Cardiac Perfusion and Pumping Engineering

The following sections are included:

• REVIEWS

• PREFACE

• CONTENTS

• BOOK SUMMARY

Physiome is considered to be a powerful successor to the genome. Physiome refers to a quantitative description of the physiologic dynamics or functions of the intact organism. It includes integration of knowledge through functional modules and modelling of hierarchic system elements of biologic systems. Biomechanics offers potent tools to promote the physiome concept. By using modern microvisualization technology with physiomic model of coronary circulatory network, this chapter introduces our physiomic approach to coronary microcirculation, which supplies oxygen and nutrients to heart muscles.

The heart is unique, among other organs, in that coronary arterial flow is exclusively diastolic while venous flow is systolic. That is, blood pooled in coronary microvessels (during diastole) is squeezed out to the coronary vein by myocardial contraction. In this chapter, we first describe the biomechanical interaction between coronary blood flow and cardiac contraction. Then, the physiome of coronary capillary network and its functions are discussed.

This chapter concerns with the study of myocardial inhomogeneity in the left ventricular wall. Inhomogeneity is an attribute of both the normal heart and the pathologically compromised heart. In the course of the last couple of decades, this phenomenon has revealed that myocardial inhomogeneity is a modulator of cardiac contractility and/or pump function, although the significance of inhomogeneity for the normal heart has not yet been clarified. Why has nature created such an inhomogeneous device? In this chapter, we seek an answer to this question. We present evidence that the possible role of inhomogeneity in the normal heart is to provide functional reserve for the left ventricle, which is tapped (as needed) to maintain stability of cardiac pumping function throughout the course of life.

Myocardial ischemia occurs when tissue metabolic needs outstrips coronary blood flow or perfusion. The deficiency of the latter is commonly caused by atherosclerotic coronary artery disease, and is diagnosed by various myocardial perfusion imaging techniques that track blood flow heterogeneity between myocardium supplied by normal versus narrowed arteries. Nuclear myocardial perfusion imaging, the most established and ubiquitous of these methods, uses radioactive isotopes (commonly thallium-201-or technetium-99m-based tracer agents) combined with stress and rest imaging protocols, to evaluate regional relative coronary flow reserves, and hence diagnose areas of myocardial ischemia and infarction. Modern image acquisition, using single photon emission computed tomography, allows the reconstruction of a three-dimensional image dataset that facilitates visual analysis as well as quantitation of perfusion. This increases reproducibility of interpretation, and is especially useful in the assessment of myocardial viability. Further, electrocardiographic gating, during the scan acquisition, allows assessment of left ventricular function, which has great prognostic significance. Quantitated perfusion and functional data can be displayed as polar maps that are amenable to comparison with normal databases, thus enhancing the clinical applicability of the technique.

Mathematical modeling provides a useful tool to understand the normal and abnormal mechanical function of the heart. The large deformations that take place during the cardiac cycle require that finite deformation elasticity must be used with the governing laws of physics. In addition, the complex geometry and microstructural arrangement of cardiac muscle requires that numerical and computational methods need to be used to solve the resulting nonlinear equations.

This chapter summarizes a continuum mechanics approach to analyzing myocardial soft tissues, and details how the orthotropic nature of the ventricular myocardium may be efficiently represented. Based on this framework, a finite element analysis of canine ventricles is presented, and the distributions of deformation and regional mechanical stress throughout the heart cycle are quantified.

This chapter essentially provides an overview of LV perfusion and pumping (and connects these two LV functions), by employing different methods for characterizing: (i) pumping in terms of LV passive and active myocardial properties, as well as intra-LV flow velocity and pressure distributions; (ii) perfusion based on detection of LV myocardial ischemic and infarcted segments (by means of echocardiographic texture analysis), SPECT imaging, and computational analysis of intra-myocardial regional perfusion.

Herein, a biomechanical thick-walled cylindrical model of the left ventricle (LV) is developed to demonstrate that the mechanisms of LV internal pressure increase during isovolumic contraction is due to the contraction of the LV myocardial fibers helically wrapped inside the LV wall. The contraction of these fibers deforms and twists the LV. Hence, we can indirectly associate LV twisting with LV contractility. Associated with the LV pressure increase, we have determined the LV (radial, longitudinal, and twist) deformation state. We then determine the LV wall stresses` associated with the deformations, and thereby the principal stresses in the LV wall, along with the axial shortening force and the torque experienced by the LV.

We now hypothesize that the LV principal stresses` orientation corresponds to the orientation of the LV cylindrical model myocardial fibers. This is how we are able to postulate that the contraction of these LV myocardial fibers causes LV deformations, inducing torsion of the LV and associated LV twist angle. Further, the derived orientation of the LV myocardial fibers may be deemed to be an intrinsic property of the LV, and determine its capacity for adequate blood outflow into the aorta.

Left ventricular (LV) filling in turn influences LV contraction because inadequate filling will cause inadequate contraction. Hence, it is important to develop an appropriate LV filling index in terms of monitorable LV pressure and volume. Hence, the prime objective of this chapter is to develop an index to assess the filling functional performance of the LV in terms of monitorable LV pressure and volume.

For this purpose, the LV volume response to the driving pressure term is formulated in terms of a differential equation. This equation is solved for LV volume expression (in terms of the model parameters) for two filling phases: (i) the early filling phase due to LV suction, during which the LV myocardial sarcomere contractile element is relaxing and the driving pressure term (in the governing differential equation) is zero, and (ii) the second phase of filling, due to left atrial contraction.

It may be said that any comparative analysis of contractility indices in the intact heart is somewhat arbitrary, due to lack of an ideal descriptor of the contractile state. Hitherto, left ventricular (LV) (dP/dt)_max has been employed as a measure of LV contractility, and has been shown to be a relatively load-dependent index. It is however an extrinsic measure of LV contractility, because the LV pressure itself is developed by LV wall stress caused by LV myocardial sarcomeric contraction.

It is hence natural to represent LV contractility by means of this intrinsic property of the LV (namely its circumferential wall stress normalized with respect to LV pressure), which is independent of the preload and afterload. For this purpose, our LV spherical model's wall stress is normalized with respect to LV pressure, and its maximum value is adopted as an index of LV contractility.

Our new index is an intrinsic property of the LV, as well as easily and non-invasively obtainable in terms of measurable LV volume and myocardial volume. For the formulation of this contractility index, the LV is modeled as a pressurized thick-walled sphere; to reduce the mathematical complexity and for clinical application convenience. The high degree of correlation between our new and simple contractility index and (dP/dt)_max shows that it is well capable of separating normal LVs from LVs with impaired LV contractility.

It can be said that it is the left ventricular (LV) sarcomere contractility that develops the LV pressure in response to its volume during filling and ejection phases. In this chapter, we develop the governing equations of dynamics of the LV sarcomere contained within the wall of the LV cylindrical model. We then relate the sarcomere stress and displacement to the monitored LV pressure and volume, in terms of the sarcomere elements' parameters (namely the sarcomere contractile element (CE) force and shortening velocity), and evaluate them. We next determine the power generated by the sarcomere (CE) element. All of these indices are deemed to be important LV functional determinants.

The three-dimensional (3D) deformation fields of the LV models were initially estimated from tagged MRI data sets, which provide in-plane temporal correspondence of material points. While there is some initial experience in the use of tagged MRI and related techniques to study the 3D motion of a heart, there is still no generally accepted method for analysis and display of the 3D heart motion. Our parameter-function model captures the 3D deformation field in terms of its model parameters, and the volumetric model can then be regenerated based on the estimated parameters, allowing us to select any desired volume element within the myocardium for a conventional strain analysis.

We have verified that the results of a conventional strain analysis performed on the parameter-function model are in agreement with those from a conventional finite element model. Furthermore, we have proposed a new methodology in visualizing multi-dimensional rendition of the LV overall myocardial strain variation. This will help gain a thorough and localized understanding of the LV motion, and should significantly increase the clinical utility of LV motion analyses.

Coronary artery bypass grafting (CABG) surgery is an effective treatment modality for patients with severe coronary artery disease. CABG is a routine surgical treatment for ischemic heart disease. A large number of CABG cases fail postoperatively due to intimal hyperplasia within months or years, due to deleterious blood-flow velocity and shear–stress distributions at the graft–artery junctions. The conduits used during the surgery include both the arterial and venous conduits. Long-term graft patency rate for the internal mammary arterial graft is superior, but the same is not true for the saphenous vein grafts. At 10 years, more than 50% of the vein grafts would have occluded, and many of them are diseased.

This chapter presents the fluid-dynamics of blood flow in (i) the aorto-right in-plane CABG model (the centerline of the aorta, graft, and the host artery all lie in a plane) and (ii) an out-of-plane CABG model (the centerline of the aorta, graft, and the host artery do not lie in a plane), wherein the left anterior descending artery is bypassed using the sapheneous vein. In our model, the dimensions of the aorta, saphenous vein, and the coronary artery simulate the actual dimensions at surgery, and we employ three-dimensional computational fluid-dynamics, to analyze the blood flow at both proximal and distal anastomoses.

Our results have revealed that (i) maximum perfusion of the occluded artery occurs during mid-diastole, (ii) the maximum wall shear–stress variation is observed around the distal anastomotic region, and (iii) there is a decrease in the magnitude of the peak wall shear–stress at the bed of the anastomosis in the non-planar CABG model as compared to the planar geometry, supporting the view that non-planarity of the blood vessel may lead to better graft patency.

Hemodynamics is widely believed to influence the stenosis of coronary artery bypass graft (CABG). Although distal anastomosis has been extensively investigated, further studies on proximal anastomosis are still necessary, as the extent and initiation of stenosis process may be influenced by the flow at proximal anastomosis per se. Therefore, in this study, firstly, two models (namely 90° and 135° anastomotic models) were designed and constructed to mimic the proximal anastomosis of CABG for left and right coronary arteries, respectively. Flow characteristics of these models were studied by both numerical simulation and particle image velocimetry (PIV) measurement, so as to acquire physical insight of hemodynamics in proximal anastomosis and to validate the simulation result simultaneously. The simulation results showed disturbed flow (such as flow separation, stagnation point, etc.) as well as abnormal hemodynamic parameters (HPs) distributions (including the low and high time-averaged wall shear stress (WSS), oscillation shear index, and time-averaged wall shear stress gradient regions in both the models). In contrast to the 90° model studied, the 135° model is proposed to provide better patency rate, as it has reduced disturbed flow and abnormal HPs.

A fair agreement between numerical and experimental data has been observed in terms of flow characteristics, velocity profiles, and WSS distributions. The discrepancy could be due to the difference in detail geometry of the physical and computational models because of manufacturing limitations to have the exact shape of the computational model when making the Pyrex glass model.

Mechanical blood pumps for temporary or permanent support of cardiac function are classified into the traditional engineering categories of displacement and rotary pumps. Herein, the clinical use and indications of the various pump categories are outlined, and a detailed description of currently available systems is given. The first part deals with extracorporeal as well as implantable ventricular-assist devices (VADs) of the displacement type, and is followed by a section on current developments in the field of total artificial hearts (TAHs). The second part covers rotary blood pumps (RBPs) that are intended as VADs. A brief summary of each RBP system (including specific design aspects of axial, radial, and diagonal pumps) is outlined. This chapter concludes with recommendations on major challenges and future trends in the field of mechanical circulatory support.

This chapter describes some early development efforts on an axial blood pump as a left-ventricle-assist device (LVAD). The performance of the preliminary design model (comprising a flow straightener, inducer/impeller, and a diffuser) is first refined, followed by drive system integration in the prototype. The impeller is first studied in isolation, using numerical flow simulations to improve the impeller geometry in relation to blade thickness, blade angle distribution, wrap angle and hub contour, followed by studies on impeller and diffuser interactions.

The objective is to minimize flow reversal and reduction of scalar stresses in the impeller passage at the designed impeller speed of 10,000 rpm, delivering 5 L/min flow against 100 mmHg pressure. Numerical results predict scalar stresses in the impeller passage near the hub surface to be ranging from 5 × 10⁻⁴ to 8 Pa, while those near the impeller tip region to be ranging from 1 to 150 Pa. The residence time of particles through the impeller is typically less than 0.1 s, suggesting the unlikelihood of hemolysis.

The electric drive is integrated to the pump by incorporating rotor magnets in the inducer–impeller hub and packing stator coils around the pump casing. A brushless rotating field, with feedback from Hall-effect sensors, regulates motor operation. The first prototype has been bench tested, and its results are presented. The pump developed holds promise as a viable LVAD.

This chapter describes the development of a bio-mathematical model used to assess the interaction between an assist device and the native cardiovascular system. First, an overview of mathematical cardiovascular modeling is presented, based on the time-varying elastance concept, an afterload model, and an appropriate assist device model (either a rotary pump or a pneumatic or electromechanical displacement pump). In the second part of the chapter, the mathematical model of the rotary pump is presented, followed by a case study that investigates its unloading capacities of the rotary blood pump in different operating modes.

Cardiovascular Disease (CVD) is one of the world's most prevalent causes of death. Transcending geographical boundaries and population demographics, CVD accounted for 38.5 percent of all deaths or 1 of every 2.6 deaths in the United States in 2001, of which CHD was responsible for more than 1 of every 5 deaths. CHD was thus identified as the single largest killer of Americans (All data resourced from the American Heart Association journal report; 2004 update). There is currently no effective remedy for cardiovascular disease.

There is a compelling need to arrest (if not reverse) the incidence progression of heart disease. Cell transplantation is a promising alternative therapy for myocardial repair. This novel approach seeks to compensate for the extensive loss in cardiomyocytes, which is in turn a consequence of left ventricular dysfunction. The rationale for engrafting cardiomyocytes onto a compromised myocardium is intuitive, and has prompted the initiative for subsequent “proof-of-concept” experimentation. To date, its application in various animal models has been reported with success.

In this chapter, we discuss systematically, novel approaches to cell transplantation, specifically, applications in

(i) myoblast transplantation,

(ii) adult mesenchymal,

(iii) embryonic stem cell engineering, and

(iv) phase I human clinical trials

We also report accomplished milestones in the respective fields of study, and outline the principles underlying each approach. At the same time, we highlight the limitations in each technique, and review current progress in the afore-listed strategies for cell transplantation in the infarcted heart.

Cardiovascular disease is widespread in the developed world, and many suffer from damaged heart tissue resulting in heart failure. Tissue engineering is a field combining the interests of clinicians, molecular scientists, and materials engineers. With the rapid advancement of “materials” science and an understanding of how it interacts with living cells, creating artificial tissues for organ repair seems more of a reality today than ever before. Recent reports on creating spontaneously contracting artificial heart tissue has created excitement, and has spurred on research in this area. This chapter offers a current perspective on strategies employed in engineering artificial heart tissues for reparative therapy of the damaged heart.

The following sections are included:

• INDEX