraldehyde (Glut)-crosslinked heterograft materials, porcine aortic valves or bovine pericardium, have been widely used in cardiac surgery to treat heart valve disease. However, these bioprosthetic heart valves often fail in long-term clinical implants due to pathologic calcification of the bioprosthetic leaflets, and for stentless porcine aortic valve bioprostheses, bioprosthetic aortic wall calcification also typically occurs. Previous use of the epoxide-based crosslinker, triglycidyl amine (TGA), on cardiac bioprosthetic valve materials demonstrated superior biocompatibility, mechanics, and calcification resistance for porcine aortic valve cusps (but not porcine aortic wall) and bovine pericardium, vs. Glut-prepared controls. However, TGA preparation did not completely prevent long-term calcification of cusps or pericardium. Herein we report further mechanistic investigations of an added therapeutic component to this system, 2-mercaptoethylidene-1,1-bisphosphonic acid (MABP), a custom synthesized thiol bisphosphonate, which has previously been shown in a preliminary report to prevent bioprosthetic heterograft biomaterial calcification when used in combination with initial TGA crosslinking for 7 days. In the present studies, we have further investigated the effectiveness of MABP in experiments that examined: (1) The use of MABP after optimal TGA crosslinking, in order to avoid any competitive interference of MABP-reactions with TGA during crosslinking; (2) Furthermore, recognizing the importance of alkaline phosphatase (ALP) in the formation of dystrophic calcific nodules, we have investigated the hypothesis that the mechanism by which MABP primarily functions is through the reduction of ALP activity. Results from cell-free model systems, cell culture studies, and rat subcutaneous implants, show that materials functionalized with MABP after TGA crosslinking have reduced ALP activity, and in vivo have no significant calcification in long-term implant studies. It is concluded that bioprosthetic heart valves prepared in this fashion are compelling alternatives for Glut-prepared bioprostheses.     

Vascular characteristics influence the aortic ultrasound Doppler signal: computer and hydraulic model simulations

There is an increasing demand for non-invasive methods for the assessment of left ventricular function. Ultrasound Doppler methods are promising, and the early systolic flow velocity signal immediately distal to the aortic valve has been used clinically for this purpose. However, the signal is influenced not only by left ventricular ejection but also by systemic vascular characteristics. Their relative contribution to the timevelocity signal has not been analysed in depth previously. A theoretical analysis, based on a three-element Windkessel model, neglecting peripheral outflow in early systole and assuming linear pressure rise, was therefore tested in computer and hydraulic model simulations where peripheral outflow was included. Significant changes in early aortic flow velocity parameters were found when vascular characteristics were altered. As predicted by the theory, with a standardized aortic valve area and aortic pressure change, the simulations confirmed that maximal flow velocity is related to compliance of the aorta and the large arteries, and that maximal acceleration is inversely related to the characteristic impedance of the aorta. Therefore, maximal velocity and acceleration can be used for assessment of left ventricular function only in situations where vascular characteristics can be considered relatively constant or where they can be estimated.     

Dynamic particle image velocimetry study of the aortic flow field of contemporary mechanical bileaflet prostheses

The characteristics of mechanical bileaflet valves, the leaflets of which open at the outside first, differ significantly from those of natural valves, whose leaflets open at the center first, and this fact affects the flow field down-stream of the valves. The direction of jet-type flows, which is influenced by this difference in valve features, and the existence of the sinus of Valsalva both affect the flow field inside the aorta in different ways, depending on the valve design. There may also be an influence on the coronary circulation, the entrance to which resides inside the sinus of Valsalva. A dynamic particle image velocimetry (PIV) study was conducted to analyze the influence of the design of prosthetic heart valves on the aortic flow field. Three contemporary bileaflet prostheses, the St. Jude Medical (SJM) valve, the On-X valve (with straight leaflets), and the MIRA valve (with curved leaflets), were tested inside a simulated aorta under pulsatile flow conditions. A dynamic PIV system was employed to analyze the aortic flow field resulting from the different valve designs. The two newer valves, the On-X and the MIRA valves, open more quickly than the SJM valve and provide a wider opening area when the valve is fully open. The SJM valve's outer orifices deflect the flow during the accelerating flow phase, whereas the newer designs deflect the flow less. The flow through the central orifice of the SJM valve has a lower velocity compared to the newer designs; the newer designs tend to have a strong flow through all orifices. The On-X valve generates a simple jet-type flow, whereas the MIRA valve (with circumferentially curved leaflets) generates a strong but three-dimensionally diffuse flow, resulting in a more complex flow field downstream of the aortic valve. The clinically more adapted 180 degrees orientation seems to provide a less diffuse flow than the 90 degrees orientation does. The small differences in leaflet design in the bileaflet valves generate noticeable differences in the aortic flow; the newer valves show strong flows through all orifices.     

一种模拟血液循环系统实验研究

目的 研究一种能够准确复现人体血流动力学环境的模拟血液循环系统（mock circulation system,MCS）用于心室辅助装置（ventricular assist device, VAD）、人工心肺机等人工器官研发过程中的体外测试。方法 建立一套包括体肺循环的双心驱动MCS,基本涵盖心血管系统的主要生理特征及功能,其中对瓣膜和动脉的模拟提出采用硅胶材料制作的新方式。该系统可以通过调整控制系统参数或结构参数来模拟正常人体、心衰、瓣膜疾病、动脉硬化以及外周阻性变化等多种生理环境,并利用传感器与控制系统实现压力、流量的实时显示、控制和数据保存。结果 该MCS模拟正常人体和多种病症下的血流动力学环境均与人体实际情况基本一致。并且新的瓣膜和动脉模拟方式减小了压力波动,使模拟效果更好。在模拟心衰病症下使用航天泰心HeartCon型VAD接入系统,可以看到其血流动力学环境（主动脉压力、左心室压力、心排量等）均能恢复到正常范围。结论 该MCS能够准确复现多种生理状态下体肺循环的血流动力学环境,为VAD等人工器官的性能测试和控制策略的设计提供有效的实验平台。同时,采用硅胶材料制作瓣膜和动脉的模拟方式也可以作为MCS研究中的新思路进一步完善。