Effect of anisotropy on ventricular vulnerability to unidirectional block and reentry by single premature stimulation during normal sinus rhythm in rat heart.

Single high-intensity premature stimuli when applied to the ventricles during ventricular drive of an ectopic site, as in Winfree's "pinwheel experiment," usually induce reentry arrhythmias in the normal heart, while single low-intensity stimuli barely do. Yet ventricular arrhythmia vulnerability during normal sinus rhythm remains largely unexplored. With a view to define the role of anisotropy on ventricular vulnerability to unidirectional conduction block and reentry, we revisited the pinwheel experiment with reduced constraints in the in situ rat heart.

The maximal downstroke of epicardial potentials as an index of electrical activity in mouse hearts.

The maximal upstroke of transmembrane voltage (dV(m)/dt(max)) has been used as an indirect measure of sodium current I(Na) upon activation in cardiac myocytes. However, sodium influx generates not only the upstroke of V(m), but also the downstroke of the extracellular potentials V(e) including epicardial surface potentials V(es). The purpose of this study was to evaluate the magnitude of the maximal downstroke of V(es) (|dV(es)/dt (min)|) as a global index of electrical activation, based on the relationship of dV(m)/dt(max) to I(Na).

Epicardial and intramural excitation during ventricular pacing: effect of myocardial structure.

Published studies show that ventricular pacing in canine hearts produces three distinct patterns of epicardial excitation: elliptical isochrones near an epicardial pacing site, with asymmetric bulges; areas with high propagation velocity, up to 2 or 3 m/s and numerous breakthrough sites; and lower velocity areas (<1 m/s), where excitation moves across the epicardial projection of the septum. With increasing pacing depth, the magnitude of epicardial potential maxima becomes asymmetric. The electrophysiological mechanisms that generate the distinct patterns have not been fully elucidated.

Effect of fiber orientation on propagation: electrical mapping of genetically altered mouse hearts.

Background: Epicardial potentials reveal the strong effects of fiber anisotropy, rotation, imbrication, and coupling on propagation in the intact heart. From the patterns of the surface potentials, we can obtain information about the local fiber orientation, anisotropy, the transmural fiber rotation, and which direction the wave front is traveling through the wall. In this study, lessons learned from epicardial potential mapping of large hearts were applied to studies conducted in genetically altered mouse hearts.

Optical mapping of propagation changes induced by elevated extracellular potassium ion concentration in genetically altered mouse hearts.

Unlabelled: Diabetes is associated with high rates of cardiovascular disease and sudden death. Therefore, dissecting specific mechanisms, such as the effects of impaired insulin signaling on cardiac electrophysiology may lead to better diagnosis and treatment. Lack of insulin receptors in mouse myocytes has been shown to reduce repolarizing potassium currents and prolong action potential duration.

Cycle length sequence dependent repolarization dynamics.

Cardiac repolarization, particularly its heterogeneity, is known to play a significant role in arrhythmogenesis. Steepness of cardiac restitution, or the cycle length dependency of repolarization, has also been implicated as a condition that favors occurrence of reentrant arrhythmias. However, most assessments of heterogeneity and restitution are based on static observations and do not directly account for the extent or heterogeneity of dynamic changes.

Spatial methods of epicardial activation time determination in normal hearts.

The purpose of this study was to demonstrate errors in activation time maps created using the time derivative method on fractionated unipolar electrograms, to characterize the epicardial distribution of those fractionated electrograms, and to investigate spatial methods of activation time determination. Electrograms (EGs) were recorded using uniform grids of electrodes (1 or 2 mm spacing) on the epicardial surface of six normal canine hearts. Activation times were estimated using the time of the minimum time derivative, maximum spatial gradient, and zero Laplacian and compared with the time of arrival of the activation wave front as assessed from a time series of potential maps as the standard.

Noninvasive electrocardiogram imaging of substrate and intramural ventricular tachycardia in infarcted hearts.

Objectives: The goal of this study was to experimentally evaluate a novel noninvasive electrocardiographic imaging modality during intramural reentrant ventricular tachycardia (VT).

Background: Myocardial infarction and subsequent remodeling produce abnormal electrophysiologic substrates capable of initiating and maintaining reentrant arrhythmias. Existing noninvasive electrocardiographic methods cannot characterize abnormal electrophysiologic substrates in the heart or the details of associated arrhythmias.

Location of the initiation site of calcium transients and sparks in rabbit heart Purkinje cells.

1. The distribution and localization of Ca2+ transients and Ca2+ sparks in isolated adult rabbit Purkinje cells were examined using confocal microscopy and the Ca2+ indicator fluo-3. 2.

Effects of heart position on the body-surface electrocardiogram.

Previous studies have examined the influence of body position, respiration, and habitus on body surface potentials. However, the authors could only estimate the sources of the effects they documented. Among the proposed origin of changes in body surface potentials from those studies were the position of the heart, alterations in autonomic tone, differences in ventricular blood volume, and variations in torso resistivity.

Estimates of repolarization dispersion from electrocardiographic measurements.

Background: Repolarization dispersion (Rd) is frequently mentioned as a predictor of cardiac abnormalities. We present a new measure of Rd based on the root-mean-square (RMS) curve of an ECG lead set and compare its performance with that of the commonly used QT dispersion (QTd) measure with the use of recovery times measured from directly recorded canine electrograms.

Methods And Results: Using isolated, perfused canine hearts suspended in a torso-shaped electrolytic tank, we simultaneously recorded electrograms from 64 epicardial sites and ECGs from 192 "body surface" sites.

Estimates of repolarization and its dispersion from electrocardiographic measurements: direct epicardial assessment in the canine heart.

This study investigates a technique to estimate dispersion based on the root mean square (RMS) signal of multiple electrocardiographic leads. Activation and recovery times were measured from 64 sites on the epicardium of canine hearts using acute in situ or Langendorff perfused isolated heart preparations. Repolarization and its dispersion were altered by varying cycle length, myocardial temperature, or ventricular pacing site.

Generation of intracellular pH gradients in single cardiac myocytes with a microperfusion system.

This study describes the use of a microperfusion system to create rapid, large regional changes in intracellular pH (pH(i)) within single ventricular myocytes. The spatial distribution of pH(i) in single myocytes was measured with seminaphthorhodafluor-1 fluorescence using confocal imaging. Changes in pH(i) were induced by local external application of NH(4)Cl, CO(2), or sodium propionate.

Noninvasive indices of repolarization and its dispersion.

In experimental studies using Langendorff perfused, isolated canine hearts immersed in a torso-shaped electrolytic tank we studied repolarization and its dispersion using direct epicardial measurements and newly derived, noninvasive body surface indices. Activation recovery intervals (ARIs) measured from 64 epicardial sites based on differences between activation times (ATs) and recovery times (RTs) provided direct measures of repolarization. The indirect, torso surface indices were derived from inflections of the root-mean-square (RMS) voltage of the torso tank surface electrocardiograms recorded simultaneously with the epicardial data.

Mechanisms of the spatial distribution of QT intervals on the epicardial and body surfaces.

Introduction: The role of QT dispersion as a predictor of arrhythmia vulnerability has not been consistently confirmed in the literature. Therefore, it is important to identify the electrophysiologic mechanisms that affect QT duration and distribution. We compared the spatial distributions of QT intervals (QTI) with potential distributions on cardiac and body surfaces and with recovery times on the cardiac surface.

Properties of Ca2+ sparks evoked by action potentials in mouse ventricular myocytes.

1. Calcium sparks were examined in enzymatically dissociated mouse cardiac ventricular cells using the calcium indicator fluo-3 and confocal microscopy. The properties of the mouse cardiac calcium spark are generally similar to those reported for other species.

A field-compatible method for interpolating biopotentials.

Mapping of bioelectric potentials over a given surface (e.g., the torso surface, the scalp) often requires interpolation of potentials into regions of missing data.

High-density epicardial mapping during current injection and ventricular activation in rat hearts.

The purpose of this study is to report new methods for manufacturing precision electrode arrays for recording high-resolution potential distributions from epicardial surfaces of small-animal hearts. Electrode arrays of 64 leads (8 x 8) and 121 leads (11 x 11) were constructed with a tulle substrate to which insulated, fine silver wires (60-micrometer diameter) were attached by knots at mesh node intervals of 540 x 720 micrometers. Insulation was removed at the tips of the knots.

Useful lessons from body surface mapping.

Useful Lessons from Body Surface Mapping. Body surface potential maps (BSMs) depict the time varying distribution of cardiac potentials on the entire surface of the torso. Hundreds of studies have shown that BSMs contain more diagnostic and prognostic information than can be elicited from the 12-lead ECG.

Electrocardiographic imaging: Noninvasive characterization of intramural myocardial activation from inverse-reconstructed epicardial potentials and electrograms.

Background: A recent study demonstrated the ability of electrocardiographic imaging (ECGI) to reconstruct, noninvasively, epicardial potentials, electrograms, and activation sequences (isochrones) generated by epicardial activation. The current study expands the earlier work to the three-dimensional myocardium and investigates the ability of ECGI to characterize intramural myocardial activation noninvasively and to relate it to the underlying fiber structure of the myocardium. This objective is motivated by the fact that cardiac excitation and arrhythmogenesis involve the three-dimensional ventricular wall and its anisotropic structure.

QT interval dispersion: dispersion of ventricular repolarization or dispersion of QT interval?

The QT interval (QTI) has long been useful as a clinical index of the duration of ventricular repolarization, particularly as a marker of prolonged repolarization and its well-established association with arrhythmogenic cardiac states. Likewise, inhomogeneity (dispersion) of repolarization has been linked definitively to increased susceptibility to reentrant arrhythmias. Recent studies have reported the use of QTI dispersion as a meaningful clinical index to identify patients at risk, but the interpretation of the measurement has been controversial.

Noninvasive electrocardiographic imaging: reconstruction of epicardial potentials, electrograms, and isochrones and localization of single and multiple electrocardiac events.

Background: The goal of noninvasive electrocardiographic imaging (ECGI) is to determine electric activity of the heart by reconstructing maps of epicardial potentials, excitation times (isochrones), and electrograms from data measured on the body surface.

Methods And Results: Local electrocardiac events were initiated by pacing a dog heart in a human torso-shaped tank. Body surface potential measurements (384 electrodes) were used to compute epicardial potentials noninvasively.

Noncontact endocardial mapping: reconstruction of electrograms and isochrones from intracavitary probe potentials.

Introduction: Mapping endocardial activation and repolarization processes is critical to the study of arrhythmias and selection of therapeutic procedures. Previously, we developed methodology for reconstructing endocardial potentials from potentials measured with a noncontact, intracavitary probe. This study further develops and evaluates the ability of the approach to provide detailed information on the spatiotemporal characteristics of the activation process.