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Y Rudy

Publications and source records attributed to Y Rudy.

At least 73 records · Page 4Linked to original sources
PubMed1994

A dynamic model of the cardiac ventricular action potential. II. Afterdepolarizations, triggered activity, and potentiation.

The action potential model presented in our accompanying article in this journal is used to investigate phenomena that involve dynamic changes of [Ca2+]i, as described below. Delayed afterdepolarizations (DADs) are induced by spontaneous Ca2+ release from the sarcoplasmic reticulum (SR), which, in turn, activates both the Na(+)-Ca2+ exchanger (INaCa) and a nonspecific Ca(2+)-activated current (Ins(Ca)). The relative contributions of INaCa and of Ins(Ca) to the generation of DADs are different under different degrees of Ca2+ overload. Early afterdepolarizations (EADs) can be categorized into two types: (1) plateau EADs, resulting from a secondary activation of the L-type Ca2+ current during the plateau of an action potential, and (2) phase-3 EADs, resulting from activation of INaCa and Ins(Ca) by increased [Ca2+]i due to spontaneous Ca2+ release from the SR during the late repolarization phase. Spontaneous rhythmic activity and triggered activity are caused by spontaneous Ca2+ release from the SR under conditions of Ca2+ overload. Postextrasystolic potentiation reflects the time delay associated with translocation of Ca2+ from network SR to junctional SR. The cell is paced at high frequencies to investigate the long-term effects on the intracellular ionic concentrations.

Action Potentials↗
PubMed1994

Voltage-independent effects of extracellular K+ on the Na+ current and phase 0 of the action potential in isolated cardiac myocytes.

A rise in [K+]o, by depolarizing the resting membrane potential and partially inactivating the inward Na+ current (INa), is believed to play a critical role in slowing conduction during myocardial ischemia. In multicellular ventricular preparations, elevation of [K+]o has been suggested to decrease Vmax to a greater extent than expected from membrane depolarization alone. The mechanism of this voltage-independent effect of [K+]o is currently unknown, and its significance in single cardiac cells has not been determined. We have examined the voltage-independent effects of elevated [K+]o on INa and the action potential upstroke in isolated rabbit atrial and ventricular myocytes under voltage- and current-clamp conditions. Superfusate [K+] was varied from 5 mmol/L to 14 or 24 mmol/L, whereas [Na+] was maintained at 150 mmol/L. In cultured atrial cells and excised outside-out patches from freshly isolated atrial and ventricular cells, the amplitude and kinetics of INa were unchanged by elevation of [K+]o. In atrial cells, action potentials elicited from a holding potential of -70 mV had a similar Vmax (114.9 +/- 5.7 versus 112.2 +/- 4.8 V/s, mean +/- SEM, n = 6) and action potential amplitude (115.0 +/- 2.4 versus 113.4 +/- 3.9 mV) in 5 and 24 mmol/L [K+]o. In contrast, in ventricular cells at a holding potential of -70 mV, increasing [K+]o fro 5 to 14 mmol/L decreased Vmax from 161.8 +/- 18.0 to 55.3 +/- 5.0 V/s (n = 7, P < .001) and action potential amplitude from 128.1 +/- 1.3 to 86.6 +/- 5.4 mV (P < .001). This voltage-independent decrease in Vmax and action potential amplitude induced by elevated [K+]o was abolished in the presence of 1 mmol/L Ba2+, suggesting that it is attributable to an increased background K+ conductance. We conclude that elevation of [K+]o to levels expected during ischemia causes a marked voltage-independent depression of Vmax in ventricular cells, which may, in turn, contribute to the slowing of myocardial conduction characteristic of early ischemia.

Action Potentials↗
PubMed1993

Cellular responses to electrical stimulation: a study using a model of the ventricular cardiac action potential.

A mathematical model of the membrane action potential of a ventricular cardiac cell is used to examine the cellular responses to premature stimulation. Results demonstrate the importance of the slow recovery of INa in determining the response of the cell. Simulated responses to periodic stimulation include monotonic Wenckebach patterns and alternans in APD at normal [K]O. At low [K]O, nonmonotonic Wenckebach periodicities, aperiodic patterns, and enhanced supernormal excitability that results in unstable responses ("chaotic activity") are observed. These observations are consistent with recent experimental results, and the simulations provide insights into the underlying mechanisms at the level of membrane ionic channel kinetics.

Action Potentials↗
PubMed1993

ECG body surface potential mapping many years after successful surgery for coarctation of the aorta.

Patients with coarctation of the aorta (CoA) who previously underwent successful surgery are often diagnosed on standard electrocardiograms as having partial right bundle branch block. After surgery 24 patients with CoA had body surface potential mapping (BSPM) with the Case Western Reserve University 180 electrode system; of these 7 had additional aortic stenosis and none had ever had intracardiac communication. The average age at the initial surgery for CoA was 4.0 +/- 3.3 years and at the time of the BSPM it was 12.7 +/- 5.9 years. For the 17 patients with CoA without aortic stenosis the average age at the initial surgery was 5.0 +/- 3.4 years and at the time of the BSPM it was 14.2 +/- 6.0 years. In 11 of the 24 patients, a cardiac catheterization was performed, and each patient demonstrated normal pulmonary artery and right ventricular systolic pressure except for one child with 40 mmHg systolic. In the others all indications were that right ventricular pressure was normal. In 11 of the 24 patients, congestive heart failure had been present in infancy. All 24 cases had evidence for epicardial right ventricular breakthrough on the BSPM, a finding believed to indicate right ventricular activation from endocardium to epicardium via the normal Purkinje system. There were no findings on the BSPM suggesting that right bundle branch block was present. Right ventricular hypertrophy with or without terminal right conduction delay was present on the BSPM in 19 of the 24 patients (9 with additional left ventricular hypertrophy--left ventricular hypertrophy alone in 5). Right ventricular hypertrophy could be considered in 6 of 19 patients in the electrocardiogram, and in 11 of 19 in the vectorcardiogram. The mechanism for the persistent electrocardiographic right ventricular hypertrophy is postulated to involve right ventricular hyperplasia in utero or in early neonatal life, which never disappears.

Adolescent↗
PubMed1993

Characterization of double potentials in a functionally determined reentrant circuit. Multiplexing studies during interruption of atrial flutter in the canine pericarditis model.

OBJECTIVES: We tested the hypothesis that double potentials recorded during atrial flutter in a functionally determined reentrant circuit reflect activation of the reentrant wave front around an area of functional conduction block. BACKGROUND: The center of the atrial flutter reentrant circuit in the sterile pericarditis canine model is characterized by double potentials. METHODS: We studied 11 episodes of atrial flutter in eight dogs during interruption of atrial flutter while pacing the atria. A multielectrode mapping system was used to record simultaneously from 190 electrodes on the right atrium (location of reentry). RESULTS: Interruption of atrial flutter occurred when the orthodromic wave front from the pacing impulse blocked in an area of slow conduction in the reentrant circuit. The response of the double potential with interruption of atrial flutter depended on the location of the recording site relative to this area of block. Two types of response were seen. When the double potential was recorded orthodromically distal to this area of block, interruption of atrial flutter was associated with disappearance of the second deflection, and continued pacing after interruption of atrial flutter was not associated with reappearance of the second potential. When the double potential was recorded at a site orthodromically proximal to the area of block, interruption of atrial flutter was not associated with disappearance of the second potential, and when rapid atrial pacing was continued, the double potential remained despite disappearance of the atrial flutter reentrant circuit. CONCLUSIONS: Double potentials represent functional conduction block in the center of the reentrant circuit, with each deflection of the double potential reflecting activation on either side of the area of functional block. The data also demonstrate that double potentials are not limited to a reentrant circuit, as they were recorded on either side of an area of block in the absence of such a circuit.

Action Potentials↗
PubMed1993

Mechanism of spontaneous termination of stable atrial flutter in the canine sterile pericarditis model.

BACKGROUND: We tested the hypotheses that spontaneous termination of stable atrial flutter is directly related to spontaneous beat-to-beat cycle length oscillations and that block of the circulating reentrant wave front occurs in an area of slow conduction. METHODS AND RESULTS: We studied 30 episodes of spontaneous termination of stable atrial flutter induced by atrial stimulation in 11 conscious, nonsedated dogs with sterile pericarditis. Additionally, in 5 dogs, 14 episodes of spontaneous termination of stable atrial flutter were studied with a multisite mapping system to record simultaneously from 190 right atrial electrodes. In the conscious-state studies, atrial flutter cycle length oscillations began 6 +/- 1 (mean +/- SEM) beats before termination in 26 episodes, stable atrial flutter evolved into atrial fibrillation in 3 episodes, and no cycle length change occurred before termination in 1 episode. In the open-chest studies, in all instances, spontaneous oscillations began 7 +/- 1 beats before termination. The only consistent oscillation pattern occurred for the last two beats: a long cycle length (149 +/- 9 milliseconds) followed by a much shorter cycle length (110 +/- 6 milliseconds) (P < .01). Activation maps demonstrated that all cycle length oscillations were explained by changes of conduction in an area(s) of slow conduction in the reentrant circuit. In two instances, the last (short) cycle length was associated with disappearance of an area of slow conduction. In all episodes, the last circulating reentrant wave front blocked in an area of slow conduction in the reentrant circuit. Although not tested, during the last beat, the very early arrival of the circulating reentrant wave front at an area of slow conduction suggests an important role for refractoriness, with head and tail interactions, resulting in block. CONCLUSIONS: Spontaneous termination of stable atrial flutter in the sterile pericarditis model (1) is preceded by beat-to-beat cycle length oscillations that result from changes in conduction in areas of slow conduction in the reentrant circuit and (2) results from block of the circulating reentrant wave front in an area of slow conduction.

Animals↗
PubMed1992

The use of temporal information in the regularization of the inverse problem of electrocardiography.

The inverse problem of electrocardiography is solved in order to reconstruct electrical events within the heart from information measured noninvasively on the body surface. These electrical events can be deduced from measured epicardial potentials; therefore, a noninvasive method of recovering epicardial potentials from body surface data is useful in clinical and experimental work. The ill-posed nature of this problem necessitates the use of regularization in the solution procedure. Inversion using Tikhonov zero-order regularization, a quasi-static method, had been employed previously and was able to reconstruct, with relatively good accuracy, important events in cardiac excitation (maxima, minima, etc.). Taking advantage of the fact that the process of cardiac excitation is continuous in time, one can incorporate information from the time progression of excitation in the regularization procedure using the Twomey technique. Methods of this type were tested on data obtained from a human-torso tank in which a beating canine heart was placed in the correct human anatomical position. The results show a marked improvement in the inverse solution when these temporal methods are used, and demonstrate that important physiological events (e.g., right ventricular breakthrough) not detected by the quasi-static approach, are reconstructed using these methods. In addition, the results indicate that as the time interval between sampled maps is reduced, the quality of the solutions that use this temporal regularization is greatly improved.

Action Potentials↗
PubMed1992

A model study of volume conductor effects on endocardial and intracavitary potentials.

An idealized mathematical model was developed to study the effects of variations in conductive and geometric parameters on measured endocardial and intracavitary potentials. The model consists of a spherical multielectrode probe located eccentrically within a system of concentric spheres that represent a blood cavity, myocardium, lung region, and surface muscle layer. Solutions were found for endocardial and intracavitary probe potentials produced by two different configurations of equivalent myocardial sources: 1) multiple activation wave fronts oriented radially, representing global fronts in the myocardium; and 2) pairs of equal and opposite dipoles on a line oriented tangentially to the endocardial surface, representing cardiac sources during early ectopic activation. It was found that the complexities of the cardiac source configurations are reflected in the endocardial potential but not in the associated probe potential, which exhibits a smoothed-out, low-amplitude distribution. In addition, probe potential depends on probe size and location within the cavity. Furthermore, endocardial and probe potentials are influenced by variations in the conductivity of different regions; an increase in blood conductivity results in a decrease in both endocardial and probe potential magnitudes produced by either type of cardiac sources, and an increase in myocardial conductivity results in an increase in both potential magnitudes, whereas an increase in lung conductivity results in an increase in the magnitude of the potential produced by radial sources but a small decrease in the magnitude of the potential produced by tangential sources. The effects of variations in skeletal muscle conductivity are negligible. The volume conductor effects of myocardial anisotropy (9:1 anisotropy ratio) are to attenuate both endocardial and probe potentials by as much as 60% and 71%, respectively, for radial sources and by 96% and 85%, respectively, for tangential sources. In conclusion, volume conductor influences should be considered in the interpretation of measured cavity potentials. Multiple myocardial events are resolved in endocardial potentials but not in potentials measured by an intracavitary multielectrode probe. This observation indicates that for the purpose of resolving cardiac activity, efforts should be directed at inverse reconstruction of endocardial potentials from potentials measured with an intracavitary probe.

Arrhythmias, Cardiac↗
PubMed1992

The electrocardiographic inverse problem.

Using the boundary element method in conjunction with Tikhonov zero-order regularization, we have computed epicardial potentials from body surface potential data in a realistic geometry heart-torso system. The inverse-reconstructed epicardial potentials were compared to the actual measured potentials throughout a normal cardiac cycle. Potential features (maxima, minima) were recovered with an accuracy better than 1 cm in their location. In this chapter, we use these data to illustrate and discuss computational issues related to the inverse-reconstruction procedure. These include the boundary element method, the choice of a regularization scheme to stabilize the inversion, and the effects of incorporating a priori information on the accuracy of the solution. In particular, emphasis is on the use of temporal information in the regularization procedure. The sensitivity of the solution to geometrical errors and to the spatial and temporal resolution of the data is discussed.

Animals↗
PubMed1991

Mathematical model of cellular basis for the respiratory sinus arrhythmia.

The respiratory sinus arrhythmia (RSA) is a vagally mediated oscillation in cardiac cycle length at the frequency of breathing. We developed a mathematical model that predicted the temporal and frequency dependence of the RSA. We used the mathematical model to examine the underlying cellular basis for the RSA at the level of the sinus node. We alternated efferent vagal activity between a low and a high frequency at the frequency of breathing. This oscillation caused the rate of acetylcholine (ACh) release to oscillate between a low and a high rate at the frequency of breathing. ACh degradation followed linear pharmacokinetics for physiological concentrations of ACh. Therefore, the concentration of ACh in neuroeffector junctions of the sinus node oscillated at the frequency of breathing. Membrane potential responded rapidly to changes in the concentration of ACh relative to the rate of ACh degradation. Thus, the time course of the RSA depended on the rate of ACh degradation. Membrane potential oscillated at several integer multiples of frequency of breathing and at various higher frequencies, which were integer multiples of the frequency of breathing and the frequencies of firing of the sinus node. However, computing cardiac cycle length from membrane potential eliminated the higher frequencies. Therefore, cardiac cycle length oscillated at several integer multiples of the frequency of breathing, but not at these higher frequencies.

Acetylcholine↗
PubMed1991

Onset of induced atrial flutter in the canine pericarditis model.

To test the hypothesis that induced atrial flutter evolves from a transitional rhythm, the onset of 99 episodes of induced atrial flutter (mean cycle length 135 +/- 18 ms) lasting greater than 5 min in 40 dogs with sterile pericarditis was first characterized. In 85 (86%) of the 99 episodes, atrial flutter was preceded by a brief period (mean 1.4 +/- 0.9 s, range 0.4 to 42) of atrial fibrillation. Then, in 11 open chest studies, atrial electrograms were recorded simultaneously from 95 pairs of right atrial electrodes during the onset of 18 episodes of induced atrial flutter (mean cycle length 136 +/- 16 ms). Atrial flutter was induced by a train of eight paced atrial beats, followed by one or two premature atrial beats (7 episodes) or rapid atrial pacing (11 episodes). A short period of atrial fibrillation (mean cycle length 110 +/- 7 ms) induced by atrial pacing activated the right atrium through wave fronts, which produced a localized area of slow conduction. Then unidirectional conduction block of the wave front occurred for one beat in all or a portion of the area of slow conduction. This permitted the unblocked wave front to turn around an area of functional block and return through the area of slow conduction that had developed the unidirectional conduction block, thereby initiating the reentrant circuit. The location of the unidirectional block relative to the direction of the circulating wave fronts determined whether the circus movement was clockwise or counterclockwise. The area of slow conduction and unidirectional conduction block occurred where the wave front crossed perpendicular to the orientation of the atrial muscle fibers, suggesting a role for anisotropic conduction. These areas included the high right atrial portion of the sulcus terminalis (10 episodes), the low right atrial portion of the sulcus terminalis (4 episodes) and the pectinate muscle region (4 episodes). It is concluded that the development of a localized area of slow conduction in the right atrium followed by unidirectional conduction block in this area produced during a short period of atrial fibrillation or rapid atrial pacing is necessary for atrial flutter to occur in this model.

Animals↗
PubMed1991

Termination of reentrant propagation by a single stimulus: a model study.

A computer model of a ring-shaped one-dimensional cardiac fiber was used to examine responses of reentrant propagation to premature stimuli applied under different degrees of head-tail interaction. Two different types (type I and type II) of termination window (TW) were identified. The type I TW was generated by functional inhomogeneity created by reentrant propagation. The width of the type I TW was proportional to the degree of cellular uncoupling. In contrast, uniform reduction in sodium channel conductance decreased the width of type I TW. The type II TW was generated by electrical alternans created by the head-tail interaction of the reentrant action potential. It was demonstrated that electrical alternans were most significant in medium degree head-tail interaction. For stronger or weaker head-tail interaction, the electrical alternans tended to decrease. The type II TW was located in excitable gaps following reentrant action potentials of short duration. Its size was proportional to the degree of electrical alternans. The type II TW was usually much larger than the type I TW. A premature conditioning stimulus induced alternans and created a type II TW. This response implies that a conditioning stimulus could facilitate greatly the termination of clinical reentrant arrhythmias by programmed electrical stimulation.

Action Potentials↗
PubMed1991

Electrocardiographic body surface potential mapping in the Wolff-Parkinson-White syndrome. Noninvasive determination of the ventricular insertion sites of accessory atrioventricular connections.

BACKGROUND: A reliable, noninvasive procedure to determine the location of accessory atrioventricular connections in patients with Wolff-Parkinson-White syndrome would add an important diagnostic tool to the clinical armamentarium. METHODS AND RESULTS: Body surface potential mapping (BSPM) using 180 electrodes in various-sized vests and displayed as a calibrated color map was used to determine the ventricular insertion site of the accessory atrioventricular (AV) connections in 34 patients with Wolff-Parkinson-White syndrome. Attempts were made to determine the 17 ventricular insertion sites described by Guiraudon et al. All 34 patients had an electrophysiologic study (EPS) at cardiac catheterization, and 18 had surgery so the ventricular insertion sites could be accurately located using EPS at surgery. A number of physiologic observations were also made with BSPM. CONCLUSIONS: The following conclusions were drawn: 1) BSPM using QRS analysis accurately predicts the ventricular insertion site of accessory AV connections in the presence of a delta wave in the electrocardiogram; 2) the ventricular insertion sites of accessory AV connections determined by BSPM and by EPS at surgery were identical or within one mapping site (1.5 cm or less) in all but four of 18 cases; three of the four exceptions had more than one accessory AV connection, and the other had a very broad ventricular insertion; 3) BSPM and EPS locations of the accessory AV connections correlated very well in the 34 cases despite the fact that BSPM determines the ventricular insertion site and EPS determines the atrial insertion site of the accessory AV connection; 4) as suggested by the three cases of multiple accessory AV connections, EPS and BSPM may be complementary since BSPM identified one pathway and EPS identified the other (in the case with a broad ventricular insertion, BSPM and EPS demonstrated different proportions of that insertion); 5) BSPM using ST-T analysis is very much less accurate in predicting the ventricular insertion site of accessory AV connections unless there is marked preexcitation; 6) standard electrocardiography using the Gallagher grid methodology (but with no attempt at stimulating maximal preexcitation) was not as accurate as QRS analysis of BSPM in predicting the ventricular insertion site of the accessory AV connection; however, exact comparison is hampered by the different number and size of the Gallagher and Guiraudon insertion sites; 7) BSPM using QRS analysis appears to be very accurate in predicting right ventricular versus left ventricular posteroseptal accessory AV connections; 8) typical epicardial right ventricular breakthrough, indicative of conduction via the specialized AV conduction system, occurs in all patients with left ventricular free wall accessory AV connections; 9) epicardial right ventricular breakthrough was not observed in cases with right ventricular free wall or anteroseptal accessory AV connections; 10) epicardial right ventricular breakthrough can occur in the presence of posteroseptal accessory AV connections, whether right or left ventricular; and 11) the delay in epicardial right ventricular breakthrough in cases with left ventricular insertion may provide a marker to estimate the degree of ventricular preexcitation.

Adult↗
PubMed1991

Multiplexing studies of effects of rapid atrial pacing on the area of slow conduction during atrial flutter in canine pericarditis model.

BACKGROUND: We report that rapid atrial pacing interrupts atrial flutter when the orthodromic wave front from the pacing impulse is blocked in an area of slow conduction in the reentry circuit. To characterize the area of slow conduction during atrial flutter and rapid pacing, we studied 11 episodes of induced atrial flutter, mean cycle length 157 +/- 20 msec, in eight dogs with sterile pericarditis. METHODS AND RESULTS: Atrial electrograms were recorded simultaneously from 95 pairs of right atrial electrodes during the interruption of atrial flutter by rapid atrial pacing, mean cycle length 139 +/- 21 msec. Areas of slow conduction during atrial flutter were demonstrated at one to three sites in the reentry circuit. After rapid pacing captured the reentry circuit, one area of slow conduction either disappeared (10 episodes) or the degree of slow conduction in an area of slow conduction decreased (one episode). Both changes were in association with activation of the region by a wave front from the pacing impulse that arrived from a direction different than that during the induced atrial flutter. Interruption of atrial flutter during rapid pacing occurred when the orthodromic wave front from the pacing impulse blocked in an area of slow conduction that had either newly evolved during rapid pacing (seven episodes) or that was previously present (four episodes). CONCLUSIONS: Areas of slow conduction present during atrial flutter and rapid pacing of atrial flutter are functional and depend on both the atrial rate and the direction of the circulating wave fronts. Interruption of atrial flutter by rapid pacing results from block of the orthodromic wave front of the pacing impulse in an area of slow conduction in the reentry circuit.

Animals↗
PubMed1991

A model of the ventricular cardiac action potential. Depolarization, repolarization, and their interaction.

A mathematical model of the membrane action potential of the mammalian ventricular cell is introduced. The model is based, whenever possible, on recent single-cell and single-channel data and incorporates the possibility of changing extracellular potassium concentration [K]o. The fast sodium current, INa, is characterized by fast upstroke velocity (Vmax = 400 V/sec) and slow recovery from inactivation. The time-independent potassium current, IK1, includes a negative-slope phase and displays significant crossover phenomenon as [K]o is varied. The time-dependent potassium current, IK, shows only a minimal degree of crossover. A novel potassium current that activates at plateau potentials is included in the model. The simulated action potential duplicates the experimentally observed effects of changes in [K]o on action potential duration and rest potential. Physiological simulations focus on the interaction between depolarization and repolarization (i.e., premature stimulation). Results demonstrate the importance of the slow recovery of INa in determining the response of the cell. Simulated responses to periodic stimulation include monotonic Wenckebach patterns and alternans at normal [K]o, whereas at low [K]o nonmonotonic Wenckebach periodicities, aperiodic patterns, and enhanced supernormal excitability that results in unstable responses ("chaotic activity") are observed. The results are consistent with recent experimental observations, and the model simulations relate these phenomena to the underlying ionic channel kinetics.

Action Potentials↗
PubMed1990

Multicategory classification of body surface potential maps.

A statistical classification method is suggested for body surface potential maps (BSPM). The initial data reduction utilizes the Fourier expansion and time integration, resulting in physiological-oriented features. Based on Fischer's criterion, optimal discriminant vectors are used to map the features to an optimal subdomain. Experimental criteria determine the dimensionality of the subdomain and the number of features to be mapped into it. Classification is performed in two steps. In the first, a k-nearest neighbor (k-NN) rule is used for every two-category problem, the results of which are fed into a voting rule for final classification. The method is tested with 123 patients divided into four categories: normal (NR), ischemia (IS), myocardial infarction (MI), and left bundle branch block (LB) patients. The success is between 88% (for IS) and 100% (for LB) for QRS segment integration. Departure maps were used to explain the misclassified patterns.

Algorithms↗