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Biomedical subjects

R H Clayton

Publications and source records attributed to R H Clayton.

At least 19 recordsLinked to original sources
PubMed2006

Initiation of re-entry in an excitable medium: structural investigation of cardiac tissue using a genetic algorithm.

The detailed mechanisms by which re-entry and ventricular fibrillation are initiated in the heart remain poorly understood because they are difficult to investigate experimentally. We have used a simplified excitable media computational model of action potential propagation to systematically study how re-entry can be produced by diffuse regions of inexcitable tissue. Patterns of excitable and inexcitable tissue were generated using a genetic algorithm. The inexcitable tissue was modeled in two ways: (i) diffusive, electrically connected but inexcitable tissue, or (ii) zero-flux, areas of tissue electrically disconnected in the same way as zero-flux boundary conditions. We were able to evolve patterns of diffuse inexcitable tissue that favored re-entry, but no single structure or pattern emerged. Diffusive inexcitable regions were inherently less arrhythmogenic than zero-flux inexcitable ones.

Algorithms↗
PubMed2005

Phase singularities and filaments: simplifying complexity in computational models of ventricular fibrillation.

In the whole heart, millions of cardiac cells are involved in ventricular fibrillation (VF). Experimental studies indicate that VF is sustained by re-entrant activity, and that each re-entrant wave rotates around a filament of phase singularity. Filaments act as organising centres, and offer a way to simplify and quantify the complex spatio-temporal behaviour observed in VF. Where a filament touches the surface of fibrillating myocardium re-entrant activity can be observed, however the behaviour of filaments within bulk ventricular myocardium is difficult to observe directly using present experimental techniques. Large scale computational simulations of VF in three-dimensional (3D) tissue offer a tool to investigate the properties and behaviour of filaments, and the aim of this paper is to review recent advances in this area as well as to compare recent computational studies of fibrillation in whole ventricle geometries.

Animals↗
PubMed2005

Dynamical and cellular electrophysiological mechanisms of ECG changes during ischaemia.

The interpretation of normal and pathological electrocardiographic (ECG) patterns in terms of the underlying cellular and tissue electrophysiology is rudimentary, as the existing theories rely on geometrical aspects. We relate effects of sub-endocardial ischaemia on the ST-segment depression in ECG to patterns of transmural action potential propagation in a one-dimensional virtual ventricular wall. Our computational study exposes two electrophysiological mechanisms of ST depression: dynamic-predominantly positive spatial gradients in the membrane potential during abnormal repolarization of the wall, produced by action potential duration changes in the ischaemic region; and static-a negative spatial gradient of the resting membrane potential between the normal and ischaemic regions. Hyperkalaemia is the major contributor to both these mechanisms at the cellular level. These results complement simulations of the effects of cardiac geometry on the ECG, and dissect spatio-temporal and cellular electrophysiological mechanisms of ST depression seen in sub-endocardial ischaemia.

Action Potentials↗
PubMed2001

Re-entrant cardiac arrhythmias in computational models of long QT myocardium.

The long QT syndrome (LQTS) is an inherited disorder in which repolarization of cardiac ventricular cells is prolonged. Patients with the LQTS are at an increased risk of ventricular cardiac arrhythmias. Two phenotypes of the inherited LQTS are caused by defects in K(+)channels (LQT1 and LQT2) and one by defects in Na(+)channels (LQT3). Patients with LQT1 are more likely to have self-terminating arrhythmias than those with LQT3. The aim of this computational study was to propose an explanation for this finding by comparing the vulnerability of normal and LQT tissue to re-entry, and estimating the likelihood of self-termination by motion of re-entrant waves to an inexcitable boundary in simulated LQT1, LQT2 and LQT3 tissue. We modified a model of mammalian cardiac cells to simulate LQT1 by reducing maximal I(K(s))conductance, LQT2 by reducing maximal I(K(r))conductance, and LQT3 by preventing complete inactivation of I(Na)channels. Each simulated phenotype was incorporated into a computational model of action potential propagation in one- and two-dimensional homogeneous tissue. Simulated LQT tissue was no more vulnerable to re-entry than simulated normal tissue, but the motion of re-entrant waves in simulated LQT1 tissue was between 2 and 5 times greater than the motion of re-entrant waves in simulated LQT2 and LQT3 tissue. These findings suggest that LQT arrhythmias do not result from increased vulnerability to re-entry, and that re-entry once initiated is more likely to self-terminate by moving to an inexcitable tissue boundary in LQT1 than in LQT2 and LQT3. This finding is consistent with clinical observations.

Action Potentials↗
PubMed2001

Computational models of normal and abnormal action potential propagation in cardiac tissue: linking experimental and clinical cardiology.

Computational models have the potential to make a huge impact on our understanding of normal and abnormal cardiac function. The aim of this article is to review tools that have been developed to simulate the electrophysiology of cardiac cells and tissue, and to show how computational models have been used to gain insight into normal and abnormal action potential propagation. Some of the practical problems experienced in the development and application of these models are described, and examples are given.

Action Potentials↗
PubMed1999

Linear and non-linear analysis of the surface electrocardiogram during human ventricular fibrillation shows evidence of order in the underlying mechanism.

Ventricular fibrillation (VF) is a poorly understood yet potentially lethal cardiac arrhythmia. The electrocardiogram (ECG) time series of VF is investigated by comparison of the linear and non-linear features of VF time series and surrogates in which internal correlations have been destroyed. From 40 ECG time series of human VF and 40 surrogate time series, three quantities are evaluated: the percentage of the linear time-frequency distribution (TFD) exceeding a threshold, the non-linear coarse-grained correlation dimension (Dcg), and the percentage of diagonal lines in the non-linear recurrence plot longer than 10 elements (D10). It is found that the mean (SD) percent threshold TFD and Dcg are higher for the surrogates (6.7% (1.3) and 5.3 (0.6)) than the VF time series (5.6% (0.7) and 3.8 (0.9)), whereas the mean D10 is higher for the VF time series (49% (13)) than the surrogates (32% (7)). All of these differences are significant (p < 0.0001) and indicate greater order in the VF time series than in the surrogates. It is therefore shown that both linear and non-linear signal analysis demonstrate order in the ECG time series of VF.

Electrocardiography↗
PubMed1999

Coherence between body surface ECG leads and intracardiac signals increases during the first 10 s of ventricular fibrillation in the human heart.

Ventricular fibrillation (VF) in the human heart is not well understood. The aim of this study was to measure changes in the phase relationship between the body surface ECG and intracardiac electrograms recorded during the first 10 s of human VF. We studied 11 episodes of VF and measured the coherence of (a) ECG lead I and ECG lead V1, (b) ECG lead V1 and the right ventricular apex (RVA) electrogram, and (c) ECG lead V1 and the smoothed RVA electrogram. Each coherence measurement was the average of the magnitude squared coherence function in the range 0-60 Hz, and measurements were made 1, 3, 5, 7 and 9 s after the onset of VF. Overall, the mean (SD) coherence was 31(6)% between ECG leads I and V1, 17(3)% between ECG lead V1 and the RVA electrogram, and 20(4)% between ECG lead V1 and the smoothed RVA electrogram. All three measurements of coherence increased significantly between 1 and 9 s with mean (SD) rates of 0.97(1.01)% s(-1), 0.8(1.18)% s(-1) and 0.82(1.19)% s(-1) respectively. These results show that propagation in human VF becomes more organized during the first 10 s of VF. This may be an optimal window for defibrillation.

Cardiac Catheterization↗
PubMed1998

Reproducibility of three different methods of measuring baroreflex sensitivity in normal subjects.

1. Baroreflex sensitivity is a useful tool for investigating cardiovascular reflexes in a number of clinical settings. Several different methods of measuring baroreflex sensitivity are available. In order to determine a clinically useful non-invasive method of measuring baroreflex sensitivity we compared two methods (spectral analysis and the Valsalva manoeuvre) with regard to reproducibility, agreement with a standard invasive method (phenylephrine infusion) and failure rate.2.Twenty-six healthy subjects aged 22 to 63 years attended on three separate occasions for measurement of baroreflex sensitivity using the different methods. The effect of a recent head-up tilt on baroreflex sensitivity was measured.3. Reproducibility was best for the low-frequency component of the spectral method [coefficient of variation 25.0% (range 3.5-42.4%)] and worst for the Valsalva method [coefficient of variation 29.3% (range 13.8-93.1%)]. Both non-invasive methods overestimated values compared with the phenylephrine method [bias of low-frequency component of the spectral method, 1.17 (0.38-3.6); bias of the Valsalva method, 1.13 (0.19-6.7)]. The high-frequency component of the spectral method did not agree with the phenylephrine method.4. The spectral analysis method had the fewest failures (seven subjects with a failure on at least one occasion), and the phenylephrine method the most (16 subjects with a failure on at least one occasion). A short head-up tilt did not affect the subsequent non-invasive measurement of baroreflex sensitivity.5. It was concluded that the low-frequency component of the spectral method was the most clinically useful non-invasive measurement of baroreflex sensitivity.

Adult↗
PubMed1997

Effects of aerobic exercise training and yoga on the baroreflex in healthy elderly persons.

It is unclear whether the age-associated reduction in baroreflex sensitivity is modifiable by exercise training. The effects of aerobic exercise training and yoga, a non-aerobic control intervention, on the baroreflex of elderly persons was determined. Baroreflex sensitivity was quantified by the alpha-index, at high frequency (HF; 0.15-0.35 Hz, reflecting parasympathetic activity) and mid-frequency (MF; 0.05-0.15 Hz, reflecting sympathetic activity as well), derived from spectral and cross-spectral analysis of spontaneous fluctuations in heart rate and blood pressure. Twenty-six (10 women) sedentary, healthy, normotensive elderly (mean 68 years, range 62-81 years) subjects were studied. Fourteen (4 women) of the sedentary elderly subjects completed 6 weeks of aerobic training, while the other 12 (6 women) subjects completed 6 weeks of yoga. Heart rate decreased following yoga (69 +/- 8 vs. 61 +/- 7 min-1, P < 0.05) but not aerobic training (66 +/- 8 vs. 63 +/- 9 min-1, P = 0.29). VO2 max increased by 11% following yoga (P < 0.01) and by 24% following aerobic training (P < 0.01). No significant change in alpha MF (6.5 +/- 3.5 vs. 6.2 +/- 3.0 ms mmHg-1, P = 0.69) or alpha HF (8.5 +/- 4.7 vs. 8.9 +/- 3.5 ms mmHg-1, P = 0.65) occurred after aerobic training. Following yoga, alpha HF (8.0 +/- 3.6 vs. 11.5 +/- 5.2 ms mmHg-1, P < 0.01) but not alpha MF (6.5 +/- 3.0 vs. 7.6 +/- 2.8 ms mmHg-1, P = 0.29) increased. Short-duration aerobic training does not modify the alpha-index at alpha MF or alpha HF in healthy normotensive elderly subjects. alpha HF but not alpha MF increased following yoga, suggesting that these parameters are measuring distinct aspects of the baroreflex that are separately modifiable.

Aged↗
PubMed1997

Baroreflex function in sedentary and endurance-trained elderly people.

OBJECTIVE: to determine the differences associated with age and endurance exercise training on the baroreflex function of healthy subjects. DESIGN: cross-sectional study. SETTING: university research department. PARTICIPANTS: 26 (10 female) sedentary, healthy, normotensive elderly subjects (mean age 67 years, range 62-81), eight (two female) elderly endurance-trained athletes (66 years, 62-69) and eight (two female) young (30 years, 25-34) subjects. MEASUREMENTS: baroreflex sensitivity was quantified by the alpha-index, at high frequency (HF, 0.15-0.35 Hz) and mid frequency (MF, 0.05-0.15 Hz), derived from spectral and cross-spectral analysis of spontaneous fluctuations in heart rate and blood pressure. RESULTS: resting heart rate was significantly lower in endurance-trained athletes than sedentary elderly people (58 +/- 12 versus 68 +/- 11 min(-1), P < 0.05) but not different to that in healthy young subjects (63 +/- 9 min[-1]). alpha(HF) in sedentary elderly subjects (8.1 +/- 4.2 ms.mm Hg[-1]) was lower than both endurance-trained elderly athletes (14.8 +/- 4.8 ms.mm Hg(-1), P < 0.05) and healthy young subjects (28.3 +/- 21.8 ms.mm Hg(-1), P < 0.05) and was not significantly different between endurance-trained elderly athletes and healthy young subjects (P = 0.10). alpha(MF) in healthy young subjects (15.4 +/- 8.8 ms.mm Hg[-1]) was greater than in sedentary elderly subjects (6.5 +/- 3.2 ms.mm Hg(-1), P < 0.01) and endurance-trained elderly athletes (6.9 +/- 2.0 ms.mmHg(-1), P < 0.01), while there was no significant difference between the two elderly groups (P = 0.66). CONCLUSIONS: both components of the baroreflex measured by the alpha-index show a decrease with age. Elderly endurance-trained athletes have less reduction in the high, but not mid, frequency component of the alpha-index compared with sedentary elderly subjects. Some of the age-related changes in baroreflex sensitivity may be related to physical fitness and activity levels.

Adult↗
PubMed1997

Sympathetic reinnervation and heart rate variability after cardiac transplantation.

BACKGROUND: Heart rate variability is thought to measure autonomic modulation, but the relation has never been demonstrated directly in humans. AIM: To test the hypothesis that increased low frequency heart rate variability reflects sympathetic reinnervation after cardiac transplantation. PATIENTS: 24 cardiac transplant recipients at the time of routine surveillance coronary angiography two or more years after cardiac transplantation, and 10 controls with normal coronary arteries undergoing angiography for investigation of chest pain. SETTING: Regional cardiothoracic centre. METHODS: Sympathetic effector function at the sinus node was assessed by measuring the fall in cycle length for two minutes after injection of tyramine to the artery supplying the sinus node. Heart rate variability was measured from three-minute RR interval sequences at rest, during metronomic respiration, and before and after atropine. RESULTS: The logarithm of the low frequency component of heart rate variability during metronomic respiration was linearly related to the logarithm of the change in cycle length after injection of tyramine (R2 = 0.28, P = 0.007). Absolute units more accurately reflected sympathetic effector function than did normalised units or the ratio of low frequency to high frequency. Atropine did not affect high frequency heart rate variability in transplant recipients. CONCLUSIONS: The low frequency component of heart rate variability is directly related to sympathetic reinnervation to the sinus node.

Coronary Angiography↗
PubMed1995

Assessment of the ventricular fibrillation detection algorithm in the semi-automatic Cardio-Aid defibrillator.

The sensitivity and specificity of ventricular fibrillation (VF) detection in the semi-automatic Cardio-Aid defibrillator was assessed with 25 ECG recordings, each of length 40 s. Of the 25 ECG recordings, 12 contained VF requiring defibrillation, 3 contained a tachyarrhythmia with a waveform similar to VF but which self-terminated, and 10 were selected from abnormal rhythms and artefacts which contained some features similar to VF. Sensitivity was assessed from the VF data. Specificity was assessed from both the rhythm preceding VF or the tachyarrhythmias, and from the VF-like data. The response to a changing rhythm was assessed from the self-terminating tachyarrhythmias. Each recording was replayed to the defibrillators at 3 signal amplitudes (normal, half and double). Request to analyse the ECG because of possible VF and advice to shock were noted separately. The sensitivity for recommending a shock when a shock was required was 92%. The sensitivity for drawing attention to VF, through requesting analysis was 97%. There were no false detections in the rhythms preceding VF or the tachyarrhythmias (specificity with good quality signals 100%). The specificity with the VF-like data ws 90%. There was significant difference between this defibrillator and other semi-automated defibrillators previously assessed.

Algorithms↗
PubMed1995

Measurement of baroreflex gain from heart rate and blood pressure spectra: a comparison of spectral estimation techniques.

The baroreflex is the physiological control system linking blood pressure and heart rate. Baroreflex gain, alpha, can be estimated from the ratio of heart rate and blood pressure spectra. The aim of this study was to quantify differences in estimates of alpha incurred by using four different spectral analysis techniques. ECG and blood pressure were recorded from 10 healthy subjects. Spectra were estimated using fast Fourier transform (FFT), zero-padded FFT (FFTZ), FFT of the windowed autocovariance function (ACVF), and maximum-entropy (ME) methods. For each subject a mean value of alpha was calculated in the MF (0.05-0.15 Hz) and HF (0.15-0.35 Hz) bands. Mean alpha MF varied between subjects (range 2-10 ms mmHg-1) as did mean alpha HF (range 4-12 ms mmHg-1). Mean differences in alpha MF and alpha HF estimated with different techniques were small. Differences in alpha MF ranged from 0.074 ms mmHg-1 (FFTZ against ME) to 0.298 ms mmHg-1 (FFT against ACVF) and those in alpha HF ranged from 0.057 ms mmHg-1 (FFT against FFTZ) to 0.342 ms mmHg-1 (ACVF against ME). None of these differences were significant. The use of different spectral analysis techniques does not significantly affect estimates of alpha.

Aged↗
PubMed1995

Objective features of the surface electrocardiogram during ventricular tachyarrhythmias.

The aim of this study was to quantify the electrocardiographic signal characteristics of three types of ventricular arrhythmia; monomorphic ventricular tachycardia, polymorphic ventricular tachycardia and ventricular fibrillation. Patients in a coronary care unit were monitored using a single bipolar ECG lead. Thirty episodes of ventricular tachyarrhythmia (ten from each group) were recorded automatically by computer. Frequency analysis of ten consecutive 1 s epochs from each recording gave 100 spectra for each tachyarrhythmia group. Each spectrum was characterised by the frequency, there were significant differences in all characteristics between the tachyarrhythmia groups (P<0.025). Ventricular fibrillation had a higher mean dominant frequency (4.8 Hz) than polymorphic ventricular tachycardia (3.7 Hz) and monomorphic ventricular tachycardia (3.8 Hz). The dominant frequency of ventricular fibrillation was also more variable than that of monomorphic ventricular tachycardia (P<0.01). Mean peak size was largest for monomorphic ventricular tachycardia (0.78) and smallest for ventricular fibrillation (0.64). The single spectral peaks seen throughout this study indicate that all three tachyarrhythmias have an underlying periodic mechanism. The differences in spectral characteristics show that varying degrees of myocardial electrical organisation can be quantified from surface ECG features.

Electrocardiography↗
PubMed1995

Analysis of the body surface ECG measured in independent leads during ventricular fibrillation in humans.

The degree of myocardial electrical organization during ventricular fibrillation remains unknown. The aim of this study was to compare the characteristics of the surface ECG on three independent and approximately orthogonal leads. Ten recordings of ventricular fibrillation, each induced at electrophysiology study and successfully terminated by direct current shock, were analyzed. Each recording was divided into 1-second epochs for analysis. Frequency analysis using the Fast Fourier Transform showed that the frequency of the dominant spectral peak increased significantly from a mean of 4.1 +/- 0.8 Hz to 5.2 +/- 0.7 Hz during the first 5 seconds of ventricular fibrillation. In 95% of the epochs analyzed, a similar dominant frequency was observed on either two or three ECG leads. Frequency agreement tended to increase as ventricular fibrillation evolved. This study shows that the rate of ventricular fibrillation increases rapidly during the first 5 seconds but only gradually thereafter, and that similar signal characteristics are observed on independent ECG leads. These findings are not compatible with the traditional view of incoherent myocardial activity during ventricular fibrillation.

Body Surface Potential Mapping↗
PubMed1995

Evidence for electrical organization during ventricular fibrillation in the human heart.

INTRODUCTION: Ventricular fibrillation is a most dangerous cardiac arrhythmia that has received considerable attention, yet its pattern of electrical activation remains controversial. The aim of this study was to investigate the degree of organization during the clinical arrhythmia and to examine the phase relationship between deflections in independent ECG leads. METHODS AND RESULTS: Ten recordings of ventricular fibrillation were examined. Each had been provoked during routine electrophysiological study. The mean duration of ventricular fibrillation was 21 seconds (range 11 to 34). Independent and approximately orthogonal ECG leads I, aVF, and V2 were recorded to computer at a sampling rate of 250 Hz. The phase relationship of each ECG lead pair was measured from the lag of peaks in their cross-correlation function (CCF). In 61% of the 1-second ECG epochs analyzed, CCF peak lag changed by < 20 msec compared to the previous epoch. Thus, the overall phase relationship was stable most of the time. Changes in CCF peak lag tended to be either gradual or to punctuate periods of stability. CONCLUSIONS: This study provides evidence of organized myocardial activation during human ventricular fibrillation.

Electrocardiography↗
PubMed1994

Simplified body-surface electrocardiographic maps with depolarization magnitude and direction.

A new technique is presented for extracting the magnitude and direction of ventricular depolarization at the body surface from surface electrocardiographic (ECG) map data. Bipolar electrocardiograms were obtained from 36 sites on the chest surface in five normal subjects. The direction and magnitude of depolarization as seen from the chest surface were calculated for 18 body-surface areas centred between electrode positions V1 and V6. Each area was bounded by three electrodes with an electrode spacing of 5 cm. A major depolarization component could be calculated for all triangular areas, with 48% of areas having a smaller second component. The area with the greatest magnitude in each subject had a depolarization vector pointing downwards and to the left, with an average angle to the horizontal of 55 degrees. This was consistent with an average angle of 51 degrees obtained from the subjects' 12-lead electrocardiograms. There was more variability in vector angle between adjacent areas on the right-hand side. At the V5/V6 areas, close to the cardiac apex, the vector component had an upwards orientation in all subjects, opposing the overall downward component of ventricular depolarization. The technique was able to determine local depolarization directions which were in agreement with the normal cardiac vector derived from standard electrocardiography. Reversal of the vector direction close to the cardiac apex and the collision of depolarization components from different directions could be detected. This simple form of body-surface mapping can reduce the essential features of depolarization to a single map, and provide information not directly available from a 12-lead electrocardiogram.

Adult↗