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Biomedical subjects

R L Lux

Publications and source records attributed to R L Lux.

At least 73 records · Page 4Linked to original sources

Epicardial potential mapping. Effects of conducting media on isopotential and isochrone distributions.

BACKGROUND: Epicardial excitation sequences, recovery sequences, and potential distributions are recorded from patients during surgery and from animals in the research laboratory for a variety of purposes. During such recordings, a portion of the cardiac surface is exposed to air, and the remainder of the epicardial surface variably is in contact with conductive tissue. No systematic studies document the degree to which these different conditions affect measured excitation times, potential distributions, and/or the configuration of epicardial electrograms. METHODS AND RESULTS: Epicardial potential distribution was recorded from five isolated, perfused hearts using a 64-unipolar-lead sock. Data were recorded first with the heart suspended in air and then with the heart immersed in a heated tank filled sequentially to full and half-full levels with conductive Tyrode's solution and then NaCl-sucrose solution. These solutions had resistivity less than and more than that of blood, respectively, and air was assumed to have infinite resistivity. Epicardial potentials were recorded from two hearts before removal from the chest, both with and without a latex sheet insulating the heart from the pericardial cradle. Amplitude of recorded potentials from both intact and isolated hearts was markedly higher when the heart was surrounded by an insulating medium, but locations of positive and negative regions were less affected by surrounding medium. Isochrone activation maps calculated using the minimum derivative of the QRS (intrinsic deflection) were not affected by the conductivity of media surrounding the heart. CONCLUSIONS: The present study provides evidence that isochrone maps recorded at surgery are not distorted by exposure of the cardiac surface to insulating air. Results suggest that epicardial isochrones recorded during cardiac surgery could be used in patients to assess the accuracy of "inverse" procedures that noninvasively compute epicardial electrograms and isochrones from body surface potentials.

Animals↗

Determination of local myocardial electrical activation for activation sequence mapping. A statistical approach.

Electrical activation sequence mapping requires accurate identification of local activation, but because extracellular recordings do not exclusively reflect local events, complex electrograms may be difficult to interpret. In such cases, the assignment of local activation is subject to error that could affect interpretation of the resulting activation maps. The purpose of this investigation was to develop an approach that would provide quantitative indexes of error in the determination of local activation. An electrode array with 64 closely spaced unipolar electrodes was used to record from the left ventricular surface during open heart surgery. Electrograms with multiple deflections were recorded from four patients with scarred myocardium; two other patients with normal myocardial function served as controls. Each of 784 deflections was scored on the basis of three features: evidence for propagation, the configuration of the bipolar signal, and the effect of changing from the chest to an average reference. Local activation was considered probable if evidence for all three features was present and improbable if none of the three features was present. Deflections that were ambiguous with respect to this standard were excluded. Of over 30 test variables analyzed, the three with the greatest power to discriminate signals due to local activation from those due to distant activity were 1) a linear combination of the extracellular potential plus the ratio of the second derivative and the extracellular potential, 2) the second derivative, and 3) the minimum (greatest negative) first derivative. For each of these variables, the threshold value providing the greatest performance was identified by the maximum quality of efficiency, an index of agreement. This statistical approach provides an objective basis for determining local activation and provides a quantitative assessment of error that could enhance interpretation of electrical activation sequence maps.

Differential Threshold↗

Correlation between in vivo transmembrane action potential durations and activation-recovery intervals from electrograms. Effects of interventions that alter repolarization time.

Classic cable theory was used to analyze the relation between the activation-recovery interval measured from unipolar electrograms and transmembrane action potential duration. Theoretic analysis demonstrated that the temporal derivative of the extracellular potential is proportional to a spatial weighting of the third temporal derivative of the transmembrane action potentials along a cable with uniform propagation in a homogeneous medium. Thus, the activation-recovery interval, measured as the interval between times of minimum derivative (Vmin) of the QRS and maximum derivative (Vmax) of the T wave, should be related to action potential duration, measured as the interval between times of Vmax of the upstroke and Vmin of the downstroke of the transmembrane action potential. This relation was examined experimentally in 12 anesthetized dogs. Unipolar electrograms and transmembrane action potentials were recorded simultaneously from sites within 2 mm of each other during control states, cardiac sympathetic nerve stimulation, localized epicardial warming, and graded reductions in myocardial perfusion. The heart was paced from several sites. There was close correlation between activation-recovery interval and action potential duration measurements taken during cardiac sympathetic nerve stimulation and local epicardial warming (r = 0.96 and 0.99 for cardiac sympathetic nerve stimulation and warming, respectively). In five animals in which coronary perfusion pressure was gradually lowered, the variables correlated closely over a range of values from 62 to 212 msec (r = 0.98). However, although the overall correlation was good and mean differences between activation-recovery interval and action potential duration were small, in individual cases there were differences up to 24 msec.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗

Conduction velocity depression and drug-induced ventricular tachyarrhythmias. Effects of lidocaine in the intact canine heart.

Depression of myocardial conduction velocity can be an important mechanism of action of antiarrhythmic drugs but it can also facilitate arrhythmogenesis. We used lidocaine in an anesthetized canine preparation to address the hypothesis that drug-induced rate-dependent conduction velocity depression causes ventricular tachyarrhythmias. A closely spaced square array of 64 electrodes was used to determine conduction velocity longitudinal and transverse to epicardial ventricular fiber direction. Lidocaine caused rate-dependent decreases in conduction velocity that were proportionately greater in the longitudinal direction at the shortest pacing cycle lengths. Conduction velocity depression developed rapidly in the presence of lidocaine with a new steady state present by the second beat of the rapid train. Recovery from rate-dependent depression of conduction velocity was exponential with a time constant of 122 +/- 20 msec (mean +/- SD) in the longitudinal direction and 114 +/- 30 msec in the transverse direction; this difference was not significant. The relation between conduction velocity depression and ventricular arrhythmias was assessed by pacing for 3 minutes at cycle lengths of 1,000, 500, 300, and 250 msec, and for 1 minute at a cycle length of 200 msec. Arrhythmias did not occur in the baseline period in the dogs that received lidocaine, nor in 12 control dogs that were subjected to the same stimulation protocol except that saline was administered in place of lidocaine. Sustained polymorphic ventricular tachycardia (VT) occurred in six of 16 dogs given lidocaine. VT occurred in the presence of relatively high plasma lidocaine concentrations (8.4 +/- 2.3 micrograms/ml) and only at pacing cycle lengths of 300 msec or shorter. The dogs that developed VT demonstrated greater rate-dependent depression of conduction velocity than the other dogs, and activation patterns obtained just before the onset of VT showed marked conduction disturbances. Furthermore, QRS prolongation, loss of one-to-one capture, and increasingly distorted activation patterns preceded the onset of VT during fixed-rate pacing, suggesting progressive sodium channel block. In summary, rate-dependent conduction velocity depression and nonuniform activation were associated with VT in this model and can be responsible for some arrhythmias induced by antiarrhythmic drugs.

Animals↗

Determination of transmural location of onset of activation from cardiac surface electrograms.

Methods of estimating depth of origin of ventricular activation from cardiac surface electrograms were evaluated in experiments on eight dogs. The ventricles were paced via multielectrode needle arrays placed transmurally in from four to six locations in the wall of the left ventricle. A multiplexed data-recording system was used to simultaneously record from 64 unipolar cardiac surface electrodes during pacing at each multielectrode needle site. The four indexes evaluated were the maximum and average gradients of activation isochrones around the site of earliest epicardial activation, the QRS area at the site of earliest epicardial activation, the interval between the QRS onset computed from all 64 epicardial surface electrograms, and the time of the minimum dV/dt in the electrogram displaying the earliest epicardial activation time (t(ee)-t(rmso) interval). Correlation coefficients between depth of stimulation and average and maximum gradients of isochrones, QRS area at the site of earliest epicardial activation, and t(ee)-t(rmso) interval were 0.985 or higher. These methods, particularly those involving gradients of isochrones, should be useful for evaluating electromaps of patients undergoing surgery for ablation of tachyarrhythmias.

Analysis of Variance↗

Effect of nontransmural necrosis on epicardial potential fields. Correlation with fiber direction.

The effect of nontransmural necrosis on epicardial potential distributions was studied in 13 dogs. In previous studies, left ventricular epicardial pacing generated epicardial potential maps at QRS onset with a negative central area and two positive areas that faced the portions of the wavefront propagating along fibers. Subsequently, the positive areas expanded in a counterclockwise direction by 90 degrees to 120 degrees. In those studies, the rotatory expansion of the positive areas was tentatively attributed to the spread of excitation through deep myocardial layers, where fiber direction rotated counterclockwise from epicardium to endocardium. To test this hypothesis, we tried to interrupt the counterclockwise expansion of the positive area by creating localized, nontransmural necrosis at various depths in the left ventricular wall by injection of formalin or application of laser energy. Epicardial potential maps were obtained from a grid of 12 x 15 electrodes on a 44 x 56-mm area. Epicardial pacing from selected sites generated epicardial maps in which some positive areas were missing compared with controls. The direction of the straight line joining the pacing site to the site of missing positivity correlated well with the average fiber direction in the necrotic mass (r = 0.82, p less than 0.01). Angle between epicardial fiber direction and the straight line described above correlated well with the average depth of the necrosis, expressed as percent of the wall thickness (r = 0.95, p less than 0.01). These data support the hypothesis that the counterclockwise expansion of the epicardial positivity occurring after epicardial pacing results from excitation spreading along deep fibers.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Changes in the ECG and myocardial blood flow of the right and left ventricular walls under acute pulmonary arterial stenosis].

For studying the effect of regional myocardial blood flow changes on the epicardial ECG of right and left ventricular walls under acute right ventricular pressure overload, we mapped the epicardial using 64-channel shock electrodes, and estimated the myocardial blood flow with radioactive microspheres. In 9 anesthetized open-chest dogs, the main pulmonary artery was gradedly constricted to the level of mild (peak RV pressure: PRVP, 50-70 mmHg), moderate (PRVP, 70-80 mmHg) and severe stenosis (PRVP, over 80 mmHg). Labeled microspheres were injected into the left atrium before and after the PA constriction, and the epicardial ECGs were recorded continuously. After the completion of the experiment, 9 areas of each right and left ventricular wall were excised. The myocardium was divided into three layers and the flow data were compared to the changes of ECG parameters. In the cases where there was severe PA stenosis, the right ventricular myocardial blood flow decreased to a significantly greater degree (63% reduction from the control), especially in the subepicardial layer, than the flow in the left ventricle (37% reduction from the control). ST potential, STT and QRST Area Map increased in the right ventricle but decreased in the left ventricle. Activation Recovery Time of the right ventricle decreased due to the severe ischemia of the right ventricle. The value of QRS Area Map of the left ventricle decreased significantly in parallel with the decrease in cardiac output.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

Rate-related electrophysiologic effects of long-term administration of amiodarone on canine ventricular myocardium in vivo.

The electrophysiologic effects of amiodarone were examined in 13 dogs that received 30 g amiodarone orally during 3 weeks and compared with 13 control dogs that did not receive amiodarone. Longitudinal and transverse epicardial conduction velocities were estimated with a square array of 64 closely spaced electrodes and a computer-assisted acquisition and analysis system. Amiodarone caused a rate-dependent decrease in conduction velocity with a slightly greater effect in the longitudinal direction of propagation. Rate-related depression of conduction velocity developed rapidly after abrupt shortening of the pacing cycle length; 67% of the change occurred between the first two beats of the rapid train, and little change occurred after the 10th beat. Recovery from use-dependent depression of conduction velocity was exponential with a mean time constant of 447 +/- 172 msec in the longitudinal direction and 452 +/- 265 msec in the transverse direction. Repolarization intervals, defined as the interval between the activation time and the repolarization time in the unipolar electrograms, correlated highly with refractory period determinations in the absence and presence of amiodarone at each cycle length tested. The increase in repolarization intervals and refractory periods resulting from amiodarone treatment did not vary with cycle length. Amiodarone treatment also resulted in a significant rate-related reduction in systolic blood pressure. The systolic blood pressure in the group that received amiodarone decreased by a mean of 50 +/- 23% between steady-state pacing cycle lengths of 1,000 and 200 msec, whereas the corresponding decrease in the control group was 21 +/- 32% (p less than 0.05). Plasma and myocardial amiodarone and desethylamiodarone levels were comparable to those observed clinically. We conclude that long-term amiodarone administration causes rate-dependent reductions in conduction velocity and blood pressure and causes rate-independent increases in repolarization intervals.

Amiodarone↗

Sources of variability in normal body surface potential maps.

Within-group variability of body surface potential maps was assessed on data from 685 carefully validated normal subjects (348 men and 337 women). Sources of within-group variability were evaluated by subgrouping maps by patient sex, age, height, and weight. Contribution of reproducibility error to total variance was assessed in a separate group of 52 normal subjects in whom multiple maps were recorded. Total variance was significantly lower in women than in men. Total variance tended to decrease with age, and the greatest decrease occurred in men during the 3rd decade. The ratio of total variance to mean signal energy showed a slow decrease with age for each group. Results suggest that the dominant source of within-group variability arises from variability of cardiac electric sources while the influence of volume conductor variability is significantly less. Variability due to measurement reproducibility was approximately half of the total variance.

Adult↗

Activation sequence at the onset of arrhythmias induced by localized myocardial warming and programmed premature stimulation in dogs.

The effect of localized shortening of ventricular repolarization on arrhythmia vulnerability was studied in 10 pentobarbital anesthetized dogs. An area of the anterior right ventricle was warmed by directing a light beam through a condenser lens assembly and a rectangular aperture. Arrhythmia vulnerability was assessed with low-amplitude programmed stimulation. Activation sequence maps were constructed from electrograms recorded simultaneously from 40 epicardial sites and 24 endocardial sites in and surrounding the warmed area. Recordings were taken during regular atrial and ventricular drives and during programmed stimulation in control periods and during myocardial warming. Spontaneous activity could not be induced with low-amplitude programmed stimulation during control periods in any dog. During myocardial warming arrhythmias were induced in every dog. Most induced arrhythmias had features consistent with local reentry. However, activation sequence at the onset of some arrhythmias strongly resembled that of superventricular activation and was consistent with reentry involving the His-Purkinje system. The findings provide evidence that a localized area with short ventricular repolarization is an abnormality sufficient to increase arrhythmia vulnerability and also that even in this relatively simple setting there can be multiple mechanisms for arrhythmias.

Animals↗

Relation of cardiac surface QRST distributions to ventricular fibrillation threshold in dogs.

The relation between ventricular fibrillation threshold (VFT) and cardiac surface QRST area distributions was studied in eight pentobarbital-anesthetized dogs. Unipolar epicardial electrograms were recorded from 64 sites evenly distributed on the right and left ventricles. Localized areas of short repolarization properties were produced by directing five intensities of light onto the surface of the anterior right ventricle through apertures of three sizes. VFT, measured at the center of the lesion, decreased during warming and had a high negative correlation to the change (warming-control) in QRST area (delta QRST1) in the electrogram recorded from the center of the lesion. This correlation was independent of lesion size. For the six experiments, the correlation coefficients for 400-, 800-, and 1,600-mm2 lesions averaged -0.95, -0.94, and -0.96, respectively. The correlation between VFT and delta QRST1 without regard to lesion size averaged -0.88. VFT also had a negative correlation to root mean square (RMS)delta QRST because of warming. RMS delta QRST was calculated from the change in QRST areas (warming-control) in all 64 electrograms. The correlation between VFT and RMS delta QRST was dependent on lesion size. For all experiments, the correlation between VFT and RMS delta QRST averaged -0.97, -0.93, and -0.93 for 400-, 800-, and 1,600-mm2 lesions, respectively. The correlation between VFT and RMS delta QRST without regard to lesion size, however, was considerably lower, -0.59. The results of this study provide the first direct evidence that VFT is correlated with cardiac surface QRST area distributions.

Animals↗

Fine detail in body surface potential maps: accuracy of maps using a limited lead array and spatial and temporal data representation.

In order to evaluate the accuracy with which a limited lead array can be used to estimate fine details of the thoracic distribution of cardiac potentials, we compared 192-lead body surface maps and those constructed using a subset of 32 leads. We also evaluated preservation of detail in body surface maps reconstructed following spatial and temporal data representation, a method proposed for quantitative comparison of maps. Maps were analyzed with respect to four previously reported normal map features recorded with extensive lead arrays. The maps constructed from 32 leads accurately reproduced all map features with 92% or greater accuracy. Maps constructed after spatial and temporal data representation had a reproduction accuracy of 93% and 98% respectively for two map features more than 100 microV in amplitude but accuracy with respect to the two map features less than 100 microV in amplitude was 86% and 59% respectively. The study demonstrates that a selected limited lead array permits accurate estimation of the body surface distribution of cardiac potentials even when potentials are low level or occur in regions not directly sampled by a recording electrode. To represent potentials of less than 100 microV, more coefficients would be required to permit accurate spatial and temporal representation.

Electrocardiography↗

Detection and localization of coronary artery disease with body surface mapping in patients with normal electrocardiograms.

Patients with clinically significant coronary artery disease often have normal resting electrocardiograms. Clinical and experimental studies have shown that body surface potential maps provide improved recognition of some disease states and more regionally selective information than standard electrocardiograms. Body surface maps were recorded at rest from 41 symptomatic patients with angiographically documented coronary artery disease and normal electrocardiograms. Patient maps were statistically compared with maps recorded from 644 normal subjects with the use of previously reported data representation technique. By this technique, maps from patients with symptomatic coronary artery disease and normal electrocardiograms were separated from maps of normal subjects with a sensitivity and specificity greater than 94%. The majority of discriminating information was present in the QRS interval. Fifteen of the 41 symptomatic patients had documented single-vessel coronary disease and their maps were separately compared with normal maps. Average maps from each of three patient groups with single-vessel disease contained abnormal patterns during the QRS interval that were unique to the vessel affected. In comparison with a average map from normal subjects, the average map from the group with left anterior descending coronary disease showed lower potentials over the anterior and inferolateral thorax during the early to mid QRS interval, the average map from the circumflex disease group showed decreased potentials around the entire inferior thorax in the mid to late QRS interval, and the average map from the right coronary disease group showed decreased potentials over the right anterior thorax during the mid to late QRS interval.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Effects of age, sex, and body habitus on QRS and ST-T potential maps of 1100 normal subjects.

Body surface potential maps provide more detailed regional cardiac electrophysiologic information than the standard electrocardiogram. We performed a large-scale study of a normal population to form a comparison base for evaluation of the clinical utility of this technique. We analyzed body surface maps from 1113 normal subjects from 10 to 80 years old to detail map features as a function of age, sex, and body habitus. Maps were analyzed by visual inspection and by a spatial and temporal data reduction technique that allows statistical comparison of map features. On average, both QRS and ST-T potentials decreased with increasing age. Potential pattern distributions remained constant from 10 to 40 years. Beyond age 40, larger numbers of maps from normal subjects showed depolarization patterns consistent with delayed activation of the left anterior fasicle, despite normal 12-lead electrocardiograms. Only minor QRS potential amplitude and distribution differences were noted when male and female subjects were compared within groups of similar age and body habitus. Male subjects consistently showed greater average T potential amplitudes. Slender body habitus was associated with a more horizontal "zero" potential line. In female subjects over age 40 there were more extensive low-level negative potentials recorded over the precordium during the ST segment than in men. This study defines the range of normal body surface potential maps in a large clinically normal population and provides a basis for qualitative and statistical comparison with map features of patients with disease.

Adolescent↗

Correlation between refractory periods and activation-recovery intervals from electrograms: effects of rate and adrenergic interventions.

Unipolar electrograms from ventricular epicardium in dogs were analyzed for the timing of local excitation and repolarization with computer assistance. The most rapid decrease in voltage in the QRS (dV/dt min) was used to determine local excitation time, and the maximum rate of voltage increase (dV/dt max) near the peak of the T wave was used to time local repolarization. The difference between dV/dt min and dV/dt max, the activation-recovery interval, is theoretically related to the net effect of the durations of the action potentials at that site. Paired data for refractory periods and activation-recovery intervals obtained from the same electrodes during fixed activation orders were obtained before and during repolarization changes induced by changes in cycle length, infusion of norepinephrine, and cardiac sympathetic nerve stimulation. Correlation coefficients were close to 1.00 and standard errors were 2.0 to 4.3 msec for changes at individual sites. Pooling of data from multiple sites increased standard errors and reduced correlation coefficients. Results provide quantification of errors in the use of unipolar electrograms to time local repolarization changes induced by variations in rate and adrenergic tone. They should increase the practical usefulness of the unipolar electrogram as a tool for assessing the time course and spatial distribution of repolarization changes.

Animals↗

Effect of caval occlusion on the magnitude of unipolar atrial electrograms in dogs.

Studies were done on eight mongrel dogs anesthetized with pentobarbital sodium to assess the effects of acute changes in heart volume on the magnitude of electrocardiographic potentials recorded from the right atrium. Following midsternotomy, acute changes in heart volume were produced by occlusion of the superior vena cava (SVC), inferior vena cava (IVC), or both vena cavae while heart rate was controlled by pacing the right atrium. P-wave area, defined by integrating absolute value of the P wave over time, increased by 8.2 +/- 7.4% during SVC occlusion, 13.3 +/- 8.5% during IVC occlusion, and 23.6 +/- 16.2% during occlusion of both vena cavae. Areas of ventricular complexes appearing in atrial electrograms decreased by 6.6 +/- 6.2% during SVC occlusion, 11.1 +/- 6.7% during IVC occlusion, and 15.2 +/- 9.2% during occlusion of both vena cavae. These results are compatible with predominately tangential activation of the atrium and radial excitation of the ventricle and provide experimental confirmation of the "Brody effect."

Animals↗