A. Jung, N. Kayhan, G. Reinerth, O. Dössel, and C. F. Vahl. Mechanisch induzierte Dissoziation von Kalzium vom kontraktilen Apparat elektrisch stimulierter, intakter, menschlicher, atrialer Trabekel. In Zeitschrift für Herz-, Thorax- und Gefäßchirurgie, vol. 18(5) , pp. 246-253, 2004
Die kurzzeitige Kalzium-Akkumulation im myokardialen Gewebe bei isotoner Kontraktion ist von klinischer Bedeutung, da die Kalziumüberladung des Zytosols ursächlich an der Entstehung von Rhythmusstörungen beteiligt ist. Unklar ist derzeit, woher das überschüssige Kalzium stammt, ob aus intrazellulären Speichern, modifizierten Membranströmen oder von Seiten des kontraktilen Apparates. Ziel dieser Arbeit ist es zu klären, 1) an welcher Stelle in der Zelle das Kalzium freigesetzt wird und 2) ob das Ausmaß der Aktin-Myosin- Überlappung oder die Anzahl angelagerter Querbrücken die Pufferkapazität des kontraktilen Apparates für Kalzium mitbestimmen.Methoden Muskeltrabekel von 18 Patienten, die sich einer Herzoperation unterzogen, wurden untersucht. Während isometrischer Kontraktion der Präparate setzte kurzzeitige, sinusoidale Längenvibration (Frequenz: 125 Hz, Amplitude: 14% ML) ein. Besonderes Augenmerk lag hierbei auf der Reaktion des Kalzium-Signals (Indikator: Fura-2/AM). In einer zweiten Messreihe wurde dieser Versuch nach Zugabe von 10 mM BDM wiederholt, das bekannt ist für seine Kraftminderung durch Senkung der Kalzium-Sensitivität des Troponin C. Im dritten Versuchsblock wurde permanente Vibration angewandt.Ergebnisse 1) Induzierte Vibration reduzierte die aktive Kraft auf das Niveau der Ruhekraft. Zeitgleich kam es zu einer messbaren Zunahme des Kalziums im Zytosol. 2) Bei subtotaler Inhibition der elektromechanischen Kopplung durch BDM erreichte die aktive Kraft 10,4% der Kontrolle bei nahezu unverändertem Kalziumsignal (Kalzium-Zeit-Integral unter BDM: 91,9±3,2% der Kontrolle). Vibration führte unter diesen Bedingungen zu einer Kraftinhibition, ohne dass eine zusätzliche Kalzium-Freisetzung erreicht wurde. 3) Permanente Vibration reduzierte die Kraftamplitude des supramaximal aktivierten Präparates auf 28% (1,3±0,4 mN). Gleichzeitig stieg das Kalzium-Zeit-Integral auf 114,5±4,7%.Schlussfolgerung Die Befunde sprechen dafür, dass die Reduktion der Anzahl angelagerter Querbrücken beim Verkürzungsvorgang zu einer Verminderung der Empfindlichkeit des kontraktilen Apparates für Kalzium führt. Die verminderte Pufferkapazität des kontraktilen Apparates für Kalzium wird messbar durch eine Zunahme der Kalziumkonzentration im Zytosol, wenn bereits angelagerte Querbrücken durch Vibration mechanisch gelöst werden oder wenn die Anlagerung von Querbrücken durch permanente Vibration verhindert wird. Dieser Befund erklärt die klinische Beobachtung, dass die akute Nachlastsenkung häufig mit dem Auftreten von Rhythmusstörungen verbunden ist.
L. M. Popp, G. Seemann, and O. Dössel. A simulation study of the reaction of human heart to biphasic electrical shocks. In BMC Cardiovascular Disorders, vol. 4, pp. 9, 2004
BACKGROUND: This article presents a study, which examines the effects of biphasic electrical shocks on human ventricular tissue. The effects of this type of shock are not yet fully understood. Animal experiments showed the superiority of biphasic shocks over monophasic ones in defibrillation. A mathematical computer simulation can increase the knowledge of human heart behavior. METHODS: The research presented in this article was done with different models representing a three-dimensional wedge of ventricular myocardium. The electrophysiology was described with Priebe-Beuckelmann model. The realistic fiber twist, which is specific to human myocardium was included. Planar electrodes were placed at the ends of the longest side of the virtual cardiac wedge, in a bath medium. They were sources of electrical shocks, which varied in magnitude from 0.1 to 5 V. In a second arrangement ring electrodes were placed directly on myocardium for getting a better view on secondary electrical sources. The electrical reaction of the tissue was generated with a bidomain model. RESULTS: The reaction of the tissue to the electrical shock was specific to the initial imposed characteristics. Depolarization appeared in the first 5 ms in different locations. A further study of the cardiac tissue behavior revealed, which features influence the response of the considered muscle. It was shown that the time needed by the tissue to be totally depolarized is much shorter when a biphasic shock is applied. Each simulation ended only after complete repolarization was achieved. This created the possibility of gathering information from all states corresponding to one cycle of the cardiac rhythm. CONCLUSIONS: The differences between the reaction of the homogeneous tissue and a tissue, which contains cleavage planes, reveals important aspects of superiority of biphasic pulses.
A shortcoming of current coronary MRA methods with thin-slab 3D acquisitions is the time-consuming examination necessitated by extensive scout scanning and precise slice planning. To improve ease of use and cover larger parts of the anatomy, it appears desirable to image the entire heart with high spatial resolution instead. For this purpose, an isotropic 3D-radial acquisition was employed in this study. This method allows undersampling of k-space in all three spatial dimensions, and its insensitivity to motion enables extended acquisitions per cardiac cycle. We present initial phantom and in vivo results obtained in volunteers that demonstrate large volume coverage with high isotropic spatial resolution. We were able to visualize all major parts of the coronary arteries retrospectively from the volume data set without compromising the image quality. The scan time ranged from 10 to 14 min during free breathing at a heart rate of 60 bpm, which is comparable to that of a thin-slab protocol comprising multiple scans for each coronary artery.
F. B. Sachse. Computational cardiology : modelling of anatomy, electrophysiology, and mechanics. Springer, Heidelberg. 2004.
Electrical activity in biological media can be described in a mathematical way, which is applicable to computer-based simulation. Biophysically mathematical descriptions provide important insights into the electrical and electrophysiological properties of cells, tissues, and organs. Examples of these descriptions are Maxwell's and Poisson's equations for electromagnetic and electric fields. Commonly, numerical techniques are applied to calculate electrical fields, e.g. the finite element method. Finite elements can be classified on the order of the underlying Interpolation. High-order finite elements provide enhanced geometric flexibility and can increase the accuracy of a solution. The aim of this work is the design of a framework for describing and solving high-order finite elements in the SCIRun/BioPSE software system, which allows geometric modeling, simulation, and visualization for solving bioelectric field problems. Currently, only low-order elements are supported. Our design for high-order elements concerns interpolation of geometry and physical fields. The design is illustrated by an implementation of one-dimensional elements with cubic interpolation of geometry and field variables.
M. A. Golombeck, and O. Dössel. MR-tomography on patients with heart pacemakers-a numerical study. In Conference Proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference, vol. 2, pp. 1076-1079, 2004
Patients having a heart pacemaker are not allowed to go to MR tomography (MRT). One of the most dangerous effects is the heating of the tissue around the electrode caused by the coupling to the RF field of the MR system. Experiments have been carried out using tanks filled with saline water and large heating has sometimes been observed. Other experiments e.g. with electrodes in the brain did not show any heating at all. In this work numerical studies have been carried out to understand the different results. In conclusion it is suggested that MRT could be possible if the "normal" geometry of the wires of a heart pacemaker is ensured and an open MR system is used.
I. M. Graf, G. Seemann, and O. Dössel. Theoretical research on the influence of defibrillator paddle position on the human ventricular myocardium. In Proc. CinC, vol. 31, pp. 97-101, 2004
Defibrillation of the heart is used widely to resuscitate pa tients with fibrillating heart, being the most effective ther apy for this otherwise lethal disturbance of cardiac rhythm. The basic electrophysilogical mechanisms of this proce dure are not well understood. The aim of this work is to in vestigate the conditions that influence the so called virtual electrodes that appear in human ventricular myocardium and also their effects. A two-dimensional and a three dimensional computer model of cardiac tissue is used. For this the temporal evolution of the transmembrane voltage is studied until the entire tissue is repolarized, the needed time interval being around 400 ms.
I. M. Popp, G. Seemann, and O. Dössel. Investigation of electrical defibrillation of chaotically fibrillating human ventricular myocardium in a computer model. In Proceedings of the 31st International Congress on Electrocardiology, pp. 148-151, 2004
Defibrillation is the most important measure of resuscitation aiming at restoration of the physiological heart rhythm. A complete understanding of the defibrillation mechanism has not been achieved yet. The research presented in this article gives a mathematical computer simulation of the defibrillation of chaotically fibrillating human ventricular myocardium. The study was done with a model representing a three-dimensional wedge of human ventricular myocardial tissue. The cellular electrophysiology was described with the Priebe-Beuckelmann model. The electrical activity of the cardiac tissue was calculated with a bidomain model. A spiral wave was induced in the myocardium with standard S1-S2 protocols. The myocardium was brought into a chaotically fibrillating state by breaking the spiral wave. Few hundred milliseconds after the chaotically fibrillation started, monophasic electrical defibrillating shocks were applied through planar electrodes. The defibrillation shocks were applied at different moments. At each chosen moment we studied both cases of electrical polarity. The reaction of myocardium was studied during the following 400 ms. The results are indicating important information related to the factors, which are influencing the defibrillation success.
The purpose of this study is to develop a computer model-based planning environment for therapeutically cardiac interventions, i.e. surgical or catheter ablation procedures in atrial cases and placing pacemaker electrodes in biventricular pacing. Existing mathematical models are used to simulate the electrophysiology on an anatomical pig model during a heart cycle. The results of these models were validated in multiple domestic pig animal experiments. We found that the models created enable us to simulate the electrical behaviour of the heart nearly in real time and that it reproduces the properties of the heart in atrial flutter and in ventricular pacing with different pacing locations. The results of computer-based simulations may lead to a better understanding of cardiac rhythm disorders and the development of new, less invasive operative techniques.
Cardiac electro-mechanical models are valuable tools to gain insights in physiology and pathophysiology of the heart. Progressive models can be created by fusion of various basic models. In this work biventricular models of cardiac electro-mechanics were developed by fusion of anatomical, electrical, and mechanical models. The importance of anatomical modeling was researched by inclusion of two different anatomical models, i.e. an analytical and a magnetic resonance diffusion tensor imaging based model. The fused models were applied in simulations of physiological behavior and results of these were analyzed. Significant difference of deformation were found, which can be attributed to the anatomical models. The analysis emphasized the importance of appropriate anatomical modeling for simulations of cardiac mechanics.
F. B. Sachse, and B. Taccardi. Visualization of Electrical Current Flow with a New Streamline Technique: Application in Mono- and Bidomain Simulations of Cardiac Tissue. In Proc. IEEE EMBS, pp. 1846-1849, 2004
G. Seemann, D. L. Weiß, F. B. Sachse, and O. Dössel. Familial atrial fibrillation: simulation of the mechanisms and effects of a slow rectifier potassium channel mutation in human atrial tissue. In Proc. Computers in Cardiology, vol. 31, pp. 125-128, 2004
Atrial fibrillation (AF) is a critical pathology due to the risk of secondary diseases like thromboemboli and ventricular arrhythmia. A recent study identified a familial type of AF based on a mutation influencing the cardiac IKs channel. The mutant channel is characterized by a gain-of-function and a nearly linear current-voltage relationship. The kinetics and density of IKs in a model of atrial myocytes was adjusted to the measured characteristic to describe the mechanisms and effects of the mutation. A schematic anatomical model of the right atrium was designed to simulate the excitation propagation. The action potential duration of the mutant cell was reduced to 105 ms and the effective refractory period to 148 ms. Both factors lead to a reduction in wavelength and thus the risk of an initiation and perpetuation of AF rises. The results support the understanding of the complex behavior of cardiac cells. The described model will be used to investigate AF and potential treatments.
Y. Shang, and O. Dössel. Construction of cardiac anatomical models using deformable model methods. In Bildverarbeitung für die Medizin 2004, pp. 209-213, 2004
Y. Shang, and O. Dössel. Statistical 3D shape-model guided segmentation of cardiac images. In Proc. Computers in Cardiology, 2004
S. Fuhrhop, S. Seitz, and S. Lamparth. Konzeption und Entwicklung einer Smart-Clothes Plattform zur aktiven Körperklimatisierung. Universität Karlsruhe (TH), Institut für Technik der Informationsverarbeitung. Dissertation. 2004
R. Müller. Schnelle volumenbasierte Visualisierung unter Berücksichtigung von lokalen Verschiebungen. Institute of Biomedical Engineering, Universität Karlsruhe (TH). Dissertation. 2004
C. H. Riedel. Planare induktive Impedanzmessverfahren in der Medizintechnik. Universität Karlsruhe (TH), Institut für Biomedizinische Technik. Dissertation. 2004
O. Skipa. Linear inverse problem of electrocardiography: epicardial potentials and transmembrane voltages. Helmes Verlag Karlsruhe. Dissertation. 2004
F. Toth. Vergleich zweier Verfahren zur Segmentation von medizinischen Bilddaten mittels topologisch veränderbarer Aktiver Konturen. Universität Karlsruhe (TH), Institut für Biomedizinische Technik. Dissertation. 2004
M. Völker. Weiterentwicklung einer planaren Sensormatrix für die berührungslose Impedanzmessung. Universität Karlsruhe (TH), Institut für Biomedizinische Technik. Dissertation. 2004
H. Ying. Investigation of atrial fibrillation induced remodeling in human right atrium: a simulation study. Institute of Biomedical Engineering, Universität Karlsruhe (TH). Dissertation. 2004
AF is a common arrhythmia, arising from the disturbance of initiation and propagation of excitation pattern in atrial tissue. AF itself causes progressive electrophysiological and/or structural changes, which promote the initiation or perpetuation of AF. The involvement of electrophysiological changes to accom- plish the pathological adaptation from SR to the fibrillatory rhythm is termed as electrophysiological remodeling. In the present work, we investigate the re- modeling effects in response to the restored SR by cardioversion in RA in order to provide insights for the maintenance and progression of AF.A schematic anatomical right atrial model was established to simulate the wave propagation. It is composed of the SA node, which is the initiator of the physiological electrical activation, and the main musculature in RA: the terminal crest, pectinate muscles and the working myocardium, among which CT and PM are anisotropic and fast-conducting. Heterogeneous electrical ac- tivities (APD and morphology) in the different regions of RA and SA node are taken into account through modification of the parameters in the Courte- manche cellular model, which can reproduce the action potential (AP) of human atrial myocytes. The cellular electrical interconnection was described by using a monodomain approach combined with a finite difference method. Various conductivities were assigned to the model of healthy tissue to achieve the con- duction velocity approximating the experimental data obtained from human atria.At first, the cellular model was modified by incorporating the chronic AF in- duced electrophysiological changes reported in  to acquire the AP adapted from the SR to the fibrillatory rhythm. The individual impact of each elec- trophysiological change on the remodeling effect was investigated. Then the excitation propagation was simulated adopting the same method mentioned above with the schematic RA model in the physiological and remodeling case, respectively. In both cases the activation sequences were evaluated by measur- ing ERP, APD90, the conduction velocity, the activation time of RA and the heart rate.The remarkably abbreviated APD90 and ERP, and the attenuated rate ac- commodation of APD90 and ERP are the critical components of the results, which are the important characteristic of chronic AF. These effects are as- sociated with the decreased ICaL, Ito and enhanced IK1. Attenuated ERP rate-adaptation and short ERP cause the considerably decreased wavelength of atrial refractoriness (product of conduction velocity and ERP), thus allowing more wavelets to coexist in a given tissue mass. The enhanced vulnerability to propagate the premature depolarization promotes to the maintenance and perpetuation of AF. Fast atrial rate has been proposed as a potential trigger of electrophysiological remodeling by preventing the completely depolarised rest- ing potential and by Ca2+ overload per cardiac cycle. Remodeling may be a cellular adapative response at high heart rate to keep the APD short, thus op- pose Ca2+ overload, but at the expense of re-entry promoting ERP-shortening.The principal features of remodeling AP are reconstructed in this model. They are consistent with the clinical and experimental measurements. The sim- ulated impulse wavefront underlying the Courtemanche model with remodeling conditions resembles excitation propagation in the patients with chronic AF af- ter cardioversion. The relations between the abnormal propagating properties in tissue model and the cellular electrophysiological changes are elucidated. We have sought an explanation for AF begets AF at the cellular electrophysiolog- ical level. The remodeled RA model presents a dysfunctional substrate, which is more probable to induce and perpetuate AF.In the further work, it can be extended to simulate the AF effect, e.g. initi- ation and maintenance of re-entry wavelets in both atria, as well as the whole heart, if the triggers of AF are involved. The anatomical features will be cap- tured more realistically in future models. New pharmacological approaches to stabilize the atrial rhythm can be validated utilizing this model. In the present work, we employed uniform conductivity in the working myocardium and a monodomain formulation. In future, anisotropic and more detailed descrip- tion of cellular connection will be included. The remodeling conditions can be incorporated in CT and PM to match the clinical experimental data more accurately.
Student Theses (2)
K. Chaisaowong. Modeling of human cardiac force development: Quantitative description from myofilament to myocardium. Institute of Biomedical Engineering, Universität Karlsruhe (TH). Diplomarbeit. 2004
Computer simulations of cardiac force development, based on mathematical models, lead to better understanding of the cardiac contractile function and its pathological behavior. In this work, quantitative data concerning cardiac force development of micro- scopic myocytes and macroscopic specimen were acquired from publications, which report from experiments. A material database quantified by species, e.g. human, mice, and cow, specimen, e.g. left ventricular papillary, and Purkinje myocyte, and pathology, e.g. dilatated cardiomyopathy, and diabetes, was gen- erated. The adaptation of the cardiac force development model using new quan- titative microscopic calcium sensitivity via re-parameterization techniques was accomplished. Force development simulations were also performed, on species- and specimen-specific and pathologic cell models. A species- and specimen- specific method to scale the calculated tension using the generated database was implemented. The species- and specimen-specific scalation of calculated tension was also performed. Through the integration of quantitative informa- tion, a more close-to-reality model of force development was created.In this work, applied methods and materials were also described. Mathematical principles, used for this purpose, i.e. continuum mechanics, numerical optimiza- tion and numerical minimization, are described in the second chapter. A deep insight into the structures of cardiac myocyte, which involve force development and cellular contraction, are provided in the third chapter. The forth chapter describes the electrophysiology of ionic channels, especially the gap junction. The electrophysiological model used for this work was also introduced. The fifth chapter explains in detail how an electrical excitation begins, spreads, and ends up on the triggered contraction of myocyte. The excitation-contraction coupling mechanism of the cardiac force development was described in detail. The sixth chapter shows the measurement construction and the quantifying definition of the experimental data acquisition concerning both calcium sensi- tivity and force generation. The database acquired for this diploma thesis is also displayed in the sixth chapter. In chapter seven, modelings of the force development in myofibrillar level, e.g. calcium triggering and the cross-bridge building, were described. The former and up-to-date cardiac force development models are listed and explained.Finally in the last chapter, results of the integration of calcium sensitivity, simulations with new re-parameterized cellular force development models, and species- and specimen-specific scalation of calculated tension in deformation model are shown. The eighth chapter provides an overview of the improvement history of the force development models.
N. Ludewig. Aufbau einer planaren Sensormatrix für die berührungslose Impedanzmessung mit Multiplexeinheit. Universität Karlsruhe (TH), Institut für Biomedizinische Technik. Diplomarbeit. 2004