Publications by authors named "Timothy D Butters"

Rapid atrial arrhythmias such as atrial fibrillation (AF) predispose to ventricular arrhythmias, sudden cardiac death and stroke. Identifying the origin of atrial ectopic activity from the electrocardiogram (ECG) can help to diagnose the early onset of AF in a cost-effective manner. The complex and rapid atrial electrical activity during AF makes it difficult to obtain detailed information on atrial activation using the standard 12-lead ECG alone.

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X-ray computed tomography (XCT) has been shown to be an effective imaging technique for a variety of materials. Due to the relatively low differential attenuation of X-rays in biological tissue, a high density contrast agent is often required to obtain optimal contrast. The contrast agent, iodine potassium iodide ([Formula: see text]), has been used in several biological studies to augment the use of XCT scanning.

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Sheep are often used as animal models for experimental studies into the underlying mechanisms of cardiac arrhythmias. Previous studies have shown that biophysically detailed computer models of the heart provide a powerful alternative to experimental animal models for underpinning such mechanisms. In this study, we have developed a family of mathematical models for the electrical action potentials of various sheep atrial cell types.

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Computer models provide a powerful platform for investigating mechanisms that underlie atrial rhythm disturbances. We have used novel techniques to build a structurally-detailed, image-based model of 3-D atrial anatomy. A volume image of the atria from a normal sheep heart was acquired using serial surface macroscopy, then smoothed and down-sampled to 50 μm(3) resolution.

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Background: Computer models that capture key features of the heterogeneous myofiber architecture of right and left atria and interatrial septum provide a means of investigating the mechanisms responsible for atrial arrhythmia. The data necessary to implement such models have not previously been available. The aims of this study were to characterize surface geometry and myofiber architecture throughout the atrial chambers and to investigate the effects of this structure on atrial activation.

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Heterogeneity in the electrical action potential (AP) properties can provide a substrate for atrial arrhythmias, especially at rapid pacing rates. In order to quantify such substrates, we develop a family of detailed AP models for canine atrial cells. An existing model for the canine right atrial (RA) myocyte was modified based on electrophysiological data from dog to create new models for the canine left atrium (LA), the interatrial Bachmann's bundle (BB), and the pulmonary vein (PV).

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Rationale: Familial sick sinus syndrome (SSS) has been linked to loss-of-function mutations of the SCN5A gene, which result in decreased inward Na(+) current, I(Na). However, the functional role of I(Na) in cardiac pacemaking is controversial, and mechanistic links between mutations and sinus node dysfunction in SSS are unclear.

Objective: To determine mechanisms by which the SCN5A mutations impair cardiac pacemaking.

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