20 research outputs found
Regional Dominant Frequency: A New Tool for Wave Break Identification During Atrial Fibrillation
Cardiac mapping systems are based on the time/frequency feature analyses of intracardiac electrograms recorded from individual bipolar/unipolar electrodes. Signals from each electrode are processed independently. Such approaches fail to investigate the interrelationship between simultaneously recorded channels of any given mapping catheter during atrial fibrillation (AF). We introduce a novel signal processing technique that reflects regional dominant frequency (RDF) components. We show that RDF can be used to identify and characterize variation and disorganization in wavefront propagation- wave breaks. The intracardiac electrograms from the left atrium of 15 patients were exported to MATLAB and custom software employed to estimate RDF and wave break rate (WBR). We observed a heterogeneous distribution of both RDF and WBR; the two measures were weakly correlated (0.3; p < 0.001). We identified locations of AF or atrial tachycardia (ATach) termination and later compared offline with RDF and WBR maps. We inspected our novel metrics for associations with AF termination sites. Areas associated with AF termination demonstrated high RDF and low WBR (↑RDF,↓WBR). These sites were present in 14 of 15 patients (mean 2.6 ± 1.2 sites per patient; range, 1–4 sites), 43% situated within the pulmonary veins. In nine patients where AF terminated to sinus rhythm (6) or ATach (3), post-hoc analysis demonstrated all ↑RDF,↓WBR sites were ablated and correlated with AF termination sites. The proposed RDF signal processing tools can be used to identify and quantify wave break, and the combined use of these two novel metrics can aid characterization of AF. Further prospective studies are warranted
Cardiomyocyten im Chaos: Makroskopische Untersuchungen kardialer Arrhythmien in-vitro unter dem Einfluss elektrischer Pulsfolgen und Parameteränderungen
Ein Charakteristikum für viele physiologische und pathologische Zustände in biologischen Systemen ist eine komplexe raum-zeitliche Dynamik. So wird z.B. bei kardialer Fibrillation die synchrone Kontraktion des Herzens durch wirbelartig rotierende Erregungswellen unterbrochen, welche oft zu chaotischer Erregungsweiterleitung führen. Gegenstand aktueller Forschung sind insbesondere die zugrunde liegenden Mechanismen der Entstehung und Terminierung solcher Turbulenzformen. Hier wurde ein experimenteller Versuchsaufbau etabliert, der die Untersuchung kardialer Musterbildung in der Zellkultur erlaubt.For many physiological and pathological states in biological systems a complex spatio-temporal dynamic is characteristic. For example during fibrillation, synchronous contraction of the heart is disrupted by vortex-like rotating waves, resulting in complex and often chaotic excitation patterns. One focus of research is the clearing of underlying mechanisms of development and termination of such turbulence. Here an experimental setup was established, which allows investigation of cardiac pattern formation in two dimensional cell cultures under several conditions
Nonlinear physics of electrical wave propagation in the heart: a review
The beating of the heart is a synchronized contraction of muscle cells
(myocytes) that are triggered by a periodic sequence of electrical waves (action
potentials) originating in the sino-atrial node and propagating over the atria and
the ventricles. Cardiac arrhythmias like atrial and ventricular fibrillation (AF,VF)
or ventricular tachycardia (VT) are caused by disruptions and instabilities of these
electrical excitations, that lead to the emergence of rotating waves (VT) and turbulent
wave patterns (AF,VF). Numerous simulation and experimental studies during the
last 20 years have addressed these topics. In this review we focus on the nonlinear
dynamics of wave propagation in the heart with an emphasis on the theory of pulses,
spirals and scroll waves and their instabilities in excitable media and their application
to cardiac modeling. After an introduction into electrophysiological models for action
potential propagation, the modeling and analysis of spatiotemporal alternans, spiral
and scroll meandering, spiral breakup and scroll wave instabilities like negative line
tension and sproing are reviewed in depth and discussed with emphasis on their impact
in cardiac arrhythmias.Peer ReviewedPreprin
Stabilité de la réentrée anatomique dans le muscle cardiaque et annihilation par un protocole à deux stimulations : études de modélisation et aspects expérimentaux
Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal
Modelling the interaction between induced pluripotent stem cells derived cardiomyocytes patches and the recipient hearts
Cardiovascular diseases are the main cause of death worldwide. The single biggest killer is represented by ischemic heart disease. Myocardial infarction causes the formation of non-conductive and non-contractile, scar-like tissue in the heart, which can hamper the heart's physiological function and cause pathologies ranging from arrhythmias to heart failure. The heart can not recover the tissue lost due to myocardial infarction due to the myocardium's limited ability to regenerate. The only available treatment is heart transpalant, which is limited by the number of donors and can elicit an adverse response from the recipients immune system. Recently, regenerative medicine has been proposed as an alternative approach to help post-myocardial infarction hearts recover their functionality. Among the various techniques, the application of cardiac patches of engineered heart tissue in combination with electroactive materials constitutes a promising technology. However, many challenges need to be faced in the development of this treatment. One of the main concerns is represented by the immature phenotype of the stem cells-derived cardiomyocytes used to fabricate the engineered heart tissue. Their electrophysiological differences with respect to the host myocardium may contribute to an increased arrhythmia risk. A large number of animal experiments are needed to optimize the patches' characteristics and to better understand the implications of the electrical interaction between patches and host myocardium. In this Thesis we leveraged cardiac computational modelling to simulate \emph{in silico} electrical propagation in scarred heart tissue in the presence of a patch of engineered heart tissue and conductive polymer engrafted at the epicardium. This work is composed by two studies. In the first study we designed a tissue model with simplified geometry and used machine learning and global sensitivity analysis techniques to identify engineered heart tissue patch design variables that are important for restoring physiological electrophysiology in the host myocardium. Additionally, we showed how engineered heart tissue properties could be tuned to restore physiological activation while reducing arrhythmic risk. In the second study we moved to more realistic geometries and we devised a way to manipulate ventricle meshes obtained from magnetic resonance images to apply \emph{in silico} engineered heart tissue epicardial patches. We then investigated how patches with different conduction velocity and action potential duration influence the host ventricle electrophysiology. Specifically, we showed that appropriately located patches can reduce the predisposition to anatomical isthmus mediated re-entry and that patches with a physiological action potential duration and higher conduction velocity were most effective in reducing this risk. We also demonstrated that patches with conduction velocity and action potential duration typical of immature stem cells-derived cardiomyocytes were associated with the onset of sustained functional re-entry in an ischemic cardiomyopathy model with a large transmural scar. Finally, we demonstrated that patches electrically coupled to host myocardium reduce the likelihood of propagation of focal ectopic impulses. This Thesis demonstrates how computational modelling can be successfully applied to the field of regenerative medicine and constitutes the first step towards the creation of patient-specific models for developing and testing patches for cardiac regeneration.Open Acces
Developing a fluorescence-based tool to measure noradrenaline transporter function in cardiovascular tissue
Sympathetic noradrenergic transmission in both the heart and vasculature is modulated at central, ganglionic, and end-organ sites. It is ultimately within the neuroeffector junction where the dynamic interplay between noradrenaline (NAd) release and its subsequent reuptake by the noradrenaline transporter (NAT) that predominately determines the junctional availability of the neurotransmitter. However, despite the fact that NAT dysfunction is implicated in many cardiovascular diseases, the mechanisms that govern transporter modulation remain poorly defined due to the limited methodologies available. This study demonstrates the development and optimisation of a novel, fluorescence-based technique, NTUA (Neurotransmitter Transporter Uptake Assay), that permits dynamic measurements of NAT function at high spatiotemporal resolutions in whole organ preparations ex vivo. This technique was then used to explore putative NAT regulators. It was discovered that several known release-inhibiting modulators, such as the muscarinic acetylcholine receptor, ⍺2-adrenoceptor (⍺2AR), and cannabinoid type I receptor (CB1R), also suppress NAT function. Importantly, the neuromodulatory roles of ⍺2AR and CB1R were also uncovered during bouts of sympathetic neuronal activity, which provides further insight into the complexity of net noradrenergic transmission. Moreover, the future potential for NTUA as an intravital stain to monitor disease progression in vivo was demonstrated by its use to simultaneously detect for changes in NAT function and sympathetic nerve density in a pre-clinical animal model of obstructive sleep apnoea, a disease with complex cardiovascular implications. These data, amongst others, show that NTUA will help future research into junctional NAd availability and hence the study of sympathetic transmission in the cardiovascular system