Several works have separated the pressure waveform p in systemic arteries into reservoir p r and excess p exc components, p = p r + p exc , to improve pulse wave analysis, using windkessel models to calculate the reservoir pressure. However, the mechanics underlying this separation and the physical meaning of p r and p exc have not yet been established. They are studied here using the time-domain, inviscid and linear one-dimensional (1-D) equations of blood flow in elastic vessels. Solution of these equations in a distributed model of the 55 larger human arteries shows that p r calculated using a two-element windkessel model is space-independent and well approximated by the compliance-weighted space-average pressure of the arterial network. When arterial junctions are well-matched for the propagation of forward-travelling waves, p r calculated using a three-element windkessel model is space-dependent in systole and early diastole and is made of all the reflected waves originated at the terminal (peripheral) reflection sites, whereas p exc is the sum of the rest of the waves, which are obtained by propagating the left ventricular flow ejection without any peripheral reflection. In addition, new definitions of the reservoir and excess pressures from simultaneous pressure and flow measurements at an arbitrary location are proposed here. They provide valuable information for pulse wave analysis and overcome the limitations of the current two- and three-element windkessel models to calculate p r .
It was in the year 2000, at the turn of the 21st century, my original idea to establish a forum for cardiovascular engineering professionals finally came to fruition. On the invitation of Kluwer Academic Press, the first issue of Cardiovascular Engineering: an International Journal began exactly a decade ago and it was an exciting moment. It has been an endeavor that has taken considerable effort and energy in maintaining timely publications of high quality articles in my role as the Editor-in-chief and in the fulfillment of the many authors’ sense of accomplishment, seeing their research in print of a refereed journal. The Journal was aimed at providing a forum to promote an international scholarly exchange among scientists, clinicians and biomedical engineers with a common interest in the cardiovascular field and with a particular emphasis on the utilization of quantitative and technological methodologies. As such, the Editorial Board members were recommended from nations in North and South America, Asia and Europe. For any new journal to be longstanding and profitable for the publisher, a professional society affiliation is often necessary. Our Journal did not have this leisure. And it came half a decade later, after Springer took over Kluwer, to include the Journal in major citation bodies and providing us with paperless Electronic Manager for manuscript reviews. It has been the contributions from the many authors, as well as the capable effort of some of the editors, production editors and editorial assistants that made uninterrupted quarterly publication of the Journal possible over the decade. In my appreciation, and if I could name a few individual Editorial Board members of their contributions, the late Prof. Leslie Geddes, the Presidential Medal of Technology recipient, would be the first. Known as the ‘‘Father of Cardiovascular Engineering’’, he paved the growth of the field of cardiovascular engineering for several decades. He gave his best support to the Journal and consistently contributing articles of new advances in technology for combating heart disease. We should all marvel his high energy and achievement. Prof. Abraham Noordergraaf, known as the ‘‘Father of Cardiovascular System Dynamics’’ has energized his European collaborators in making contributions to the Journal. Prof. YC Fung, known as the ‘‘Father of Biomechanics’’, has been a kind supporter of the Journal in its inception. So are the continued support from Dr. Peter Kerkhof, Dr. Max Valentinuzzi and Dr. John Clark. Guest editors of the Special Issues which have received high marks were attributed to the wonderful work of Dr. Jerry Batzel and his colleagues from the University of Graz. I had planned to serve as the Editor-in-chief for just a few years, but it quickly turned into a decade. It is time for me to move on to publish my own research work in other highly ranked journals which have missed many of my publications in the past decade, as I chose to publish in Cardiovascular Engineering. I will also return to concentrate on my longneglected fondness of writing books. I will embark on new adventures of writing on exciting topics, and to continue to serve as World Scientific Publishers’ Editor-in-Chief of Bioengineering and Biomedical Engineering Book Series.
The rate of biosynthesis and turnover of the plasma protein fibrinogen is a marker of metabolic signaling in aging and disease. The rate in the young normal human subject of 0.260 mg/ml/24 h increases to 0.378 in older normal subjects and to 0.466 in age matched coronary thrombosis patients measured by endogenous labeling of fibrinogen with L: -glutamic acid-C14. The increased rate of fibrinogen turnover has been traced to generation of fibrin by labeling the polymers with glycine C14 ethyl esters in the presence of activated fibrin stabilizing factor. Circulating fibrin increased 520% above normal in ischemic thrombotic cerebrovascular disease. Long chain saturated free fatty acids (FFA) exercise not only primary control over incorporation of Cl4 labeled amino acids into the fibrinogen structure but also activate the cascade sequence of reactions which convert fibrinogen into occlusive fibrin polymers. FFA are normally bound and transported by plasma albumin to mitochondrial sites of energy metabolism. Albumin synthesis declines with aging. This decline is associated with increased plasma levels of FFA resulting in an increase in the plasma FFA/albumin ratio. Correction of this ratio in vitro by restoration of a normal FFA/albumin ratio restores a normal level of fibrinogen synthesis by human hepatocytes.
In this paper, we present design, fabrication and coupled multifield analysis of hollow out-of-plane silicon microneedles with piezoelectrically actuated microfluidic device for transdermal drug delivery (TDD) system for treatment of cardiovascular or hemodynamic disorders such as hypertension. The mask layout design and fabrication process of silicon microneedles and reservoir involving deep reactive ion etching (DRIE) is first presented. This is followed by actual fabrication of silicon hollow microneedles by a series of combined isotropic and anisotropic etching processes using inductively coupled plasma (ICP) etching technology. Then coupled multifield analysis of a MEMS based piezoelectrically actuated device with integrated silicon microneedles is presented. The coupledfield analysis of hollow silicon microneedle array integrated with piezoelectric micropump has involved structural and fluid field couplings in a sequential structural-fluid analysis on a three-dimensional model of the microfluidic device. The effect of voltage and frequency on silicon membrane deflection and flow rate through the microneedle is investigated in the coupled field analysis using multiple code coupling method. The results of the present study provide valuable benchmark and prediction data to fabricate optimized designs of the silicon hollow microneedle based microfluidic devices for transdermal drug delivery applications.
A clinical comparison, of two methods of afterload assessment, has been made. The first method, systemic vascular resistance index (SVR(i)), is based upon the traditional formula for afterload which utilizes central venous pressure (CVP), as well as cardiac index (C(i)), and mean arterial blood pressure (MAP). The second method, total systemic vascular resistance index (TSVR(i)), also uses MAP and C(i). However, TSVR(i) ignores the contribution of CVP. This preliminary examination, of 10 randomly-selected ICU patients, has shown a high degree of correlation (ranging from 90 to 100%) between SVR(i) and TSVR(i) (P < 0.0001). Furthermore, there was also a high degree of correlation (ranging from 94 to 100%) noted between the hour-to-hour change in SVR(i) with the hour-to-hour change in TSVR(i) (P < 0.0001). The results, of this pilot study, support the premise that the use of CVP may not always be necessary for afterload evaluation in the clinical setting. Minimally-invasive means of measuring both C(i) and MAP, without CVP, may be adequate for use in assessing afterload.
This report describes a multi-disciplinary program to develop a pediatric blood pump, motivated by the critical need to treat infants and young children with congenital and acquired heart diseases. The unique challenges of this patient population require a device with exceptional biocompatibility, miniaturized for implantation up to 6 months. This program implemented a collaborative, prescriptive design process, whereby mathematical models of the governing physics were coupled with numerical optimization to achieve a favorable compromise among several competing design objectives. Computational simulations of fluid dynamics, electromagnetics, and rotordynamics were performed in two stages: first using reduced-order formulations to permit rapid optimization of the key design parameters; followed by rigorous CFD and FEA simulations for calibration, validation, and detailed optimization. Over 20 design configurations were initially considered, leading to three pump topologies, judged on the basis of a multi-component analysis including criteria for anatomic fit, performance, biocompatibility, reliability, and manufacturability. This led to fabrication of a mixed-flow magnetically levitated pump, the PF3, having a displaced volume of 16.6 cc, approximating the size of a AA battery and producing a flow capacity of 0.3–1.5 L/min. Initial in vivo evaluation demonstrated excellent hemocompatibility after 72 days of implantation in an ovine. In summary, combination of prescriptive and heuristic design principles have proven effective in developing a miniature magnetically levitated blood pump with excellent performance and biocompatibility, suitable for integration into chronic circulatory support system for infants and young children; aiming for a clinical trial within 3 years.
The regulation of valvular endothelial phenotypes by the hemodynamic environments of the human aortic valve is poorly understood. The nodular lesions of calcific aortic stenosis (CAS) develop predominantly beneath the aortic surface of the valve leaflets in the valvular fibrosa layer. However, the mechanisms of this regional localization remain poorly characterized. In this study, we combine numerical simulation with in vitro experimentation to investigate the hypothesis that the previously documented differences between valve endothelial phenotypes are linked to distinct hemodynamic environments characteristic of these individual anatomical locations. A finite-element model of the aortic valve was created, describing the dynamic motion of the valve cusps and blood in the valve throughout the cardiac cycle. A fluid mesh with high resolution on the fluid boundary was used to allow accurate computation of the wall shear stresses. This model was used to compute two distinct shear stress waveforms, one for the ventricular surface and one for the aortic surface. These waveforms were then applied experimentally to cultured human endothelial cells and the expression of several pathophysiological relevant genes was assessed. Compared to endothelial cells subjected to shear stress waveforms representative of the aortic face, the endothelial cells subjected to the ventricular waveform showed significantly increased expression of the “atheroprotective” transcription factor Kruppel-like factor 2 (KLF2) and the matricellular protein Nephroblastoma overexpressed (NOV), and suppressed expression of chemokine Monocyte-chemotactic protein-1 (MCP-1). Our observations suggest that the difference in shear stress waveforms between the two sides of the aortic valve leaflet may contribute to the documented differential side-specific gene expression, and may be relevant for the development and progression of CAS and the potential role of endothelial mechanotransduction in this disease.
The objective of this study is to develop a model of the cardiovascular system capable of simulating the normal operation of the systemic and pulmonary circulation, starts from aorta, and follows by upper and lower extremities vessels, finally ends with pulmonary veins. The model consists of a closed loop lumped elements with 43 compartments representing the cardiovascular system. The model parameters have been extracted from the literature. Using MATLAB software, the mathematical model has been simulated for the cardiovascular system. Each compartment includes a Resistor-Inductor-Capacitor (RLC) segment. The normal cardiovascular operation is characterised by the pressure–volume curves in different parts of the system. Model verification is performed by comparing the simulation results with the clinical observation reported in the literature. The described model is a useful tool in studying the physiology of cardiovascular system, and the related diseases. Also, it could be a great tool to investigate the effects of the pathologies of the cardiovascular system.
The aim of this study is to describe a robust unified framework for segmentation of the phonocardiogram (PCG) signal sounds based on the false-alarm probability (FAP) bounded segmentation of a properly calculated detection measure. To this end, first the original PCG signal is appropriately pre-processed and then, a fixed sample size sliding window is moved on the pre-processed signal. In each slid, the area under the excerpted segment is multiplied by its curve-length to generate the Area Curve Length (ACL) metric to be used as the segmentation decision statistic (DS). Afterwards, histogram parameters of the nonlinearly enhanced DS metric are used for regulation of the α-level Neyman-Pearson classifier for FAP-bounded delineation of the PCG events. The proposed method was applied to all 85 records of Nursing Student Heart Sounds database (NSHSDB) including stenosis, insufficiency, regurgitation, gallop, septal defect, split sound, rumble, murmur, clicks, friction rub and snap disorders with different sampling frequencies. Also, the method was applied to the records obtained from an electronic stethoscope board designed for fulfillment of this study in the presence of high-level power-line noise and external disturbing sounds and as the results, no false positive (FP) or false negative (FN) errors were detected. High noise robustness, acceptable detection-segmentation accuracy of PCG events in various cardiac system conditions, and having no parameters dependency to the acquisition sampling frequency can be mentioned as the principal virtues and abilities of the proposed ACL-based PCG events detection-segmentation algorithm.
The aim of this study is to detect Acute Hypotensive Episodes (AHE) and Mean Arterial Pressure Dropping Regimes (MAPDRs) using ECG signal and Arterial Blood Pressure waveforms. To meet this end, the QRS complexes and end-systolic end-diastolic pulses are first extracted using two innovative Modified Hilbert Transform-Based algorithms namely as ECGMHT and BPMHT. A new smoothing algorithm is next developed based on piecewise polynomial fitting to smooth the fast fluctuations observed in RR-tachogram, systolic blood pressure (SBP) and diastolic blood pressure (DBP) trends. Afterwards, in order to consider the mutual influence of parameters on the evaluation of shock probability, a Sugeno Adaptive Network-based Fuzzy Inference System-ANFIS is trained using Hasdai et al. (J Am Coll Cardiol, 35: 136–143, 2000) parameters as input, with appropriate membership functions for each parameter. Using this network, it will be possible to incorporate the possible mutual influences between risk parameters such as heart rate, SBP, DBP, ST-segment episodes, age, gender, weight and some miscellaneous factors to the calculation of shock occurrence probability. In the next step, the proposed algorithm is applied to 15 subjects of the MIMIC II Database and AHE and MAPDRs (MAP ≤ 60 mmHg with a period of 30 min or more) are identified. As a result of this study, for a sequence of MAPDRs as long as 20 min or more, there will exist a consequent high peak with the duration of 3–4 min in the corresponding probability of cardiogenic shock diagram.
Similar pulse pressure increases and flow reductions have been reported by many investigators, despite dissimilar forms of arterial loading applied. Increased vascular load is most commonly observed due to mechanical and vasoactive interventions. The present study intended to differentiate the hemodynamic contributions of these two forms of arterial loading at closely matched blood pressure levels. To accomplish this, proximal aortic characteristic impedance (Z(o)), total arterial compliance (C), peripheral vascular resistance (R(s)) and time-domain resolved forward (P(f)) and reflected (P(r)) waves were obtained in six anesthetized, thoracotomized and ventilated dogs. Acute loading was accomplished by brief descending thoracic aorta (DTA) occlusion or by intravenous bolus infusion of methoxamine (MTX:5 mg/ml) Systolic pressure increases were matched to a similar extent. Results showed that pulse pressures were drastically increased, reflecting large increases in wave reflections and decreases in arterial compliances. Changes in Z(o), R(s) and C were quantitatively different between the two forms of loading. DTA occlusion primarily increased Z(o) and R(s) with a concurrently large reduction in C. MTX infusion significantly increased small vessel R(s) to the same extent as DTA occlusion, but with a slight decrease in C secondary to an increase in pressure, with Z(o) unchanged. Examination of dynamic loading showed similar increases in reflection coefficients, but P(f) and P(r) were qualitatively different. We conclude that vasoactive methoxamine infusion provides primarily an increased resistive load, while mechanical DTA occlusion provides an increased complex load to the left ventricle. These loads also occur earlier and variably during ventricular ejection.
The multiscale time irreversibility (MTI) involves the lack of consistency in the properties of a time series if one reverses the reading direction along the time. To analyze the RR time series at rest and during aerobic exercise through the MTI, both in healthy people and cardiac patients. The heartbeat signal was recorded beat to beat for 15 min at rest and 15 min while pedalling on a static bicycle in 10 healthy and active men (age 26.5 ± 3.3 years; height 179.3 ± 6.6 cm; weight 80.4 ± 11.8 kg) and 10 cardiac patients (age 61.1 ± 4.7 years, height 165.3 ± 5.3 cm; weight 86.9 ± 11.1 kg). The MTI was calculated through the asymmetry index (AI), defined as the sum of the values of asymmetry obtained for each scale from 1 to 10. The AI decreases significantly in healthy subjects from 0.51 ± 0.28 at rest to 0.28 ± 0.24 during exercise (P = 0.01) but not in cardiac patients (−0.2204 ± 0.5097 at rest and 0.0848 ± 0.1200 during exercise; P = 0.07). MTI distinguish adequately the four experimental situations because it can be considered as an index of the internal property of the signal in contrast to linear methods which are highly sensitive to external influences over the heart rhythm, particularly sympathetic and parasympathetic stimuli.
T-wave abnormalities are gaining significance in the realm of electrocardiogram diagnostics. In particular, T-wave alternans are proving to be powerful predictive indicators of potentially fatal arrhythmias. T-wave morphology monitoring and analysis are the means by which alternans and other abnormalities are detected. We have presented a preliminary design of an analog T-wave monitor to provide a characteristic description of the beat-to-beat T-wave morphology in terms of its maximum leading edge and trailing edge slopes, and its area. Experimental results showed that data from the analog T-wave monitor compared well with those predicted theoretically. Current design of the T-wave monitor, once improved, can find use in the screening, diagnosis, and early detection of T-wave abnormalities in clinical settings.
Hemodynamic play a very significant role in the pathophysiology of intracranial arteriovenous malformation. The surgical decisions are based on the understanding of the complexities of the flow. Quantification of the abnormal flow is difficult. The mathematical models provide limited information due to the simplicity of the design of these models. Flow of fluid in a tube is very sensitive to small changes in the diameter. We studied the flow characteristics of a fistula by introducing accurately machined acrylic fistulae between the femoral arteries and veins of dogs. The influences of systemic arterial pressure, diameter of the arterial feeders, volume of blood flow, velocity of flow and the diameter of the shunt on the flow of blood across the shunt were studied. Our experiments suggest that the flow characteristics of an arteriovenous fistulae are complex and are influenced by small changes in the diameters of the fistula and the feeding artery. Our model demonstrates the occurrence of the anomalous flow reduction in the fistula and steal phenomenon and is therefore a more realistic representation of the clinical situation. The design of a mathematical model should include the diameter of the fistula if it is intended to replicate the hemodynamic characteristics of an arteriovenous malformation more faithfully.
Our institution is in development of a low frequency, non-invasive Diastolic Timed Vibrator (DTV) for use in emergency treatment of ST Elevation Myocardial Infarction (STEMI). It is preferable to avoid vibration emissions during the IsoVolumetric Contraction Period (IVCP) and at least the majority of mechanical systole thereafter, as systolic vibration may cause a negative inotropic effect in the ischemic heart. Furthermore diastolic vibration should preferably include the IsoVolumetric Relaxation Period (IVRP) which has been shown in clinical studies to improve cardiac performance and enhance coronary flow. Electrocardiographic (ECG) monitoring can be used to enable diastolic tracking, however, the timing of the phases of the cardiac cycle in relation to the ECG waveform must first be verified. The objective of this study was therefore to determine timing of onset of mechanical systole and diastole in reference to the QRS-T Complex. One hundred and twenty-three adult echocardiographic studies were assessed for the point of mitral and aortic valve closure in relation to the QRS complex and T wave in a representative population. We found that onset of mechanical systole occurred on and usually shortly after the peak of a first dominant QRS complex deflection, and onset of diastole occurred at the earliest on and most commonly beyond the peak or midpoint of the T wave. A DTV should ideally be able to stop vibrating on or before the peak of the first dominant deflection of a QRS complex, and begin vibrating near the peak of the T wave. Given early detection of ventricular depolarization can occur 10–20 ms prior to R wave peak, it is proposed that a DTV should preferably be able to stop vibrating within 10 ms of a triggered stop command. Onset of vibration during peak of T wave could be approximated by a rate adapted Q-T interval regression equation, and then fine tuned by manual adjustment during therapy.
Tortuous or twisted veins are often seen in the retina, cerebrum, and legs (varicose veins) of one-third of the aged population, but the underlying mechanisms are poorly understood. While the collapse of veins under external pressure has been well documented, the bent buckling of long vein segments has not been studied. The objectives of this study were to develop a biomechanical model of vein buckling under internal pressure and to predict the critical pressure. Veins were modeled as thin-walled nonlinear elastic tubes with the Fung exponential strain energy function. Our results demonstrated that veins buckle due to high blood pressure or low axial tension. High axial tension stabilized veins under internal pressure. Our buckling model estimated the critical pressure accurately compared to the experimental measurements. The buckling equation provides a useful tool for studying the development of tortuous veins.
Analysis of digital volume pulse (DVP) signal measured by photoplethysmograph (PPG) technique is a low cost non-invasive method of obtaining vital information related to arterial conditions. In this paper, we present a new two-pulse synthesis (TPS) model for deriving arterial parameters, useful for noninvasive assessment of human vascular health. The model is based on the use of Rayleigh function. Relevance of the proposed model is established by applying it on a sample set of 113 PPG signals, obtained form healthy and treated hypertensive subjects. The TPS model compares well with the conventional methods in determining parameters such as pulse transit time or foot-to-foot delay (D), reflection index (RI), stiffness index (SI) and pulse wave velocity (PWV). A new parameter, viz. differential pulse spread (DPS) has also been introduced for DVP signals using the model. The differential pulse spread provides a new dimension to estimate the process of arterial degeneration.
Our objective was to design, develop, characterize and validate a prototype device for testing the response of aortic valve tissue to impact forces. With each cardiac cycle, the aortic valve, on closure, is subjected to a substantial impact force and the ability of valvular interstitial cells to withstand such forces without apoptosis has not been examined. Our aim was to correlate impact force with apoptosis, identifying the latter using a terminal transferase dUTP nick end-labelling (Tunel) assay. With our drop tower design, we created reproducible impact forces on heart valve tissue resulting in cellular trauma. The reliability of the impact tester design were verified and results showed that normal tissue can withstand impact forces more than 30× greater than the physiological forces to which the tissue is normally exposed. This provides a wide safety margin and indicates that bioengineered aortic valve tissue should have similar properties if it is to withstand physiologic forces long term.
Quantitative evaluation of cardiac function from cardiac magnetic resonance (CMR) images requires the identification of the myocardial walls. This generally requires the clinician to view the image and interactively trace the contours. Especially, detection of myocardial walls of left ventricle is a difficult task in CMR images that are obtained from subjects having serious diseases. An approach to automated outlining the left ventricular contour is proposed. In order to segment the left ventricle, in this paper, a combination of two approaches is suggested. Difference of Gaussian weighting function (DoG) is newly introduced in random walk approach for blood pool (inner contour) extraction. The myocardial wall (outer contour) is segmented out by a modified active contour method that takes blood pool boundary as the initial contour. Promising experimental results in CMR images demonstrate the potentials of our approach.
The conventional impedance cardiogram is a record of pulsatile changes in the electrical impedance of the chest with each heartbeat. The signal seems intuitively related to cardiac stroke volume. However doubts persist about the validity of stroke volume measurements based on electrical impedance. This paper presents a new electrical axis for impedance cardiography that is perpendicular to the conventional head-to-foot axis in an anterior-posterior direction. Dual chest and back electrodes are concentric, permitting tetrapolar technique. A relatively simple analytical model is developed, and this model is validated in a three-dimensional finite element model of current flow through the human chest. Three-dimensional simulations show predictable relationships between the fractional increase in anterior-posterior chest impedance and the ventricular ejection fraction (cardiac stroke volume/ventricular end-diastolic volume). Ejection fraction can be computed accurately with a roughly 30-fold increase in signal level compared to the conventional impedance cardiogram. Breathing causes only modest changes in the signal. When the axis of current flow is optimized, one can interpret the impedance changes during the cardiac cycle with greater confidence as noninvasive, beat-by-beat indicators of ventricular ejection fraction in a wide variety of clinical settings.
