Monitoring of Caffeine Consumption Effect on Skin Blood Properties by Diffuse Reflectance Spectroscopy.

Caffeine is the most widely consumed psychoactive substance worldwide, affecting numerous tissues and organs, with notable impacts on the central nervous system, heart, and blood vessels. The effect of caffeine on vascular smooth muscle cells is an initial transient contraction followed by significant vasodilatation. In this study we investigate the use of diffuse reflectance spectroscopy (DRS) for monitoring of vascular changes in human skin induced by caffeine consumption. DRS spectra were recorded on volar sides of the forearms of eight healthy volunteers at time intervals of 0, 30, 60, 120, and 180 min after consumption of caffeine, while one subject served as a negative control. Analytical diffusion approximation solutions for diffuse reflectance from three-layer structures were used to assess skin composition (e.g. dermal blood volume fraction and oxygen saturation) by fitting these solutions to experimental data. The results demonstrate that cutaneous vasodynamics induced by caffeine consumption can be monitored by DRS, while changes in the control subject not consuming caffeine were insignificant.

Organization of ventricular fibrillation in the human heart: experiments and models.

Sudden cardiac death is a major health problem in the industrialized world. The lethal event is typically ventricular fibrillation (VF), during which the co-ordinated regular contraction of the heart is overthrown by a state of mechanical and electrical anarchy. Understanding the excitation patterns that sustain VF is important in order to identify potential therapeutic targets. In this paper, we studied the organization of human VF by combining clinical recordings of electrical excitation patterns on the epicardial surface during in vivo human VF with simulations of VF in an anatomically and electrophysiologically detailed computational model of the human ventricles. We find both in the computational studies and in the clinical recordings that epicardial surface excitation patterns during VF contain around six rotors. Based on results from the simulated three-dimensional excitation patterns during VF, which show that the total number of electrical sources is 1.4 +/- 0.12 times greater than the number of epicardial rotors, we estimate that the total number of sources present during clinically recorded VF is 9.0 +/- 2.6. This number is approximately fivefold fewer compared with that observed during VF in dog and pig hearts, which are of comparable size to human hearts. We explain this difference by considering differences in action potential duration dynamics across these species. The simpler spatial organization of human VF has important implications for treatment and prevention of this dangerous arrhythmia. Moreover, our findings underline the need for integrated research, in which human-based clinical and computational studies complement animal research.

A computational study of mother rotor VF in the human ventricles.

Sudden cardiac death is one of the major causes of death in the industrialized world. It is most often caused by a cardiac arrhythmia called ventricular fibrillation (VF). Despite its large social and economical impact, the mechanisms for VF in the human heart yet remain to be identified. Two of the most frequently discussed mechanisms observed in experiments with animal hearts are the multiple wavelet and mother rotor hypotheses. Most recordings of VF in animal hearts are consistent with the multiple wavelet mechanism. However, in animal hearts, mother rotor fibrillation has also been observed. For both multiple wavelet and mother rotor VF, cardiac heterogeneity plays an important role. Clinical data of action potential restitution measured from the surface of human hearts have been recently published. These in vivo data show a substantial degree of spatial heterogeneity. Using these clinical restitution data, we studied the dynamics of VF in the human heart using a heterogeneous computational model of human ventricles. We hypothesized that this observed heterogeneity can serve as a substrate for mother rotor fibrillation. We found that, based on these data, mother rotor VF can occur in the human heart and that ablation of the mother rotor terminates VF. Furthermore, we found that both mother rotor and multiple wavelet VF can occur in the same heart depending on the initial conditions at the onset of VF. We studied the organization of these two types of VF in terms of filament numbers, excitation periods, and frequency domains. We conclude that mother rotor fibrillation is a possible mechanism in the human heart.

Effect of heterogeneous APD restitution on VF organization in a model of the human ventricles.

The onset of ventricular fibrillation (VF) has been associated with steep action potential duration restitution in both clinical and computational studies. Recently, detailed clinical restitution properties in cardiac patients were reported showing a substantial degree of heterogeneity in restitution slopes at the epicardium of the ventricles. The aim of the present study was to investigate the effect of heterogeneous restitution properties in a three-dimensional model of the ventricles using these clinically measured restitution data. We used a realistic model of the human ventricles, including detailed descriptions of cell electrophysiology, ventricular anatomy, and fiber direction anisotropy. We extended this model by mapping the clinically observed epicardial restitution data to our anatomic representation using a diffusion-based algorithm. Restitution properties were then fitted by regionally varying parameters of the electrophysiological model. We studied the effects of restitution heterogeneity on the organization of VF by analyzing filaments and the distributions of excitation periods. We found that the number of filaments and the excitation periods were both dependent on the extent of heterogeneity. An increased level of heterogeneity leads to a greater number of filaments and a broader distribution of excitation periods, thereby increasing the complexity and dynamics of VF. Restitution heterogeneity may play an important role in providing a substrate for cardiac arrhythmias.

The effect of nontransmural necroses on epicardial potential maps during paced activation: a simulation study.

A number of studies have indicated that epicardial potentials provide detailed spatiotemporal information about the spread of electrical activation within the ventricular wall. Here, we used a computer model to simulate activation sequences and corresponding epicardial potential maps in the ventricles damaged by localized necroses. Our findings agreed with those of experimental studies performed for epicardial pacing locus in a complete transient loss of one of the positive areas when the necrosis was located subepicardially, and in a transient gap in the expanding positive areas when the necrosis was located intramurally and subendocardially. This study--by systematically comparing simulated epicardial potential maps with those recorded on the exposed canine hearts--constitutes an important step in validation of our model.

Value and limitations of an inverse solution for two equivalent dipoles in localising dual accessory pathways.

Investigations were carried out into whether an equivalent generator consisting of two dipoles could be used to detect dual sites of ventricular activity. A computer model of the human ventricular myocardium was used to simulate activation sequences initiated at eight different pairs of sites positioned on the epicardial surface of the atrio-ventricular ring. From these sequences, 117-lead body surface potentials (covering the anterior and posterior torso), 64-lead magnetic field maps (above the anterior chest) and 128-lead magnetic field maps (above the anterior and posterior chest) were simulated and were then used to localise dual accessory pathways employing pairs of equivalent dipoles. Average localisation errors were 12 mm, 12 mm and 9 mm, respectively, when body surface potentials, 64-lead and 128-lead magnetic fields were used. The results of the study suggest that solving the inverse problem for two dipoles could provide additional information on dual accessory pathways prior to electrophysiological study.

Noninvasive characterisation of multiple ventricular events using electrocardiographic imaging.

Distributions of epicardial potentials, calculated from body surface electrocardiograms (ECGs), were investigated to determine if they could enable detection of multiple sites of ventricular activity. An anatomical model of the human ventricular myocardium was used to simulate activation sequences initiated at nine different ventricular pairs of sites. From these sequences, body surface ECGs were simulated at 352 sites on the torso surface and then used to reconstruct epicardial potentials at 202 sites. The criterion for detection of dual ventricular events was the presence of two distinct primary potential minima in the reconstructed epicardial potentials. The shortest distance between the two events in the right ventricle that resulted in the reconstruction of epicardial potential patterns, featuring two minima, was 27 mm; the distance between the two events in the left ventricle was 23 mm. When Gaussian white noise in the simulated body surface potentials was increased from 3 microV to 15 microV and 50 microV, dual events became more difficult to distinguish. Findings indicate that calculated epicardial potentials provide useful visual information about the presence of multiple ventricular events that is not apparent in features of body surface ECGs, and could be particularly helpful in optimising mapping procedures during difficult or unsuccessful radiofrequency ablations of accessory pathways.

Spatial resolution of epicardial pace mapping using body surface potentials.

Body surface potential maps (BSPMs) recorded during pace mapping provide an important non-invasive means for identifying local cardiac events; recent clinical studies demonstrated that endocardial pacing sites can be resolved within less than 10 mm. We sought to determine whether similar spatial resolution could be achieved during epicardial pacing. Four patients who were undergoing either heart valve replacement (one), aortocoronary bypass graft (one), or both (two) were studied. In each patient, a pair of epicardial electrodes was placed intraoperatively at the middle aspect of the right ventricular free wall. The distance between the neighbouring electrodes was 10 mm. Five days after the surgery, ECGs were acquired from 35 leads during pacing from each epicardial electrode. We determined the distributions of QRS integrals (the net area under the ECG signal) and compared integrals corresponding to pacing from each of the adjacent electrodes using statistical indices. Student's t-test was applied to these indices and in all the patients revealed that differences in distributions of QRS integral maps were statistically significant (p < 0.01). Results of our study indicate that the non-invasive acquisition of body surface ECGs could resolve epicardial breakthrough sites within 10 mm, which may be useful in facilitating therapeutic ablations in patients with ventricular tachycardias.

Electrocardiographic imaging.

Electrocardiographic imaging (ECGI) is a useful noninvasive modality for exploring the spread of electrical activation within the ventricular wall. In this model study, we seek to determine whether ECGI could detect changes in patterns of pacing-generated epicardial potentials. An anatomical model of the human ventricular myocardium is used to simulate activation sequences initiated at 116 endocardial pacing sites distributed over the left ventricular free wall. From these realistic sequences, we simulate extracardiac potentials at epicardial (202 sites) and torso surfaces (352 sites) using boundary element model of the human torso. ECGI is applied to compute epicardial potentials and unipolar electrograms (202 sites). Inversely computed electrograms correlate well with those simulated by an anatomical model (r>0.9 at 71% of sites). Features of the calculated epicardial potential patterns provide direct visual information about the site of pacing. The results also demonstrate that ECGI provides detailed spatio-temporal reconstruction of patterns of myocardial activation.

Value of magnetocardiographic QRST integral maps in the identification of patients at risk of ventricular arrhythmias.

It has been shown that regional ventricular repolarization properties can be reflected in body surface distributions of electrocardiographic QRST deflection areas (integrals). We hypothesize that these properties can be reflected also in the magnetocardiographic QRST areas and that this may be useful for predicting vulnerability to ventricular tachyarrhythmias. Magnetic field maps were obtained during sinus rhythm from 49 leads above the anterior chest in 22 healthy (asymptomatic) control subjects (group A) and in 29 patients with ventricular arrhythmias (group B). In each subject, the QRST deflection area was calculated for each lead and displayed as an integral map. The mean value of maximum was significantly larger in the control group A than in the patient group B (1,626+/-694 pTms vs. 582+/-547 pTms, P<0.0001). To quantitatively assess intragroup variability in the control group A and intergroup variability of the control and patient groups, we used the correlation coefficient r and covariance sigma. These indices showed significantly less intragroup than intergroup variation (e.g., in terms of sigma, 28.0x10(-6)+/-12.3x10(-6) vs. 3.4x10(-6)+/-12.5x10(-6), P<0.0001). Each QRST integral map was also represented as a weighted sum of 24 basis functions (eigenvectors) by means of Karhunen-Loeve transformation to calculate the contribution of the nondipolar eigenvectors (all eigenvectors beyond the third). This percentage nondipolar content of magnetocardiographic QRST integral maps was significantly higher in the patient group B than in the control group A (13.0%+/-9.1 % vs. 2.6%+/-2.0%, P<0.0001). Discriminations between control subjects and patients with ventricular arrhythmias based on magnitude of the maximum, covariance sigma, and nondipolar content were 90.2%, 90.2%, and 86.3% accurate, with a sensitivity of 89.7%, 93.1%, and 75.9%, and a specificity of 90.9%, 86.4%, and 100%. We have shown that magnitude of the maximum and indices of variability and nondipolarity of the magnetocardiographic QRST integral maps may predict arrhythmia vulnerability. This finding is in agreement with earlier studies that used body surface potential mapping and suggests that magneticfield mapping may also be a useful diagnostic tool for risk analysis.

Localization of intramural necrotic regions using electrocardiographic imaging.

Recent studies have demonstrated that electrocardiographic imaging (ECGI) is a novel noninvasive modality for exploring the spread of electrical activation within the ventricular wall. In this study, our goal was to explore the ability of ECGI in reconstructing epicardial potentials and electrograms in the ventricles damaged by localized necroses (<2 cm2). An anatomical model of the human ventricular myocardium was used to simulate activation sequences initiated at 428 epicardial and endocardial pacing sites distributed over the right ventricular and left ventricular free walls. From these realistic sequences, we simulated extracardiac potentials at epicardial (202 sites) and torso surfaces (352 sites) using boundary element model of the human torso. ECGI in terms of the L-curve was applied to compute epicardial potentials and unipolar electrograms (202 sites). Inversely computed electrograms correlated well with those simulated by an anatomical model (r > 0.9 at 68% of sites). Specifically, ECGI accurately reconstructed the following features that have been observed during measurements on the exposed canine hearts: (a) an epicardial potential pattern with a central minimum and two maxima, with the minimum positioned above the pacing site; (b) a complete transient loss of one of the positive areas in the epicardial potential pattern when the necrosis was located subepicardially; and (c) a transient gap in the expanding positive areas of the epicardial potential pattern when the necrosis was located intramurally or subendocardially. Findings of our study indicate that ECGI provides detailed reconstruction of patterns of myocardial activation in the presence of localized necroses and may be useful in the assessment of arrhythmogenic substrate in the clinical setting.

Assessment of spatial resolution of pace mapping when using body surface potentials.

Using computer simulations and statistical methods, the resolution of pace mapping when used in combination with body surface potentials was systematically investigated. In an anatomical model of the human ventricular myocardium, pre-excitation sequences were initiated at 69 sites positioned along the atrioventricular (AV) ring and corresponding body surface potential maps (BSPMs) were calculated at 32 leads placed on the anterior torso. For each time after the onset of pre-excitation (every 4 ms to 40 ms) and each root-mean-square (RMS) noise level (5, 10, 20 and 50 microV), BSPMs were cros-correlated and the spatial resolution defined as the largest pacing site separation at which the differences in correlation coefficients were not statistically significant (level p > or = 0.05). The findings indicate that when random RMS noise of 5 microV was added to the simulated BSPMs, average spatial resolution over all 60 sites was at 20 ms after the onset of pre-excitation within 3.5 +/- 0.9 mm. The results provide theoretical evidence that statistical analysis of BSPMs obtained during pace mapping can offer improved means for subcentimetre identification of accessory pathways located along the AV ring.

Simulated epicardial potential maps during paced activation reflect myocardial fibrous structure.

Using a three-dimensional propagation model of the human ventricular myocardium, we studied the role of fibrous structure in generating epicardial potential maps. This model represents the myocardium as an anisotropic bidomain with an equal anisotropy ratio, and it incorporates a realistic representation of anatomical features, including epi-endocardial fiber rotation in the compact portion of the wall (compacta) and a distinct fiber arrangement of the trabeculated portion (trabeculata). Activation sequences were elicited at various intramural depths, and maps were calculated throughout a 60 ms sequence. The simulated maps closely resembled those measured by others in the canine heart. During the early stages of activation, a typical map featuring a central minimum flanked by two maxima emerged, with the axis joining these extrema approximately parallel to the fibers near the pacing site, and the axis joining the maxima rotated in the same direction as the fibers for different pacing depths; for endocardial and subendocardial pacing this map changed into one with an oblong positive area. During the later stages of activation, the positive areas of the maps expanded and rotated with the transmural fiber rotation. In concurrence with experiments, we saw a fragmentation and asymmetry of expanding and rotating positive areas. The latter features-apparently caused by the interface between the compacta and trabeculata, variable local thickness of the wall, or local undulations of the vetricular surface-could not be reproduced by more idealized, slab models.

Accuracy of single-dipole inverse solution when localising ventricular pre-excitation sites: simulation study.

Different factors are investigated that may affect the accuracy of an inverse solution that uses a single-dipole equivalent generator, in a standardised inhomogeneous torso model, when localising the pre-excitation sites. An anatomical model of the human ventricular myocardium is used to simulate body surface potential maps (BSPMs) and magnetic field maps (MFMs) for 35 pre-excitation sites positioned on the epicardial surface along the atrioventricular ring. The sites of pre-excitation activity are estimated by the single-dipole method, and the measure for the accuracy of the localisation is the localisation error, defined as the distance between the location of the best-fitting single dipole and the actual site of pre-excitation in the ventricular model. The findings indicate that, when the electrical properties of the volume conductor and lead positions are precisely known and the 'measurement' noise is added to the simulated BSPMs and MFMs, the single-dipole method optimally localises the pre-excitation activity 20 ms after the onset of pre-excitation, within 0.71 +/- 0.28 cm and 0.65 +/- 0.30 cm using BSPMs and MFMs, respectively. When the standard torso model is used to localise the sites of onset of the pre-excitation sequence initiated in four individualised torso models, the maximum errors are as high as 2.6-3.0 cm (even though the average error, for both the BSPM and MFM localisations, remains within the 1.0-1.5 cm range). In spite of these shortcomings, it is thought that single-dipole localisations can be useful for non-invasive pre-interventional planning.