Bibliothek

Notizen: Reentrant Activity in Cardiac Tissue. This review article summarizes theoretical insights into the principles and mechanisms associated with reentrant activity in cardiac tissue. A mathematical ring model is used in computer simulations to investigate, at the cellular level, mechanistic aspects of initiation, perpetuation, and termination of reentry. Taking advantage of the ability to compute membrane processes in this model, we relate dynamic properties of the reentrant action potential (e.g., beat-to-beat alternans) to the underlying kinetics of membrane ionic channels. Effects on reentry of inhomogeneities in refractoriness, excitability, cellular coupling at gap junctions, and fiber cross-section are also studied.

Notizen: Vulnerable Window of Unidirectional Block. Introduction: Unidirectional block is a requisite event in the initiation of reentry in cardiac tissue, but its initiation and behavior in the presence of tissue pathologies remain poorly understood. Previous experimental and theoretical reports on vulnerability to unidirectional block under conditions of reduced cellular coupling and reduced membrane excitability have varied due to differences in experimental and simulation protocols. Methods and Results: We have addressed the issue of vulnerability to unidirectional block using the recent Luo-Rudy membrane model and computer simulations of propagation in a one-dimensional cardiac fiber. The vulnerable window (VW) of unidirectional block from premature stimulation is expressed in units of time, VWtime, and as a range of membrane potentials at the stimulus site, VWpot VWpot and VWtime, were quantified over a range of membrane excitability and gap junction resistances (intercellular coupling). With normal membrane excitability and intercellular coupling, VWpot, and VWtime, were small (VWPot, = 0.44 mV, VWtime, = 0.39 msec). A uniform reduction (0.25 ×) in the degree of intercellular coupling increased VWtime, and VWpot, by factors of 3.6 and 4.7, respectively, whereas a uniform decrease (0.25 ×) in membrane excitability (same resulting velocity) increased VWtime, by only a factor of 0.4 and decreased VWpot, to negligible levels. When inhomogeneities in fiber properties were introduced (intercellular coupling and membrane excitability), VWtime, increased more due to inhomogeneity in membrane excitability (VWtime= 4.5 msec) than to inhomogeneity in intercellular coupling (VWtime, = 1.5 msec). The simulations also clarify the dependence of the VW on the dimensions of the stimulating electrode. The length of the stimulating electrode added a factor, equal to the propagation time across the eiectrode length, to the intrinsic VW of the fiber. Conclusions: VWpot, and VWtime, are both important parameters for quantifying vulnerability to unidirectional block. In an environment with uniform distribution of fiber and membrane properties, reduced intercellular coupling bas a greater effect on the VW than reduced membrane excitability. Inhomogeneous reduction of membrane excitability can significantly enhance vulnerability to unidirectional block, much more so than inhomogeneous reduction of intercellular coupling. Theoretically, stimulation at a point should be used to define the VW. Finite electrode dimensions introduce a geometrical factor that affects the measurement of the VW.

Notizen: Effect of Inhomogeneities on Body Surface. Introduction: Body surface potential maps (BSPMs) and conventional ECG reflect electrical sources generated by cardiac excitation and repolarization and noninvasively provide important diagnostic information about the electrical state of the heart. Because the heart is located within the torso volume conductor, body surface potentials also reflect the effects of torso inhomogeneities, which include blood, lungs, bone, muscle, fat, and fluid. It is necessary to characterize and understand these effects in order to interpret BSPM and ECG in terms of cardiac activity without “contamination” from the inhomogeneous volume conductor. Methods and Results: Actual measured epicardial and body surface potentials were obtained during normal sinus rhythm and for different pacing protocols from a Langendorff-perfused dog heart suspended in a human-shaped torso tank. Accurate geometry of the torso inhomogeneities was digitized from the Visual Human Project and appropriately introduced into a computer model of the tank setup. The geometry and electrical properties of the volume conductor could be varied. Both homogeneous and inhomogeneous torsos have major smoothing effects on BSPM, which is of very low resolution compared with its corresponding epicardial potential pattern. Relative to a homogeneous torso, the inhomogeneities have only a minor effect on BSPM patterns. They augment potential magnitudes depending on the pattern of epicardial activation. Variations of geometry and electrical properties within the normal physiologic range have minimal effects. Conclusion: Effects of torso inhomogeneities on 12-lead ECGs are minimal, and the associated ECG changes fall within the range of normal interindividual variations.

Notizen: The complex discontinuous architecture of cardiac tissue induces a number of interactions between the cellular properties of the myocardium that affect impulse propagation:1. Slow (〈 10 cm/sec) conduction velocities in the myocardium can only be achieved by discontinuous conduction. In the more continuous type of conduction, as occurring during inhibition of INa, conduction block occurs at velocities of approximately 20 cm/sec.2. If the discontinuity reaches a critical degree, Ica, L is needed to propagate the cardiac impulse. This situation may occur during cell-to-cell uncoupling and at sites of local tissue discontinuities.3. The conduction phenomena occurring at tissue discontinuities, such as pivoting points, isthmus, and abrupt tissue expansions are markedly influenced by the underlying properties of the cellular network. Electrical uncoupling at the cellular level can reduce the effect of the discontinuities to produce conduction block and reverse unidirectional block to bidirectional conduction. By contrast, reduction of INa increases the probability of unidirectional block at such sites. Since activation of INa may become rate-dependent at high rates and in depolarized tissue, this predicts an instability in activation patterns during a tachycardia.Do the above considerations really predict arrhythmogensis? It is obvious that increasing the degree of structural discontinuity creates a substrate for reentrant arrhythmias. However, with the exception of the demonstration of spiral wave initation in vitro,5 no direct effects of tissue discontinuities on arrhythmia initiation have been demonstrated so far. Furthermore, pathologies associated with an increased degree of structural discontinuities, such as a hypertrophy and failure, also show an increased propensity to triggered arrhythmias, and initiation of ventricular tachcardias from small foci has been observed in whole hearts. These complexities make it difficult to extrapolate findings of experimental and theoretical work at the cellular level directly to whole hearts and human pathologies where several mechanisms for initiation and maintenance of tachycardias may coexist.

Notizen: Background:Cardiac arrhythmias continue to be a leading cause of death and disability. Despite this alarming fact, a noninvasive imaging modality for cardiac electrophysiology (EP) has not been developed. Standard electrocardiographic techniques attempt to infer electrophysiological processes in the heart from a limited number of recordings on the body surface. This traditional approach is limited in its ability to provide information on regional electrocardiac activity and to localize electrophysiological events in the heart (e.g., arrhythmogenic foci; regions of elevated dispersion of myocardial repolarization). This article reviews the development of a novel imaging modality (electrocardiographic imaging [ECGI]) for the reconstruction of cardiac electrical activity from potentials measured away from the heart (i.e., on the torso surface). The results presented demonstrate that ECGI can noninvasively reconstruct epicardial potentials, electrograms, and isochrones with good accuracy and resolution. Results:The locations of ectopic pacing sites are reconstructed within 10 mm of their actual positions. Dual epicardial pacing sites separated by 52 mm, 35 mm, and 17 mm can be resolved. The depth of intramural ectopic activity can be estimated and the direction of intramural activation spread can be determined from the reconstructed epicardial potential pattern and its evolution in time. Results from infarcted hearts demonstrate that ECGI can detect and reconstruct the abnormal electrophysiological substrate associated with the infarct. The figure-of-eight pattern of reentrant activation in the epicardial border zone during ventricular tachycardia is also reconstructed by ECGI noninvasively. Conclusions:These results demonstrate the potential of ECGI as a clinical noninvasive imaging modality for identifying patients at risk of cardiac arrhythmias and for guiding and evaluating antiarrhythmic interventions in such patients. A.N.E. 1999;4(3):340–359

Notizen: Noncontact Mapping of Arrhythmogenic Substrates. Introduction: In previous studies, we established methodology for reconstructing endocardial potential maps, electrograms, and isochrones from a noncontact intracavitary catheter during a single beat. Recently, we evaluated this approach using a 9-French (3-mm) spiral catheter in a normal heart preparation. Here we extend the approach to hearts with structural disease and examine its ability to detect and characterize abnormal electrophysiologic (EP) substrates and to map ventricular arrhythmias on a beat-by-beat basis. Methods and Results: Reconstruction of endocardial potentials from cavity potentials measured with 82 electrodes mounted on a 9-French spiral catheter was performed in an isolated canine left ventricle (LV). Endocardial potentials were recorded with 91 intramural needles, providing a gold standard for evaluating the noncontact reconstruction. Studies were performed in a normal LV (control) and the same LV 3 hours after left anterior descending coronary artery occlusion and ethanol injection to create an infarct. Abnormal EP characteristics over the infarct were faithfully reconstructed, including (1) low potentials and electrogram derivatives; (2) fractionated electrograms; (3) small deflections on electrograms reflecting local activation; and (4) slow discontinuous conduction transverse to fibers. During arrhythmia, beat-to-beat dynamic shifts of initiation site and activation pattern were captured by the reconstruction. Conclusion: Noncontact, nonexpendable catheter mapping can locate and characterize abnormal EP substrates and can capture the endocardial sequence of an arrhythmia during a single beat.

Notizen: Noncontact Endocardial Mapping. 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. Specifically, we reconstructed endocardial electrograms and isochrones throughout the activation process over the entire endocardium during a single beat. Methods and Results: Cavity potentials were measured with a 65-electrode probe placed inside an isolated canine left ventricle. Endocardial potentials were measured simultaneously using 52 electrodes. Potentials were acquired during subendocardial pacing from different locations. Computed electrograms at various sites closely resemble the measured electrograms (correlation coefficient 〉 0.9 at 60% of the electrodes). Computed isochrones locate subendocardial pacing sites with 10-mm accuracy. Two pacing sites, 17 mm apart, were resolved. Critical regions, such as areas of isochrone crowding, were accurately reconstructed. Conclusions: Results indicate the applicability of the approach to mapping the cardiac excitation process on a beat-by-beat basis without occluding the ventricle. The ability of locating electrical events (e.g., single or multiple initiation sites) is demonstrated. Importantly, the method is shown to be capable of reconstructing electrograms over the entire endocardium and determining nonuniformities of activation spread (e.g., areas of slow conduction). These capabilities are important to clinical application in the electrophysiology laboratory and experimental studies of arrhythmias in the intact animal.