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Biomedical subjects

R L Lux

Publications and source records attributed to R L Lux.

At least 19 recordsLinked to original sources
PubMed1998

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. METHODS AND RESULTS: Intramural activation was initiated by pacing a dog heart in a human torso tank. Body surface potentials (384 electrodes) were used to compute epicardial potentials noninvasively. Accuracy of reconstructed epicardial potentials was evaluated by direct comparison to measured ones (134 electrodes). Protocols included pacing from five intramural depths. Epicardial potentials showed characteristic patterns (1) early in activation, central negative region with two flanking maxima aligned with the orientation of fibers at the depth of pacing; (2) counterclockwise rotation of positive potentials with time for epicardial pacing, clockwise rotation for subendocardial pacing, and dual rotation for midmyocardial pacing; and (3) central positive region for endocardial pacing. Noninvasively reconstructed potentials closely approximated these patterns. Reconstructed epicardial electrograms and epicardial breakthrough times closely resembled measured ones, demonstrating progressively later epicardial activation with deeper pacing. CONCLUSIONS: ECGI can noninvasively estimate the depth of intramyocardial electrophysiological events and provides information on the spread of excitation in the three-dimensional anisotropic myocardium on a beat-by-beat basis.

Animals↗
PubMed1998

A possible mechanism for electrocardiographically silent changes in cardiac repolarization.

Despite the widespread use of electrocardiogram (ECG), changes in cardiac activity resulting from ischemia or altered recovery characteristics sometimes remain electrocardiographically "silent" or are first detectable by techniques that measure ventricular contractility, such as ultrasound or blood pressure. Especially local changes in repolarization can go undetected when ECG electrodes do not lie close to the area of the heart affected. Experiments were performed on an isolated, perfused canine heart suspended in a realistically shaped, instrumented, electrolytic torso tank with the goal of determining some mechanisms for these ambiguities. By recording simultaneously both epicardial and torso tank surface potentials, complete descriptions were obtained of the electrical response to interventions such as coronary occlusions and alterations in pacing site and frequency. One hypothesis was that some interventions produce highly variable ECG responses primarily because of differences in their location within the heart. To test this, the effect was measured of repeating the same intervention as the heart's location and orientation in the tank were varied. A numerical forward solution was also used to investigate variation of torso tank potentials with heart location. The resulting changes in tank surface potentials illustrate how, for example, precordial ST-segment shifts following occlusion change from elevation to depression to become almost undetectable as the heart rotates in the tank. The results suggest that some events are electrocardiographically silent because of the complex geometric relationship of the heart, torso, and site of the lesion, as well as the spatial sampling and analysis techniques used in detection.

Animals↗
PubMed1998

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. A Langendorff-perfused, isolated canine heart suspended in a torso-shaped, electrolytic tank filled with NaCl-sucrose solution was used to investigate the relationship between body surface QTIs and ventricular repolarization measured directly from the cardiac surface by using activation-recovery intervals, which have been documented to reflect the duration of local action potentials as well as local refractory periods. The data showed poor correlation between cardiac surface activation-recovery intervals and QTIs, as well as the insensitivity of QTIs to regional repolarization shortening in the presence of prolonged repolarization elsewhere. Furthermore, the data confirmed that torso tank QTI dispersion does not reflect directly the full range of measured ventricular repolarization inhomogeneity. It is concluded that body surface QTI dispersion is not a reliable index of repolarization dispersion.

Action Potentials↗
PubMed1998

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. Despite these advantages, body surface mapping has not become a routinely used clinical method. One reason is that visual examination and sophisticated analysis of BSMs do not permit inferring the sequence of excitation and repolarization in the heart with a sufficient degree of certainty and detail. These limitations can be partially overcome by implementing inverse procedures that reconstruct epicardial potentials, isochrones, and ECGs from body surface measurements. Furthermore, ongoing experimental work and simulation studies show that a great deal of information about intramural events can be elicited from measured or reconstructed epicardial potential distributions. Interpreting epicardial data in terms of deep activity requires extensive knowledge of the architecture of myocardial fibers, their anisotropic properties, and the role of rotational anisotropy in affecting propagation and the associated potential fields.

Body Surface Potential Mapping↗
PubMed1998

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. Potential distributions and waveforms were recorded from saline solutions and rat heart epicardium during ventricular paced beats and during passive current injection in the diastolic interval. Electrical responses obtained from rat epicardium compared favorably with those observed in studies of larger-animal hearts, which used arrays having greater electrode spacing, and revealed the effects of myocardial anisotropy. Epicardial potentials measured early after stimulation in the region surrounding the pacing site were interpreted in terms of potentials generated by an equivalent quadrupolar source. We conclude that electrode arrays for epicardial mapping of small hearts can be constructed with sufficient ease and precision to allow detailed study of fiber structure and electrophysiology in these hearts in normal and pathological conditions.

Action Potentials↗
PubMed1997

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. The accuracy of reconstructed epicardial potentials was evaluated by direct comparison to measured ones (134 electrodes). Protocols included pacing from single sites and simultaneously from two sites with various intersite distances. Body surface potentials showed a single minimum for both single- and double-site pacing (intersite distances of 52, 35, and 17 mm). Noninvasively reconstructed epicardial electrograms, potentials, and isochrones closely approximated the measured ones. Single pacing sites were reconstructed to within < or = 10 mm of their measured positions. Dual sites were located accurately and resolved for the above intersite distances. Regions of sparse and crowded isochrones, indicating spatial nonuniformities of epicardial activation spread, were also reconstructed. CONCLUSIONS: The study demonstrates that ECGI can reconstruct epicardial potentials, electrograms, and isochrones over the entire epicardial surface during the cardiac cycle. It can provide detailed information on local activation of the heart noninvasively. Its uses could include localization of cardiac electric events (eg, ectopic foci), characterization of nonuniformities of conduction, characterization of repolarization properties (eg, dispersion), and mapping of dynamically changing arrhythmias (eg, polymorphic VT) on a beat-by-beat basis.

Animals↗
PubMed1997

Effects of heart rate on vulnerability to fibrillation in a computer model.

Effects of heart rate on refractory period (RP) duration and disparity have opposing actions on vulnerability to fibrillation. Both bradycardia and tachycardia have been reported to increase vulnerability to fibrillation, and the role of their effects on RP duration and disparity in producing that effect is uncertain. That role has been investigated with a computer model of propagated excitation having nonuniform, cycle length-dependent refractoriness and slow propagation during incomplete recovery of excitability. Vulnerability was assessed as fibrillation threshold (FT), defined as the duration of train stimulation required to initiate simulated fibrillation. When measured as a function of train onset time during a cycle, FT initially decreased to a minimum and then increased to the original level. Slower rates shifted that curve upward and to the right, so that the FT was higher during early portions of the cycle but lower in later portions. Longer mean duration of RPs increased FT during all portions of the cycle, increased the difference of FT at various rates during early portions of the cycle, and decreased differences later in the cycle. Greater RP range reduced the FT and decreased the difference of FT with varied rate in early portions of the cycle, while increasing the difference in later portions. Accelerating rate had additional effects on FT-related to nonuniform propagation of responses prior to train stimulation. The findings defined mechanisms based on established effects of rate on RP, by which either tachycardia or bradycardia could increase vulnerability to fibrillation, and demonstrated the effects of RP range and duration on the mechanisms.

Atrial Fibrillation↗
PubMed1997

Mechanisms in adrenergic dependent onset of torsades de pointes.

Pause dependent onset of torsades de pointes is characteristic in acquired long QT syndromes, and the probable mechanism is reentry facilitated by increased disparity of refractoriness following a long cycle. Adrenergic dependent onset is usual in familial long QT syndromes, and the mechanism is uncertain. In this study with a computer simulation of torsades de pointes, possible mechanisms of adrenergic dependent onset have been identified. Decreased refractory periods facilitated the initiation of torsades de pointes by permitting earlier premature excitation and allowing reentry in the presence of the shorter refractory period that had been further shortened by the earlier excitation. In addition, accelerating rate resulted in responses occurring in the presence of refractory periods set by the prior response so each response was premature with respect to the preceding one. The difference between cycle lengths and refractory period decreased with increasing rate leading to the functional block required for initiation of simulated torsades de pointes. Findings define possible mechanisms by which the adrenergic effects of reduced refractory period duration and increased rate may lead to the initiation of torsades de pointes.

Adrenergic Fibers↗
PubMed1997

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. 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.

Animals↗
PubMed1997

Three-dimensional distribution of ST-T wave alternans during acute ischemia.

INTRODUCTION: A canine model of reversible ischemia was used to measure the magnitude and transmural distribution of repolarization alternans. METHODS AND RESULTS: Twenty-four multielectrode needles were inserted into a reversibly ischemic region created by 8 minutes of coronary occlusion. One hundred ninety-two unipolar electrograms were simultaneously recorded at 1-minute intervals for 8 minutes of ischemia and 3 minutes of reflow recovery. Beat-to-beat repolarization alternans was quantified for all electrograms using the standard deviation of QRST integrals. When alternans from animals that fibrillated was compared with alternans from animals that did not, the magnitude of alternans in the fibrillation group was an average standard deviation of 1125 +/- 99.7 mV-msec at the time of fibrillation and 409 +/- 183 mV-msec at 8 minutes of ischemia in the animals that did not fibrillate. The increase in alternans occurred mainly in the mid-myocardial and epicardial regions in the animals that fibrillated. QRS morphology of sequential electrograms did not differ in beat-to-beat comparison, suggesting that repolarization alternans measured was not due to alternating conduction block in the region of reversible ischemia. CONCLUSION: During acute ischemia, the magnitude and distribution of repolarization alternans are greater and differ in hearts that experience ventricular fibrillation. This observation may have clinical utility in arrhythmia prediction. It also is consistent with the possibility there may be multiple mechanisms for repolarization alternans.

Animals↗
PubMed1997

Anatomical architecture and electrical activity of the heart.

In most early studies of cardiac electrophysiology, the correlation between propagation of excitation and the architecture of cardiac fibers was not addressed. More recently, it has become apparent that the spread of excitation, the sequence of recovery, the associated time-varying potential distributions and the intra- and extracardiac electrocardiograms are strongly affected by the complex orientation of myocardial fibers. This article is a review of older and very recent, partly unpublished, mathematical simulations and experimental findings that document the relationships between cardiac electrophysiology and fiber structure. Important anatomical factors that affect propagation and recovery are: the elongated shape of myocardial fibers which is the basis for electrical anisotropy; the epi-endocardial rotation of fiber direction in the ventricular walls; the epi-endocardial obliqueness of the fibers ("imbrication angle"), and the conduction system. Due to the complex architecture of the fibers, many different pathways are available to an excitation wavefront as it spreads from a pacing site: the straight line; the multiple, bent pathways resulting from the epi-endocardial rotation of fiber direction; the coiling intramural pathways associated with the "imbrication" angles (Streeter) and the pathways involving the Purkinje network. Only in a few cases is the straight line the fastest pathway. The shape of an excitation wavefront at a given time instant results from the competition between all possible pathways. To compute the potential distributions and ECG waveforms generated by a spreading excitation wave we must know the successive shapes and positions of the wavefront, the architecture of the fibers through which it propagates and the spatial distribution of their anisotropic electrical properties.

Electrophysiology↗
PubMed1996

Genetically defined therapy of inherited long-QT syndrome. Correction of abnormal repolarization by potassium.

BACKGROUND: Many members of families with inherited long-QT (LQT) syndrome have mutations in HERG, a gene encoding a cardiac potassium channel that is modulated by extracellular potassium. We hypothesized that an increase in serum potassium would normalize repolarization in these patients. METHODS AND RESULTS: We studied seven subjects with chromosome 7-linked LQT syndrome and five normal control subjects. Repolarization was measured by ECG and body surface potential mapping during sinus rhythm, exercise, and atrial pacing, before and after serum potassium increase. Potassium administration improved repolarization in the LQT syndrome. At baseline, LQT subjects differed from control subjects: resting corrected QT interval (QTc, 627 +/- 90 versus 425 +/- 25 ms, P = .0007), QTc dispersion (133 +/- 62 versus 36 +/- 9 ms, P = .009), QT/RR slope (0.35 +/- 0.08 versus 0.24 +/- 0.07, P = .04), and global root-mean-square QT interval (RMS-QTc; 525 +/- 68 versus 393 +/- 22, P = .002). All LQT subjects had biphasic or notched T waves. After administration of potassium, the LQT group had a 24% reduction in resting QTc interval (from 617 +/- 92 to 469 +/- 23 ms, P = .004) compared with a 4% reduction among control subjects (from 425 +/- 25 to 410 +/- 45 ms, P > .05). The reduction was significantly greater in LQT subjects (P = .018). QT dispersion became normal in LQT subjects and did not change in control subjects. The slope of the relation between QT interval and cycle length (QT/RR slope) decreased toward normal. T-wave morphology improved in six of seven LQT subjects. The LQT group had a greater reduction in RMS-QTc than control subjects (P = .04). CONCLUSIONS: An increase in serum potassium corrects abnormalities of repolarization duration, T-wave morphology, QT/ RR slope, and QT dispersion in patients with chromosome 7-linked LQT.

Adult↗
PubMed1996

Measuring spatial waves of repolarization in canine ventricles using high-resolution epicardial mapping.

The importance of the role of ventricular repolarization in arrhythmogenesis and defibrillation prompted the exploration of new methods for observing and measuring repolarization. Specifically, the authors' goal was to establish independent procedures for assessing activation-recovery intervals. Canine epicardial electrograms from high-resolution arrays (2-mm spacing, 25 x 21 electrodes) were recorded-during pacing from a variety of single or simultaneously paced epicardial locations in canine hearts. For each activation sequence, the activation and repolarization times were measured using timing of intrinsic QRS and T wave deflections (activation-recovery interval method) and timing of the peak magnitude of spatial derivatives (gradient method). Both methods should, theoretically, provide estimates of local activation and repolarization times, which reflect timing of local action potential upstrokes and downstrokes. Scattergrams comparing activation and recovery times for the two methods showed high correlation, slopes close to 1.0, and intercepts near the origin. For most activation sequences, observation of the potential and gradient distributions as dynamic, three-dimensional perspective displays, revealed a well-defined, rapidly propagating repolarization wave, superimposed on a slowly varying, high-amplitude distribution occurring during the T wave. These data suggest that repolarization times measured using temporal or spatial derivatives are consistent with theoretical predictions and reflect timing of local action potential downstrokes. They also suggest potential utility of combining spatial and temporal approaches for improving reliability in the measurements.

Action Potentials↗
PubMed1996

Evaluation of novel measurement methods for detecting heterogeneous repolarization.

There exists a well-documented link between heterogeneity of cardiac recovery characteristics and vulnerability to arrhythmia; however, electrocardiographic detection of this heterogeneity remains problematic. The only modalities suitable for measuring variation of repolarization are electrophysiologic in nature, with action potential duration in single cells the most direct method and QT intervals from the body surface electrocardiogram the most common clinical approach. The authors have shown previously, however, that the QT interval is a poor measure of regional change in repolarization, especially when shortening occurs. Here, the authors discuss an experimental preparation based on an isolated canine heart suspended in a human-shaped, instrumented, electrolytic tank and describe a method of applying cold to create local, transient changes in recovery characteristics. The authors have simultaneously recorded epicardial and torso tank surface potentials before, during, and after intervention, and from them have generated isopotential and isointegral maps and computed activation-recovery intervals (ARIs). In all cases, epicardial potentials revealed changes in recovery associated with localized heating and cooling. The changes were visible from tank surface potential distributions in some, but not all, cases. The results also suggest that epicardial ARIs are sensitive to changes in recovery and that, at least for a subset of tank surface leads, ARIs can be used to create noninvasive indices of disparity of repolarization characteristics.

Animals↗
PubMed1996

Effects of premature responses on vulnerability to fibrillation in a computer model.

The purpose of this study was to determine the effects of premature responses on vulnerability to fibrillation using a computer model based on the wavelet hypothesis. The model simulated propagation, nonuniform recovery of excitability, and slow propagation during incomplete recovery. Vulnerability was assessed as the fibrillation threshold, which was defined as the duration of train stimulation required to initiate self-sustained reentrant excitation with multiple excitation fronts. The fibrillation threshold was determined at various premature cycle lengths in the presence of refractory periods of varied range and duration, at various rates, and after compensatory pauses and varied patterns of consecutive premature responses. The fibrillation threshold was found to be reduced by premature responses, and with increasing premature cycle length, there was an initial decrease followed by an increase of fibrillation threshold. The fibrillation threshold was directly related to the duration and indirectly related to the range of the refractory period. The time phase of curves relating premature cycle length and fibrillation threshold was such that premature responses at some cycle lengths were associated with a lower fibrillation threshold in the presence of longer refractory periods, with slower rates, and with an immediately preceding compensatory pause. The mechanism may be important in the proarrhythmia effects of drugs that prolong repolarization and in the bradycardia-tachycardia syndrome. Consecutive premature responses at a constant rate increased the fibrillation threshold in comparison with the initial response, while consecutive responses at an accelerating rate decreased the fibrillation threshold.

Atrial Fibrillation↗
PubMed1995

Reconstruction of endocardial potentials and activation sequences from intracavitary probe measurements. Localization of pacing sites and effects of myocardial structure.

BACKGROUND: Mapping of endocardial activation is an important procedure for diagnosing cardiac arrhythmias and locating the arrhythmogenic site before treatment. The objective of the present study was to develop and test a mathematical method to reconstruct the endocardial potentials and activation sequences (isochrones) from potential data measured with a noncontact, intracavitary multielectrode probe (the "inverse problem"). METHODS AND RESULTS: A boundary element based mathematical method, combined with a numeric regularization technique, was developed for computing the inverse solution. Endocardial potentials were computed from intracavitary potentials measured with a multielectrode probe placed in the cavity of an isolated, perfused canine left ventricle. Data were acquired during rhythms induced by electrical stimuli applied at different locations and varying depths within the myocardium. Endocardial potentials were measured using intramural needles to evaluate the accuracy of the inverse solutions by direct comparison. Inversely computed endocardial potentials, from measured probe potentials, reconstruct with good accuracy the major features (potential maxima and minima, regions of negative and positive potentials) compared with the measured endocardial potentials. During early activation, the computed endocardial potentials exhibit a potential minimum in close proximity to the pacing site, determining the location of the stimulus with good accuracy (within 10-mm error). Multiple stimuli, as close as 10 to 20 mm to each other, can be distinguished and localized to their sites of origin by the inverse reconstruction. Similar to the measured endocardial potentials, the spatial distribution of the computed endocardial potentials reflects the underlying cardiac fiber direction, and dynamic changes of the computed endocardial potentials reflect the rotation of fibers with intramural depth. Maps of isochrones show good correspondence between the isochrones determined from the computed endocardial potentials and those determined directly from the measured endocardial potentials. CONCLUSIONS: Compared with actual, measured endocardial potentials and activation sequences, endocardial potential patterns and activation sequences can be reconstructed on a beat-by-beat basis from cavitary potentials measured with a multielectrode, noncontact probe. The approach presented here is shown to reconstruct, with 10-mm accuracy and resolution of 10 to 20 mm, local events of cardiac excitation (eg, pacing sites). In addition, the reconstructed endocardial potentials correctly reflect the underlying fibrous structure of the myocardium. These results demonstrate the feasibility of the approach. In the experiments, the probe position and endocardial geometry were determined invasively. To be clinically applicable, the reconstruction method should be combined with a noninvasive method for determining the probe-cavity geometry in the catheterization laboratory. It could then be developed into a catheter-based technique for locating arrhythmogenic sites and for studying and diagnosing conduction abnormalities, reentrant activity, and the effects of drugs and other interventions on cardiac activation and arrhythmias.

Animals↗