Papers by Ares Pasipoularides
American Journal of Physiology-heart and Circulatory Physiology, 2003
We describe a novel functional imaging approach for quantitative analysis of right ventricular (R... more We describe a novel functional imaging approach for quantitative analysis of right ventricular (RV) blood flow patterns in specific experimental animals (or humans) using real-time, threedimensional (3-D) echocardiography (RT3D). The method is independent of the digital imaging modality used. It comprises three parts. First, a semiautomated segmentation aided by intraluminal contrast medium locates the RV endocardial surface. Second, a geometric scheme for dynamic RV chamber reconstruction applies a time interpolation procedure to the RT3D data to quantify wall geometry and motion at 400 Hz. A volumetric prism method validated the dynamic geometric reconstruction against simultaneous sonomicrometric canine measurements. Finally, the RV endocardial border motion information is used for mesh generation on a computational fluid dynamics solver to simulate development of the early RV diastolic inflow field. Boundary conditions (tessellated endocardial surface nodal velocities) for the solver are directly derived from the endocardial geometry and motion information. The new functional imaging approach may yield important kinematic information on the distribution of instantaneous velocities in the RV diastolic flow field of specific normal or diseased hearts.
American Journal of Physiology-heart and Circulatory Physiology, Apr 1, 2003
Functional imaging computational fluid dynamics simulations of right ventricular (RV) inflow fiel... more Functional imaging computational fluid dynamics simulations of right ventricular (RV) inflow fields were obtained by comprehensive software using individual animal-specific dynamic imaging data input from three-dimensional (3-D) real-time echocardiography (RT3D) on a CRAY T-90 supercomputer. Chronically instrumented, lightly sedated awake dogs (n = 7) with normal wall motion (NWM) at control and normal or diastolic paradoxical septal motion (PSM) during RV volume overload were investigated. Up to the E-wave peak, instantaneous inflow streamlines extended from the tricuspid orifice to the RV endocardial surface in an expanding fanlike pattern. During the descending limb of the E-wave, large-scale (macroscopic or global) vortical motions ensued within the filling RV chamber. Both at control and during RV volume overload (with or without PSM), blood streams rolled up from regions near the walls toward the base. The extent and strength of the ring vortex surrounding the main stream were reduced with chamber dilatation. A hypothesis is proposed for a facilitatory role of the diastolic vortex for ventricular filling. The filling vortex supports filling by shunting inflow kinetic energy, which would otherwise contribute to an inflow-impeding convective pressure rise between inflow orifice and the large endocardial surface of the expanding chamber, into the rotational kinetic energy of the vortical motion that is destined to be dissipated as heat. The basic information presented should improve application and interpretation of noninvasive (Doppler color flow mapping, velocity-encoded cine magnetic resonance imaging, etc.) diastolic diagnostic studies and lead to improved understanding and recognition of subtle, flow-associated abnormalities in ventricular dilatation and remodeling.
Journal of Applied Physiology, Jun 1, 2013
In Harvey's Exercitatio Anatomica de Motu Cordis et Sanguinis in Animalibus of 1628, we see the m... more In Harvey's Exercitatio Anatomica de Motu Cordis et Sanguinis in Animalibus of 1628, we see the mechanisms of the Circulation worked out more or less in full from the results of experimental demonstration, virtually complete but for the direct visual evidence of a link between the minute final terminations and initial branches of the arterial and venous systems, respectively. This would become available only when the capillaries could be seen under the microscope, by Malpighi. Harvey's amazingly modern order of magnitude analysis of volumetric circulatory flow and appreciation of the principle of continuity (mass conservation), his adroit investigational uses of ligatures of varying tightness in elegant flow experiments, and his insightful deductions truly explain the movement of the blood in animals. His end was accomplished. So radical was his discovery that early in the 18th century, the illustrious Hermann Boerhaave, professor of medicine at Leyden, declared that nothing that had been written before Harvey was worthy of consideration any more. The conclusions of De Motu Cordis are unassailable and beautiful in their simplicity. Harvey's genius and tireless determination have served physiology and medicine well. Aristotle and circular motions; Galen's De Usu Partium; William Harvey's De Motu Cordis; William Harvey's order of magnitude analysis of volumetric circulatory flow; blood circulation All truths are easy to understand once they are discovered; the point is to discover them-attributed to Galileo Galilei THE CIRCULATION OF BLOOD AND the physiologic function of the heart as a pump were established by the English physicianphysiologist William Harvey (1578-1657) (44), who is considered to be the father of modern experimental physiology. Harvey studied medicine at Padua (now Padova), near Venice, which at the time had the most prestigious medical university in Europe. It was also one of the most Aristotelian, but Paduan Aristotelianism differed from the genre taught elsewhere: at Padua, they taught Aristotle as a preliminary to medicine, not theology (44). Since the early 15th century, Padua had been ruled by Venice, which fostered freedom of thought. At Padua, Harvey was a pupil of Casserius and, most notably, of the great anatomist Hieronymus Fabricius of Aquapendente who, after Aristotle (60), became known as a father of embryology (28). Besides Harvey, the intellectual climate attracted many of the ablest minds of the time-among them Vesalius, Copernicus, and Galileo (7, 51).
International Journal of Cardiology, Feb 1, 2014
Leonardo, polymath disciple of experience Aristotelian cause-and-effect analysis Leonardo's human... more Leonardo, polymath disciple of experience Aristotelian cause-and-effect analysis Leonardo's human anatomical charts Leonardo's 4-chambered heart Leonardo's identification of the coronary vessels Leonardo's cardiac vortices and their role in valve closure Leonardo da Vinci, the first modern scientist Early modern medical science did not arise ex nihilo, but was the culmination of a long history stretching back through the Renaissance, the Middle Ages, Byzantium and Roman times, into Greek Antiquity. The long interval between Aristotle and Galen and Harvey and Descartes was punctuated by outstanding visionaries, including Leonardo, the ultimate Renaissance man. His attitude and mindset were based on Aristotelian pursuit of empirical fact and rational thought. He declared himself to be a "man without letters" to underscore his disdain for those whose culture was only mnemonics and philosophical inferences from authoritative books. Leonardo read the Book of Nature with the immense curiosity of the pioneering scientist, ushering in the methodology of modern medical science with help from forerunners. He left no publications, but extensive personal Notebooks: on his scientific research, hydrodynamics, physiological anatomy, etc. Apparently, numerous successors availed themselves of his methodologies and insights, albeit without attribution. In his Notebooks, disordered and fragmentary, Leonardo manifests the exactitude of the engineer and scientist, the spontaneous freshness of one speaking of what he has at heart and that he knows well. His style is unrefined, but intensely personal, rich with emotion and, sometimes, poetic. Leonardo, the visionary anatomist, strived consistently not merely to imitate nature by depicting body structures, but to perceive through analysis and simulations the intimate physiologic processes; i.e., the biomechanics underlying the workings of all bodily organs and components, even the mysterious beating heart. It is fitting to regard him as the first modern medical scientist.
Journal of Molecular and Cellular Cardiology, Feb 1, 2018
Genomics designates the coordinated investigation of a large number of genes in the context of a ... more Genomics designates the coordinated investigation of a large number of genes in the context of a biological process or disease. It may be long before we attain comprehensive understanding of the genomics of common complex cardiovascular diseases (CVDs) such as inherited cardiomyopathies, valvular diseases, primary arrhythmogenic conditions, congenital heart syndromes, hypercholesterolemia and atherosclerotic heart disease, hypertensive syndromes, and heart failure with preserved/reduced ejection fraction. Nonetheless, as genomics is evolving rapidly, it is constructive to survey now pertinent concepts and breakthroughs. Today, clinical multimodal electronic medical/health records (EMRs/EHRs) incorporating genomic information establish a continuously-learning, vast knowledge-network with seamless cycling between clinical application and research. It can inform insights into specific pathogenetic pathways, guide biomarker-assisted precise diagnoses and individualized treatments, and stratify prognoses. Complex CVDs blend multiple interacting genomic variants, epigenetics, and environmental riskfactors, engendering progressions of multifaceted disease-manifestations, including clinical symptoms and signs. There is no straight-line linkage between genetic cause(s) or causal genevariant(s) and disease phenotype(s). Because of interactions involving modifier-gene influences, (micro)-environmental, and epigenetic effects, the same variant may actually produce dissimilar abnormalities in different individuals. Implementing genome-driven personalized cardiology in clinical practice reveals that the study of CVDs at the level of molecules and cells can yield crucial clinical benefits.
International Journal of Cardiology, Mar 1, 2017
For most of Medicine's past, the best that physicians could do to cope with disease prevention an... more For most of Medicine's past, the best that physicians could do to cope with disease prevention and treatment was based on the expected response of an average patient. Currently, however, a more personalized/precise approach to cardiology and medicine in general is becoming possible, as the cost of sequencing a human genome has declined substantially. As a result, we are witnessing an era of precipitous advances in biomedicine and bourgeoning understanding of the genetic basis of cardiovascular and other diseases, reminiscent of the resurgence of innovations in physico-mathematical sciences and biology-anatomy-cardiology in the Renaissance, a parallel time of radical change and reformation of medical knowledge, education and practice. Now on the horizon is an individualized, diverse patient-centered, approach to medical practice that encompasses the development of new, gene-based diagnostics and preventive medicine tactics, and offers the broadest range of personalized therapies based on pharmacogenetics. Over time, translation of genomic and high-tech approaches unquestionably will transform clinical practice in cardiology and medicine as a whole, with the adoption of new personalized medicine approaches and procedures. Clearly, future prospects far outweigh present accomplishments, which are best viewed as a promising start. It is now essential for pluridisciplinary health care providers to examine the drivers and barriers to the clinical adoption of this emerging revolutionary paradigm, in order to expedite the realization of its potential. So, we are not there yet, but we are definitely on our way.
Journal of Cardiovascular Translational Research, May 16, 2016
In part 1, we considered cytomolecular mechanisms underlying calcific aortic valve disease (CAVD)... more In part 1, we considered cytomolecular mechanisms underlying calcific aortic valve disease (CAVD), hemodynamics, and adaptive feedbacks controlling pathological left ventricular hypertrophy provoked by ensuing aortic valvular stenosis (AVS). In part 2, we survey diverse signal transduction pathways that precede cellular/molecular mechanisms controlling hypertrophic gene expression by activation of specific transcription factors that induce sarcomere replication inparallel. Such signaling pathways represent potential targets for therapeutic intervention and prevention of decompensation/failure. Hypertrophy provoking signals, in the form of dynamic stresses and ligand/effector molecules that bind to specific receptors to initiate the hypertrophy, are transcribed across the sarcolemma by several second messengers. They comprise intricate feedback mechanisms involving gene network cascades, specific signaling molecules encompassing G protein-coupled receptors and mechanotransducers, and myocardial stresses. Future multidisciplinary studies will characterize the adaptive/maladaptive nature of the AVSinduced hypertrophy, its gender-and individual patient-dependent peculiarities, and its response to surgical/medical interventions. They will herald more effective, precision medicine treatments.
American Heart Journal, 2007
In this issue of the Journal, Nemes et al 1 consider alterations in aortic stiffness during a 1ye... more In this issue of the Journal, Nemes et al 1 consider alterations in aortic stiffness during a 1year follow-up after aortic valve replacement (AVR). Twelve patients with severe aortic stenosis (AS) who underwent AVR were prospectively investigated. As expected, stenosis severity and left ventricular (LV) mass decreased significantly after AVR. Moreover, aortic luminal diameter changes (systolic minus diastolic dimensions) progressively increased and aortic stiffness decreased to levels comparable to those of age-, gender-, and risk factormatched controls at 1 year. Some readers might find it counterintuitive that the pulse pressure in uncorrected severe AS tended to be greater than at 12 months after AVR. Rethinking the apparently simple but actually complex is central to understanding the interacting hemodynamic changes beneath this seemingly paradoxical finding. We start with an integrative overview of ventricular loading. The ventricular systolic ejection load represents pressure against which the walls contract and is to be distinguished from myocardial loading or wall stress, to which it is related by complex cardiomorphometric and histoarchitectonic factors. The total ventricular systolic load, or afterload, determines the manner by which the mechanical energy generated by the actin-myosin interactions in the ventricular walls is converted to the work that pumps blood through the circulation. Under any given contractile state, increased afterload reduces ejection rate and stroke volume. Conversely, when afterload decreases, a larger volume is ejected at higher ejection velocities. 2-5 These changes result from the inverse force-velocity relation of the working myocardium. 3,4 Extrinsic component of the total ventricular systolic load It is the interaction of the ejection flow patterns generated by the left (right) ventricle at the aortic (pulmonic) root with the systemic (pulmonary) input impedance 6,7 that gives rise to the extrinsic component of the total ventricular systolic load. This view differs from the widely quoted formulation, by Milnor, 8 of the arterial impedance as the complete representation of the ventricular afterload. First, Milnor's formulation neglects entirely the intrinsic component of systolic ventricular loading (ie, the intraventricular flow-associated
Annals of Biomedical Engineering, 1992
This survey of cardiac hemodynamics updates evolving concepts of myocardial and ventricular systo... more This survey of cardiac hemodynamics updates evolving concepts of myocardial and ventricular systolic and diastolic loading and function. The pumping action of the heart and its interactions with arterial and venous systems in health and disease provide an extremely rich and challenging field of research, viewed from a fluid dynamic perspective. Many of the more important problems in this field, even if the fluid dynamics in them are considered in isolation, are found to raise questions which have not been asked in the history o f fluid dynamics research. Biomedical engineering will increasingly contribute to their solution.
Journal of Cardiovascular Translational Research, Jan 27, 2015
Epigenetic mechanisms are fundamental in cardiac adaptations, remodeling, reverse remodeling, and... more Epigenetic mechanisms are fundamental in cardiac adaptations, remodeling, reverse remodeling, and disease. This 2-article series proposes that variable forces associated with diastolic RV/LV rotatory intraventricular flows can exert physiologically and clinically important, albeit still unappreciated, epigenetic actions influencing functional and morphological cardiac adaptations and/or maladaptations. Taken in-toto, the 2-part survey formulates a new paradigm in which intraventricular diastolic filling vortex-associated forces play a fundamental epigenetic role, and examines how heart cells react to these forces. The objective is to provide a perspective on vortical epigenetic effects, to introduce emerging ideas and suggest directions of multidisciplinary translational research. The main goal is to make pertinent biophysics and cytomechanical dynamic systems concepts accessible to interested translational and clinical cardiologists. I recognize that the diversity of the epigenetic problems can give rise to a diversity of approaches and multifaceted specialized research undertakings. Specificity may dominate the picture. However, I take a contrasting approach. Are there concepts that are central enough that they should be developed in some detail? Broadness competes with specificity. Would however this viewpoint allow for a more encompassing view that may otherwise be lost by generation of fragmented results? Part 1 serves as a general introduction, focusing on background concepts, on intracardiac vortex imaging methods, and on diastolic filling vortex-associated forces acting epigenetically on RV/LV endocardium and myocardium. Part 2 will describe pertinent available pluridisciplinary knowledge/research relating to mechanotransduction mechanisms for intraventricular diastolic vortex forces and myocardial deformations and to their epigenetic actions on myocardial and ventricular function and adaptations.
Journal of Cardiovascular Translational Research, Nov 21, 2012
Ventricular compliance alterations can affect cardiac performance and adaptations. Moreover, dias... more Ventricular compliance alterations can affect cardiac performance and adaptations. Moreover, diastolic mechanics are important in assessing both diastolic and systolic function, since any filling impairment can compromise systolic function. A sigmoidal passive filling pressure-volume relationship, developed using chronically instrumented, awake-animal disease models, is clinically adaptable to evaluating diastolic dynamics using subject-specific micromanometric and volumetric data from the entire filling period of any heartbeat(s). This innovative relationship is the global, integrated expression of chamber geometry, wall thickness, and passive myocardial wall properties. Chamber and myocardial compliance curves of both ventricles can be computed by the sigmoidal methodology over the entire filling period and plotted over appropriate filling pressure ranges. Important characteristics of the compliance curves can be examined and compared between the right and the left ventricle, and for different physiological and pathological conditions. The sigmoidal paradigm is more accurate and, therefore, a better alternative to the conventional exponential pressure-volume approximation.
American Heart Journal, Nov 1, 2011
Conventional and emerging concepts on mechanisms by which hypertrophic cardiomyopathy (HCM) engen... more Conventional and emerging concepts on mechanisms by which hypertrophic cardiomyopathy (HCM) engenders diastolic dysfunction are surveyed. A shift from familiar left ventricular (LV) diastolic function approaches to large-scale (twist-untwist) and small-scale (titin unfoldingrefolding, etc.) wall rebound models, incorporating interaction and dynamic distortions and rearrangements of myofiber sheets and ultrastructural constituents, is suggested. Such an emerging new paradigm of diastolic dynamics, emphasizing the relationship of myofiber sheet and ultraconstituent distortion to LV mechanics and end-systolic shape, might clarify intricate patterns of early diastolic rebound and suction, needed for LV filling in many of the polymorphic phenotypes of HCM. Janus was a Roman deity with 2 faces (Janus bifrons), looking backward and forward simultaneously just as gates look in both directions (Figure 1). He too watched entrances and exits, and his shrines were located at crossing places or intersections. The left ventricle as Janus bifrons The pumping left ventricle forms the intersection or central link (Figure 1) between the lowpressure and the high-pressure systems of the circulatory ensemble. 1 It is a suctioncompression positive-displacement pump, exhibiting both self-regulating properties as an independent organ and dependent properties as part of the overall circulation. In diastole, it adapts to the low-pressure system from which it draws blood, whereas, in systole, it adjusts to the high-pressure system into which it must force blood. For that reason, it needs to alternate between the widely disparate functional-structural requirements of systole and diastole. 1 Since like Janus it can look directly backward and forward, into the low-and high-pressure systems, it displays remarkable Janus-like characteristics. Hence, it subserves at times incongruous functions, such as when excessive wall hypertrophy in response to a systolic pressure overload is associated with diminished diastolic distending wall stress levels and, not uncommonly, with increased muscle stiffness, both of which may then be responsible for impaired left ventricular (LV) diastolic filling. 2-4 Almost all forms of heart disease and most strikingly hypertrophic cardiomyopathy (HCM) alter ventricular structure. The changes in
The Journal of Thoracic and Cardiovascular Surgery, Nov 1, 2002
Glower and Pasipoularides Objective: Limitations in clinical understanding of right ventricular r... more Glower and Pasipoularides Objective: Limitations in clinical understanding of right ventricular relaxation can be attributed to the paucity of information from basic studies in animal models of right ventricular disease. This study examined, in the conscious state, right ventricular relaxation dynamics under normal conditions (n ϭ 15) and in subacute (2-5 weeks) canine models of right ventricular pressure overload (n ϭ 6), volume overload (n ϭ 7), and free wall ischemia (n ϭ 7). Methods: Right-heart micromanometric measurements were obtained by using multisensor catheters. A new algorithm was developed to obtain representative ensemble averages of hemodynamic waveform data sets. Right ventricular relaxation was analyzed by using an exponential model with 3 parameters: P 0 , , and P b. Significant changes versus control values were determined by means of analysis of variance and the Student unpaired t test with Bonferroni's adjustment. Results: In the state of pressure overload, right ventricular pressure decay exhibits an increased P 0 (56.2 Ϯ 19.1 vs 13.1 Ϯ 5.1 mm Hg [mean Ϯ SD]) and prolonged (57.1 Ϯ 2.8 vs 27.8 Ϯ 3.9 ms); there is also a decreased P b (Ϫ7.9 Ϯ 1.5 vs 0.28 Ϯ 1.8 mm Hg). The only significant change in volume overload is an increased asymptote, P b (5.3 Ϯ 2.9 mm Hg). In right ventricular ischemia, prolongation of (41.4 Ϯ 13.0 ms) and decreased P b (Ϫ1.95 Ϯ 1.1 mm Hg) attain high significance. Conclusions: Distinctive abnormalities in right ventricular relaxation dynamics accompany pressure overload, volume overload, and ischemia and may contribute to clinical right ventricular dysfunction. R ight ventricular (RV) dysfunction is implicated in nearly 20% of all deaths associated with congestive heart failure, 1-4 and the right ventricle plays a crucial role in the cardiopulmonary interactions of many disease states. 1,2 Moreover, RV dysfunction is often the limiting factor for the success of coronary bypass surgery, heart transplantation, or heart-lung transplantation. 5,6 Despite its physiologic and clinical importance, however, little attention has been paid to relaxation abnormalities, specifically those of the right ventricle. 1-4,6 Limitations of our understanding can be attributed to the paucity of information from basic studies of RV relaxation in appropriate animal disease models. The aim of the present study was to study RV relaxation dynamics in subacute animal models of RV pressure overload, RV volume overload, and RV free wall ischemia.
Journal of Cardiovascular Translational Research, Apr 13, 2013
A conceptual fluid-dynamics framework for diastolic filling is developed. The convective decelera... more A conceptual fluid-dynamics framework for diastolic filling is developed. The convective deceleration load (CDL) is identified as an important determinant of ventricular inflow during the E-wave (A-wave) upstroke. Convective deceleration occurs as blood moves from the inflow anulus through larger-area cross-sections toward the expanding walls. Chamber dilatation underlies previously unrecognized alterations in intraventricular flow dynamics. The larger the chamber, the larger become the endocardial surface and the CDL. CDL magnitude affects strongly the attainable E-wave (A-wave) peak. This underlies the concept of diastolic ventriculoannular disproportion. Large vortices, whose strength decreases with chamber dilatation, ensue after the Ewave peak and impound inflow kinetic energy, averting an inflow-impeding, convective Bernoulli pressure-rise. This reduces the CDL by a variable extent depending on vortical intensity. Accordingly, the filling vortex facilitates filling to varying degrees, depending on chamber volume. The new framework provides stimulus for functional genomics research, aimed at new insights into ventricular remodeling. Keywords diastolic filling vortex; ventricular chamber volumes; diastolic function; heart failure; ventricular remodeling; convective deceleration load; diastolic ventriculoannular disproportion; functional genomics of intracardiac blood flow "Cardiology is flow." Richter Y. & Edelman E.R. (2006). Circulation 113, 2679. Diastolic cardiac dysfunction as a component of heart failure is nowadays sufficiently recognized as to be a part of coding for congestive heart failure (CHF) in the International Classification of Diseases (ICD-10, codes I50.30-33). This WHO recognition of diastole has been accompanied by major strides in the appraisal of diastolic function [1-4], made possible by technology encompassing multisensor cardiac catheterization [1,2,5,6] and new digital imaging modalities [1,6-8]. It is now widely appreciated that enhancing diastolic filling has clinical merit and that the significance of diastolic dysfunction is far reaching [9]. Nonetheless, the fact that in health and disease diastolic dynamics are dependent on a large number of factors and their interactions [1,10] has complicated evaluation of the multifactorial causes of the observed ventricular filling abnormalities.
Circulation Research, Feb 1, 1991
The effects of developing perinephritic hypertension (2-3 weeks) and a more stable period of peri... more The effects of developing perinephritic hypertension (2-3 weeks) and a more stable period of perinephritic hypertension (-14 weeks) were examined on indexes of left ventricular (LV) diastolic function in conscious, chronically instrumented dogs. The complete period of diastole was studied using indexes of isovolumic relaxation (T-), early filling (LV +dD/dt), and stiffness (myocardial stiffness and chamber stress/diameter ratio). During developing hypertension, increased LV end-diastolic pressure, LV end-diastolic stress, peak filling rate, myocardial stiffness, and the stress/diameter ratio increased (p<0.05); the time constant x was not changed. These changes were associated with preserved baseline levels of coronary blood flow (radioactive microspheres) but an impaired coronary vasodilator response to adenosine. Acute administration of phenylephrine in the normotensive dogs caused increases in systolic and diastolic stress and resulted in increases in myocardial stiffness and in the stress/diameter ratio similar to values observed in developing hypertension. During stable hypertension, LV end-diastolic stress, peak filling rate, and both parameters of late-diastolic function (myocardial stiffness and stress/diameter ratio) returned toward control values, but the isovolumic relaxation time constant was increased. Quantitative histological evaluation revealed no increase in stainable connective tissue in dogs with stable hypertension compared with control dogs, and hydroxyproline concentration was not increased in the subendomyocardium, midmyocardium, or subepimyocardium of the dogs with chronic perinephritic hypertension. Thus, in developing hypertension, major alterations in diastolic function were observed that were not structurally related, since these changes 1) could be induced in normal dogs by increasing preload and afterload acutely with phenylephrine and 2) were improved during the ensuing stable period of hypertension.
Journal of the American College of Cardiology, 1991
Circulation Research, Aug 1, 1987
Simultaneous intraventricular pressure gradients and ejection flow patterns were measured by a mu... more Simultaneous intraventricular pressure gradients and ejection flow patterns were measured by a multisensor catheter in 6 patients with normal left ventricular function and no valve abnormalities, at rest and in exercise. Peak measured intraventricular pressure gradients were attained very early in ejection, amounted to 6.7 ± 1.9 (SD) mm Hg at rest, and were intensified to 13.0 ± 2.3 mm Hg during submaximal supine bicycle exercise. The augmentation of the gradients during exercise was associated with a pronounced accentuation of the flow acceleration and flow at the instant of peak gradient. At peak flow, the intraventricular gradients amounted to 5.4± 1.7 mm Hg at rest and 10.0±1.8 mm Hg during submaximal exercise. The exercise-induced enhancement of the measured intraventricular pressure difference at the time of peak flow was underlain by an accentuation of the peak flow itself. A semiempirical fluid dynamic model for ejection was applied to the pressure gradient and simultaneous outflow rate and acceleration data to identify the contributions by local and convective acceleration effects to the instantaneous intraventricular gradient values. The peak intraventricular pressure gradient, which is attained very early in ejection, is mostly accounted for by local acceleration effects (85 ±5% of the total). Conversely, at peak flow only convective acceleration effects are responsible for the measured pressure gradient. Thus, when inertia! effects are augmented, as in exercise and other hyperdynamic states, the intrinsic component of the total left ventricular systolic load can be substantial, even with no outflow tract or valve abnormalities. In view of the inverse force-velocity relation of the myocardium, this implies that the intrinsic component of the left ventricular load and the corresponding component of the left ventricular muscle load must be taken into account in exploring analytically the loading feedback between the total myocardial load and the acceleration, velocity and extent of shortening, which, along with end-diastolic dimensions, determine ejection flow waveforms.
Circulation, Nov 1, 1986
We have developed a model for assessing the influence of the decaying contractile systolic tensio... more We have developed a model for assessing the influence of the decaying contractile systolic tension on diastolic wall dynamics and the passive properties of left ventricular muscle. Total measured left ventricular diastolic pressure and stress (aT) are determined by two overlapping processes: (1) the decay of actively developed pressure and stress (5A) and (2) the buildup of passive filling pressure and stress (C*). The decaying contractile stress aA iS formulated in terms of a relaxation pressure with a time constant (T) assessed during the isovolumic relaxation interval. By subtracting the contribution of aA from aT we obtain 0*. With micromanometry, echocardiography,and cineangiography, total and passive stress-strain relations and strain rates were evaluated over the entire filling period in six normal control subjects and in seven patients with aortic stenosis. Elastic stiffness constants (k), the slopes of the linear passive stiffness vs 0* relations, did not differ in the two groups over a common lower stress range (6/6 normal, k = 9.37 + 1.23; 7/7 aortic stenosis, k = 9.34 + 1.08). Over a higher 0* range, transition into a much steeper linear region occurred, and k values were much larger (4/7 aortic stenosis, k = 28.76 + 2.02). When diastolic stress levels are elevated, passive stiffness-stress relations can be better described as bilinear, with a much greater wall stiffness constant in the higher than in the lower stress range. Dynamic effects of decaying systolic contractile wall stress components are important in the rapid filling phase in normal hearts as well as in those with aortic stenosis. Circulation 74, No. 5, 991-1001, 1986. ANIMAL and clinical investigations have demonstrated that diastolic pressure-volume relations can be altered either by acute interventions, such as hypoxia and ischemia, or by chronic disease states such as pressure overload. 1-3 Mathematical analyses-6 have shown that the effects of changes in chamber geometry and wall mass have to be distinguished from those of changes in the elastic properties of the cardiac muscle itself. In such analytical models it is assumed that the ventricular wall acts as a passive medium and the models can be applied to the beating ventricle only in the latter part of diastole, a time when contractile stresses have decayed to negligible levels. In early diastole, after mitral valve opening, left ventricular pressure continues to fall, although the chamber is expanding.7' The early diastolic deviation from what is ex-From the
Progress in Cardiovascular Diseases, 1990
Computer software for the IBM PC was developed to assess the contractile properties of the right ... more Computer software for the IBM PC was developed to assess the contractile properties of the right and left ventricles simultaneously. Four indices of systolic function were computed from pressure and volume data. These four indices consist of the slopes and x intercepts of lines fitted to different aspects of the pressure-volume relationship. A shell-subtraction model was utilized to compute the
Uploads
Papers by Ares Pasipoularides