Madison S. Spach

Bio: Madison S. Spach is an academic researcher from Duke University. The author has contributed to research in topics: QRS complex & Repolarization. The author has an hindex of 49, co-authored 143 publications receiving 9752 citations. Previous affiliations of Madison S. Spach include University of Pennsylvania.

Relating extracellular potentials and their derivatives to anisotropic propagation at a microscopic level in human cardiac muscle. Evidence for electrical uncoupling of side-to-side fiber connections with increasing age.

Abstract: Elucidation of the mechanisms of cardiac conduction disturbances leading to reentry will require resolution of the details of multidimensional propagation at a microscopic size scale (less than 200 micron). In practice, this will necessitate the combined analysis of extracellular and transmembrane action potentials. The purpose of this paper is to demonstrate the relationships between the time derivatives of the extracellular waveforms and the underlying action potentials in the experimental analysis of anisotropic propagation at this small size scale, and apply these relationships to human atrial muscle at different ages. The extracellular waveforms and their derivatives changed from a smooth contour during transverse propagation in young preparations to complex polyphasic waveforms in the older preparations. The major problem was to estimate the size and location of small groups of fibers that generated the complex waveforms in the older preparations. We found dissimilarities in the derivatives that distinguished source (bundle) size from the distance of the source to the measurement site. The differences in the extracellular waveforms and their derivatives indicated that there was electrical uncoupling of the side-to-side connections between small groups of fibers with aging. These changes produced a prominent zigzag course of transverse propagation at a microscopic level which, in turn, accounted for the increased complexity of the waveforms. The waveform differences also correlated with the development of extensive collagenous septa that separated small groups of fibers. The electrophysiological consequence was an age-related decrease in the "effective" transverse conduction velocities to the range of the very slow conduction (less than 0.08 m/sec) which makes it possible for reentry to occur in small regions of cardiac muscle with normal cellular electrophysiological properties.

The functional role of structural complexities in the propagation of depolarization in the atrium of the dog. Cardiac conduction disturbances due to discontinuities of effective axial resistivity.

Abstract: Structural complexities produced by the inhomogeneous distribution of the connections between cells and between muscle bundles have previously been considered to be of minor importance in the propagation of depolarization in cardiac muscle; conduction disturbances usually are attributed to changes in membrane properties along the course of the fibers. However, we observed marked effects of these connections on the velocity and the safety factor of propagation in atrial muscle under normal and abnormal conditions. First, within individual muscle bundles, intermittent connective- tissue septa were associated with localized dissociation of excitation when propagation occurred in the transverse direction, but not when it occurred in the longitudinal direction. Second, at sites where muscle bundles branch or join with other bundles, we observed abrupt slowing of normal action potentials and changes in the shape of the extracellular waveform. We also studied such a junction in a computer simulation of propagation and found that the local delay of propagation and the change in the shape of the extracellular waveform could only be accounted for by an abrupt change in the effective axial resistivity in the direction of propagation. Under normal conditions, enough depolarizing current is coupled across such discontinuities to maintain propagation. However, when the maximum membrane depolarizing current was reduced by increasing the extracellular potassium concentration or by premature stimulation, block occurred at these sites. We observed that most known cardiac conduction disturbances considered to require longer refractory periods in the direction of propagation (e.g., local conduction delay, decremental conduction, block, and reentry) can be produced by the effects on propagation of such discontinuities of effective axial resistivity. The results indicate that models of propagation that ignore the inhomogeneous and multidimensional distribution of cell-to-cell connections produce incomplete, and sometimes incorrect, descriptions of normal and abnormal propagation in cardiac muscle.

Influence of the passive anisotropic properties on directional differences in propagation following modification of the sodium conductance in human atrial muscle. A model of reentry based on anisotropic discontinuous propagation.

Abstract: Available models of circus movement reentry in cardiac muscle and of drug action on reentrant arrhythmias are based on continuous medium theory, which depends solely on the membrane ionic conductances to alter propagation. The purpose of this study is to show that the anisotropic passive properties at a microscopic level highly determine the propagation response to modification of the sodium conductance by premature action potentials and by sodium channel-blocking drugs. In young, uniform anisotropic atrial bundles, propagation of progressively earlier premature action potentials continued as a smooth process until propagation ceased simultaneously in all directions. In older, nonuniform anisotropic bundles, however, premature action potentials produced either unidirectional longitudinal conduction block or a dissociated zigzag type of longitudinal conduction (a safer type of propagation, similar to transverse propagation). Directional differences in the velocity of premature action potentials demonstrated that anisotropic propagation was necessary for a reentrant circuit to be contained within an area of 50 mm2, even with very short refractory periods. Quinidine produced Wenckebach periodicity, which disappeared after acetylcholine shortened the action potential. Quinidine also produced use-dependent dissociated zigzag longitudinal conduction in the older, nonuniform anisotropic bundles but not in the young, uniform anisotropic bundles. The electrophysiological consequence was that propagation events differed in an age-related manner in response to the same modification of the sodium conductance. The electrical events at microscopic level showed that conditions leading to obliteration of side-to-side electrical coupling between fibers (e.g., aging and chronic hypertrophy) provide a primary mechanism for reentry to occur within very small areas (1-2 mm) due to a variety of propagation phenomena that do not occur in tissues with tight electrical coupling in all directions.

Extracellular potentials related to intracellular action potentials during impulse conduction in anisotropic canine cardiac muscle.

Abstract: This paper considers a quantitative description of intracellular and transmembrane currents in anisotropic muscle, with emphasis on the factors that determine the extracellular potentials. Although Vmax of the intracellular action potential had no relation to changes in conduction velocity in anisotropic tissue with constant membrane properties, the extracellular waveforms were quite sensitive to velocity changes. Large amplitude biphasic deflection occurred in the fast areas, and in the slow areas the waveforms were of lower amplitude and triphasic in shape; i.e., negative potentials preceded the biphasic positive-negative deflection. The extracellular potentials were simulated on the bases of a model of intracellular currents, and the theoretical and measured results showed good agreement. In tissue with anisotropic conductivity, the relationship between the spatial intracellualr potential gradient and the magnitude of the extracellular potential of the excitation wave was opposite to the classical relationship in isotropic tissue. Due to the influence of the effective intracellular conductivity on the spread of intracellular currents and on conduction velocity, in anisotropic tissue the extracellular potential decreased as the intracellular potential gradient increased. The peak values of the positive and negative potentials and the spatial distribution of the potential gradients varied considerably along the activation front. These findings were accounted for by differences in the distribution and spatial extent of the transmembrane currents, which were determined by the intracellular currents. The theoretical analysis showed that intracellular and transmembrane currents were proportional to the local conduction velocities of the wavefront. Thereby, it was not possible to have a "uniform layer" of current when there were differences in conduction velocity along the length of the excitation wave. The implications of the analysis are considerable, since the gratifying agreement between the theoretical and measured results indicates that the details of the extracellular waveforms can be explained on the basis of the distribution of intracellular currents; i.e., extracellular potentials provide a sensitive index of intracellular current flow.

Spontaneous Initiation of Atrial Fibrillation by Ectopic Beats Originating in the Pulmonary Veins

Abstract: Background Atrial fibrillation, the most common sustained cardiac arrhythmia and a major cause of stroke, results from simultaneous reentrant wavelets. Its spontaneous initiation has not been studied. Methods We studied 45 patients with frequent episodes of atrial fibrillation (mean [±SD] duration, 344±326 minutes per 24 hours) refractory to drug therapy. The spontaneous initiation of atrial fibrillation was mapped with the use of multielectrode catheters designed to record the earliest electrical activity preceding the onset of atrial fibrillation and associated atrial ectopic beats. The accuracy of the mapping was confirmed by the abrupt disappearance of triggering atrial ectopic beats after ablation with local radio-frequency energy. Results A single point of origin of atrial ectopic beats was identified in 29 patients, two points of origin were identified in 9 patients, and three or four points of origin were identified in 7 patients, for a total of 69 ectopic foci. Three foci were in the right atrium...

2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS

Abstract: The Task Force for the management of atrial fibrillation of the European Society of Cardiology (ESC) Developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC Endorsed by the European Stroke Organisation (ESO)

Atrial Fibrillation Begets Atrial Fibrillation A Study in Awake Chronically Instrumented Goats

Abstract: Background In this study we tested the hypothesis that atrial fibrillation (AF) causes electrophysiological changes of the atrial myocardium which might explain the progressive nature of the arrhythmia. Methods and Results Twelve goats were chronically instrumented with multiple electrodes sutured to the epicardium of both atria. Two to 3 Weeks after implantation, the animals were connected to a fibrillation pacemaker which artificially maintained AF. Whereas during control episodes of AF were short lasting (6±3 seconds), artificial maintenance of AF resulted in a progressive increase in the duration of AF to become sustained (>24 hours) after 7.1±4.8 days (10 of 11 goats). During the first 24 hours of AF the median fibrillation interval shortened from 145±18 to 108±8 ms and the inducibility of AF by a single premature stimulus increased from 24% to 76%. The atrial effective refractory period (AERP) shortened from 146±19 to 95±20 ms (−35%) (S1S1, 400 ms). At high pacing rates the shortening was less (−12%...