Browsing by Subject "Alternans"

Now showing 1 - 4 of 4
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    The anti-arrhythmic effects of constant diastolic interval pacing in a numerical model of a canine cardiac ventricular fiber
    (2016-06) Johnson, Christopher
    Beat to beat changes in action potential duration (APD) are known as alternans. Alternans are precursors for cardiac arrhythmias that may lead to heart failure and sudden cardiac death. Sudden cardiac death makes up 15-20% of all deaths annually in the United States (Deo, [28]). Alternans are known to form in association with periodic pacing protocol, during which the basic cycle length (BCL) is held constant. Periodic pacing incorporates feedback from the previous action potential, allowing for the formation of alternans. Constant diastolic interval (DI) pacing relies on the elimination of feedback within the system, and through the elimination causes the suppression of alternans. It has previously been shown that alternans suppression within a single cell model is possible (McIntyre, [22]). This research focuses on the presence and behavior of alternans in a 150 cell (1.5cm) and a 300 cell (3cm) cable during constant BCL and constant DI pacing. Alternans did appear for constant DI pacing for DI values lower than 20ms, representing a non-physiological range. However, we found that alternans could be controlled using a constant DI pacing protocol for both a short and long cable when using physiological ranges for DI, above 30ms.
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    Effect of constant-DI pacing on single cell cardiac dynamics
    (2020-09) Parthiban, Preethy
    Cardiac alternans, beat-to-beat alternations in action potential duration (APD), is a precursor to fatal arrhythmias such as ventricular fibrillation (VF). Previous research has shown that voltage driven alternans can be suppressed by application of constant diastolic interval (DI) pacing protocol. However, the effect of constant-DI pacing on cardiac cell dynamics and its interaction with the intracellular calcium cycle remains to be determined. Therefore, we aimed to examine the effects of constant-DI pacing on the dynamical behavior of isolated cardiac myocytes along with the influence of voltage-calcium (V-Ca) coupling on these changes. Cardiac cell dynamics were analyzed in a non-linear neighborhood close to the bifurcation point using a hybrid pacing protocol, a combination of periodic and constant-DI pacing. We demonstrated that in a small region beneath the bifurcation point constant-DI pacing caused the cardiac cell to remain alternans-free after switching to the constant-BCL pacing, thus introducing a region of bistability (RB). Strong V-Ca coupling increased the size of the RB. Overall, our findings demonstrate that experimental constant-DI pacing on cardiac cells with strong V-Ca strength may induce permanent changes to cardiac cell dynamics increasing the utility of constant-DI pacing.
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    Eigenvalue based alternans prediction and the effects of heart rate variability on alternans formation
    (2013-06) Kakade, Virendra Vilas
    Ventricular fibrillation, a leading cause of death in the US, is an instability observed at the whole heart level which may result from the alternation of action potential viz. alternans at the cellular level. Previous approaches to predict alternans formation are based on the slope of the restitution curve which is the relation between the action potential duration (APD) and the duration of the preceding diastolic interval (DI). These approaches propose that alternans exists when the slope of this curve is greater than one and ceases to exist otherwise. However restitution based approaches have not been successful in all cases. One of the shortcomings of restitution approach is the non-uniqueness of the restitution curve which results from the variety of pacing protocols used to construct it. This has lead to observations in which alternans existed when the slope was less than one and vice a versa. Moreover restitution approaches use just one measurement from each action potential(AP). Another shortcoming of these approaches is periodic pacing, which is employed to attain the responses (APD and DI) at different basic cycle lengths (BCL) to construct the restitution curve. Upon analysis of electrocardiograms, it is evident that natural pacing is not periodic and exhibits rate variability which can be seen from measurement of RR intervals (which are analogous to BCL) over time. It would be beneficial to develop a method which is not very related to the restitution approach to predict alternans formation and which would not necessitate the generation of a curve and thus reduce errors introduced due to slope calculation. Such a method could also use multiple measurements from each AP to characterize it. Also, it would be beneficial to study the effects of introducing variability in pacing, on alternans formation. Analysis of such data would give us some valuable insight into the complex phenomenon of alternans. With these two shortcomings in sight two studies were conducted with specific aims as follows:Aim1: Apply a dominant eigenvalue method to predict alternans formation in the rabbit heart. A dominant eigenvalue based alternans prediction was recently developed and tested on data obtained from single cell numerical simulation data. I applied this technique at whole heart level to test whether alternans formation could be predicted using a eigenvalue calculated at each BCL from AP response data. I found that the eigenvalue showed decreasing trend towards the value of -1 as BCL was decreased and approached alternans onset. Aim2: Study the effect of introducing rate variability in pacing on a ionic model of a single cell. Ionic model of a single cell was paced using two protocols which introduced variability in the pacing rate by either varying the BCL or DI to test the effects on alternans formation. It was found that introducing variability using first method (varying BCL) lead to alternans formation over wider range of BCL than without variability. The second method (varying DI) however did not give rise to alternans in the model with or without variability.
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    The importance of calcium cycling and mitochondria in the local onset of alternans in the heart
    (2014-05) Visweswaran, Ramjay
    Action potential duration (APD) alternans can be accompanied by alternans in intracellular calcium, leading to electromechanical alternans. Electromechanical alternans is considered a substrate for ventricular fibrillation, especially during pathophysiological conditions such as ischemia. The work in thesis seeks to elucidate the spatio-temporal evolution of alternans and to investigate the potential pathways through which they occur. High resolution mapping was used to simultaneously map membrane voltage and intracellular calcium in normal rabbit hearts. By mapping both parameters simultaneously in the same region of the heart, we were able to reveal that instability in calcium cycling plays a primary role in the development of EM alternans in the whole heart. Further, we were able to apply a special restitution portrait analysis to predict the onset of both calcium and APD alternans before it occurs. We also wanted to elucidate the mechanisms behind the increased incidences of arrhythmias during ischemia. By simulating ischemic and mitochondrial dysfunction in isolated rabbit hearts, we were able to show that mitochondrial stress caused by uncoupling of the mitochondria is responsible for early occurrence of both APD and calcium alternans in the heart, which in turn creates a substrate to ventricular arrhythmias. Thus, uncoupling of the mitochondrial network that occurs during ischemia might be the primary reason for increased incidences of arrhythmias in the heart during ischemia. Overall, this study improves our knowledge of alternans and their basic underlying mechanism which can be used in the development of better treatment and/or prevention strategies. Development of techniques to predict alternans before it occurs would be a valuable clinical tool, especially for use in implantable pacemakers paving the way for pre-emptive interventions. In addition, elucidating the mechanism or pathways of alternans formation would lead to targeted drug treatments to prevent alternans and thus, VF and sudden cardiac death.