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At least 919 records · Page 51Linked to original sources
PubMed2003

Voronoi polyhedra analysis of optimized arterial tree models.

Topological and metric properties of Voronoi polyhedra (VP) generated by the distal end points of terminal segments in arterial tree models grown by the method of constrained constructive optimization (CCO) are analyzed with the aim to characterize the spatial distribution of their supply sites relative to randomly distributed points as a reference model. The distributions of the number Nf of Voronoi cell faces, cell volume V, surface area S, area A of individual cell faces, and asphericity parameter alpha of the CCO models are all significantly different from the ones of random points, whereas the distributions of V, S, and alpha are also significantly different among CCO models optimized for minimum intravascular volume and minimum segment length (p < 0.0001). The distributions of Nf, V, and S of the CCO models are reasonably well approximated by two-parameter gamma distributions. We study scaling of intravascular blood volume and arterial cross-sectional area with the volume of supplied tissue, the latter being represented by the VP of the respective terminal segments. We observe scaling exponents from 1.20 +/- 0.007 to 1.08 +/- 0.005 for intravascular blood volume and 0.77 +/- 0.01 for arterial cross-sectional area. Setting terminal flows proportional to the associated VP volumes during tree construction yields a relative dispersion of terminal flows of 37% and a coefficient of skewness of 1.12.

Algorithms↗
PubMed2003

Homogeneity of cardiac contraction despite physiological asynchrony of depolarization: a model study.

The use of mathematical models combining wave propagation and wall mechanics may provide new insights in the interpretation of cardiac deformation toward various forms of cardiac pathology. In the present study we investigated whether combining accepted mechanisms on propagation of the depolarization wave, time variant mechanical properties of cardiac tissue after depolarization, and hemodynamic load of the left ventricle (LV) by the aortic impedance in a three-dimensional finite element model results in a physiological pattern of cardiac contraction. We assumed that the delay between depolarization for all myocytes and the onset of crossbridge formation was constant. Two simulations were performed, one in which contraction was initiated according to the regular depolarization pattern (NORM simulation), and another in which contraction was initiated after synchronous depolarization (SYNC simulation). In the NORM simulation propagation of depolarization was physiological, but wall strain was unphysiologically inhomogeneous. When simulating LV mechanics with unphysiological synchronous depolarization (SYNC) myofiber strain was more homogeneous and more physiologic. Apparently, the assumption of a constant delay between depolarization and onset of crossbridge formation results in an unrealistic contraction pattern. The present finding may indicate that electromechanical delay times are heterogeneously distributed, such that a contraction in a normal heart is more synchronous than depolarization.

Anisotropy↗
PubMed2003

A single equivalent moving dipole model: an efficient approach for localizing sites of origin of ventricular electrical activation.

We propose a new method for guiding catheter ablation procedures to abolish sites of origin of arrhythmias. This method models both cardiac electrical activity and current pulses delivered from the tip of the ablation catheter with a single equivalent moving dipole (SEMD). The SEMD parameters are obtained from analysis of body surface potentials. In this paper we examine the feasibility of this method by evaluating the performance of an inverse algorithm we developed to localize the SEMD from the surface potentials. In computer simulations realistic levels of measurement noise led to uncertainties in SEMD location approximately 0.005 cm. Dipole orientation randomization contributed to increased uncertainty (0.04 cm) in SEMD location only when boundary effects were included. In ventricular pacing swine studies, we found that the SEMD model accurately accounted for electrocardiographic wave forms and that measurement noise led to an uncertainty of approximately 0.04 cm in the SEMD at 15 ms after the pacing spike. We have also found that the algorithm we developed to identify the SEMD parameters yielded positions for two spatially separated pacing sites that maintained their direction and were very close to their physical separation. These results suggest that the SEMD method may potentially be used to guide radio-frequency ablation procedures.

Action Potentials↗
PubMedDate not supplied

Analysis of electrically induced reentrant circuits in a sheet of myocardium.

Understanding the complex spatiotemporal dynamics of action potential propagation in the heart during arrhythmia is exceedingly difficult. This study applies nonlinear dynamics tools to simplify this task. Using the results of a simulation of an electrical induction of reentry in a sheet of myocardium represented as a bidomain, transmembrane voltage maps are processed to obtain: (i) spatial maps of phase angle and phase singularity trajectories, (ii) state scatter plots, and (iii) spatial maps of even phase resetting, wave fronts and wave tails. Tracking the phase singularities allows us to identify the "seeds" of reentry before the reentrant circuit is formed and to characterize the spatiotemporal evolution of the organizing center of the reentrant circuit. The state scatter plots demonstrate the effect of the shock on the instantaneous state of the system. The spatial maps of even phase resetting allow us to identify the shock-induced excitable gaps (regions of regenerative repolarization) as well as the regions directly activated by the shock. These nontraditional approaches to the analysis of electrophysiological phenomena greatly enhance our ability to conceptualize the dynamics of arrhythmias.

Action Potentials↗
PubMedDate not supplied

Effect of variation in intraluminal thrombus constitutive properties on abdominal aortic aneurysm wall stress.

The abdominal aortic aneurysm (AAA) is a degenerating disease for which the end stage is the rupture of the vessel wall. Accurate prediction of the stresses acting on the aneurysm tissue may be used to determine the actual risk of rupture of a specific aneurysm. To accomplish this, a correct constitutive model for the aneurysmal aortic wall and any intraluminal thrombus (ILT) present within it are needed. Our laboratory has previously reported the mechanical properties of ILT. The aim of this work is to investigate the reliability of using population-mean values of ILT constitutive parameters to estimate AAA wall stress distribution. For this, a three-dimensional asymmetric model of an aneurysm including ILT was generated and a parametric study was conducted varying ILT constitutive properties within a physiological range. Results show that the presence of any ILT reduces and redistributes the stresses in the aortic wall markedly. Maximum variation in the peak wall stresses for all the models analyzed was 5%. Adopting a nonhomogeneous ILT did not alter the stress distribution. On the basis of these results, we infer that population mean parameters for ILT material characteristics can be used to reasonably estimate the wall stresses in patient specific aneurysm models.

Aorta, Abdominal↗
PubMed2003

Noninvasive electrocardiographic imaging (ECGI): application of the generalized minimal residual (GMRes) method.

Electrocardiographic imaging (ECGI) is a developing imaging modality for cardiac electrophysiology and arrhythmias. It reconstructs epicardial potentials, electrograms, and isochrones from electrocardiographic body-surface potentials noninvasively. Current ECGI methodology employs Tikhonov regularization, which imposes constraints on the reconstructed potentials or their derivatives. This approach can sometimes reduce spatial resolution by smoothing the solution. Accuracy depends on a priori knowledge of solution characteristics and determination of an optimal regularization parameter. These properties led us to implement an independent, iterative approach for ECGI--the generalized minimal residual (GMRes) method--which does not apply constraints. GMRes was applied to experimental data during activation/repolarization of normal and infarcted hearts. GMRes reconstructions were compared to Tikhonov reconstructions and to measured "gold standards" in isolated hearts. Overall, the accuracy of GMRes solutions was similar to Tikhonov regularization. However, in certain cases GMRes recovered localized potential features (e.g., multiple potential minima), which were lost in the Tikhonov solution. Simultaneous use of these two complementary methods in clinical ECGI will ensure reliability and maximal extraction of diagnostic information in the absence of a priori information about a patient's condition.

Action Potentials↗
PubMed2003

Use of cardiac electric near-field measurements to determine activation times.

In a recent paper, we described the behavior of the cardiac electric near-field, E, parallel to the tissue surface during continuous conduction. We found that T(E), the time at which the peak near-field, E, occurs, is an accurate marker of local activation time. Examination of experimentally recorded E vector loops revealed a large variety of morphologies. We postulated that propagation around an obstacle could lead to the observed deviations in loop morphology. The purpose of this study was to determine if this was plausible, and if so, whether T(E) remains an accurate time marker of local activation under these conditions. We used a monodomain computer model of a sheet of cardiac tissue with a central conduction obstacle immersed in an unbounded volume conductor. Activation times T(Im), T(phi), and T(E) were derived from the transmembrane current I(m), the extracellular potential phi(e), and E, respectively. The obstacle led to deformations of the vector loops, morphologically similar to those observed experimentally, particularly during the initial and terminal phases, and to a lesser degree near the time of E. Despite these loop deformations, T(E) was an accurate time marker of local activation. We found that T(E) was significantly closer to T(Im) than T(phi). We concluded that isochrone maps computed from T(E) better reflect intracellular activation patterns than those computed from T(phi). For a given electrode spacing of 60 microm, the sensitivity to noise of E was significantly less than that of phi(e). Hence, T(E) was less affected by noise than T(phi).

Animals↗
PubMed2003

Cardiac near-field morphology during conduction around a microscopic obstacle--a computer simulation study.

In a recent paper, we described the behavior of the cardiac electric near-field, E, parallel to the tissue surface during continuous conduction. We found that the tip of E describes a vector-loop during depolarization with the peak field, E, pointing opposite to the direction of propagation, phiI(m). Experimentally recorded loop morphologies of E, however, frequently showed significant deviations from the theoretically predicted behavior. We hypothesized that this variety of morphologies might be caused by conduction obstacles at a microscopic size scale. This study examines the influence of obstacles on the morphology of vector loops of E and whether the peak of distorted loops remains a reliable indicator for the direction of propagation. We used a computer model of a sheet of cardiac tissue with a central conduction obstacle immersed in an unbounded volume conductor. We studied the loop morphologies of E and the differences between the intracellularly determined direction of propagation, phiI(m), and the direction of E, phiE. Distortions of the vector loop were morphologically similar to those observed experimentally. Differences between phiI(m) and phiE were less than 18 degrees at all observation sites. The obstacle led to deformations of the loop morphology, particularly during the initial and terminal phases, and to a lesser degree near the instant of E. We concluded that E is a reliable indicator of phiI(m).

Animals↗
PubMed2003

Ion channel basis for alternans and memory in cardiac myocytes.

Beat-to-beat alternation in action potential morphology (alternans) in individual cardiac cells may be important in the development of ventricular tachycardia and fibrillation. So far, it has been difficult to identify the cause for alternans at the ion channel level because computer models and experiments that display alternans also simultaneously exhibit other confounding rhythm patterns, including those attributable to short timescale memory effects. To address this difficulty, we have developed an eigenmode method to study the dynamics of detailed cardiac cell models under constant pacing. The method completely separates these effects from one another in the linear regime, allowing each to be studied individually. For the Beeler-Reuter ion channel model, the fundamental difference between the alternans and memory modes was found to be rooted in the difference in the relative phasings of the x1 and f gate perturbations associated with the slow outward and slow inward currents, respectively. The importance of this relative phasing was analyzed with the help of two new analytical methods. For the alternans case, the relative phasing produced constructive interference between the two currents large enough to reverse the perturbation in membrane potential from beat to beat. The opposite was true of the memory mode.

Action Potentials↗
PubMedDate not supplied

Hemodynamic effect of cerebral vasospasm in humans: a modeling study.

A mathematical model of cerebral hemodynamics during vasospasm is presented. The model divides arterial hemodynamics into two cerebral territories: with and without spasm. It also includes collateral circulation between the two territories, cerebral venous hemodynamics, cerebrospinal fluid circulation, intracranial pressure (ICP) and the craniospinal storage capacity. Moreover, the pial artery circulation in both territories is affected by cerebral blood flow (CBF) autoregulation mechanisms. In this work, a numerical value to model parameters was given assuming that vasospasm affects only a single middle cerebral artery (MCA). In a first stage, the model is used to simulate some clinical results reported in the literature, concerning the patterns of MCA velocity, CBF and pressure losses during vasospasm. The agreement with clinical data turns out fairly good. In a second stage, a sensitivity analysis on some model parameters is performed (severity of caliber reduction, longitudinal extension of the spasm, autoregulation gain, ICP, resistance of the collateral circulation, and mean systemic arterial pressure) to clarify their influence on hemodynamics in the spastic territory. The results suggest that the clinical impact of vasospasm depends on several concomitant factors, which should be simultaneously taken into account to reach a proper diagnosis. In particular, while a negative correlation between MCA velocity and cross sectional area can be found until CBF is well preserved, a positive correlation may occur when CBF starts to decrease significantly. This might induce false-negative results if vasospasm is assessed merely through velocity measurements performed by the transcranial Doppler technique.

Blood Flow Velocity↗
PubMedDate not supplied

Theoretical study of the effects of vascular smooth muscle contraction on strain and stress distributions in arteries.

To study the effects of smooth muscle contraction and relaxation on the strain and stress distribution in the vascular wall, a mathematical model was proposed. The artery was assumed to be a thick-walled orthotropic tube made of nonlinear, incompressible elastic material. Considering that the contraction of smooth muscle generates an active circumferential stress in the wall, a numerical study was performed using data available in the literature. The results obtained showed that smooth muscle contraction affects the residual strains which exist in a ring segment cut out from the artery and exposed to no external load. When the ring specimen is cut radially, it springs open with an opening angle. The predicted monotonic increase of the opening angle with increasing muscular tone was in agreement with recent experimental results reported in the literature. It was shown that basal muscular tone, which exists under physiological conditions, reduces the strain gradient in the arterial wall and yields a near uniform stress distribution. During temporary changes in blood pressure, the increase in muscular tone induced by elevated pressure tends to restore the distribution of circumferential strain in the arterial wall, and to maintain the flow-induced wall shear stress to normal level.

Animals↗
PubMedDate not supplied

In vivo three-dimensional surface geometry of abdominal aortic aneurysms.

Abdominal aortic aneurysm (AAA) is a local, progressive dilation of the distal aorta that risks rupture until treated. Using the law of Laplace, in vivo assessment of AAA surface geometry could identify regions of high wall tensions as well as provide critical dimensional and shape data for customized endoluminal stent grafts. In this study, six patients with AAA underwent spiral computed tomography imaging and the inner wall of each AAA was identified, digitized, and reconstructed. A biquadric surface patch technique was used to compute the local principal curvatures, which required no assumptions regarding axisymmetry or other shape characteristics of the AAA surface. The spatial distribution of AAA principal curvatures demonstrated substantial axial asymmetry, and included adjacent elliptical and hyperbolic regions. To determine how much the curvature spatial distributions were dependent on tortuosity versus bulging, the effects of AAA tortuosity were removed from the three-dimensional (3D) reconstructions by aligning the centroids of each digitized contour to the z axis. The spatial distribution of principal curvatures of the modified 3D reconstructions were found to be largely axisymmetric, suggesting that much of the surface geometric asymmetry is due to AAA bending. On average, AAA surface area increased by 56% and abdominal aortic length increased by 27% over those for the normal aorta. Our results indicate that AAA surface geometry is highly complex and cannot be simulated by simple axisymmetric models, and suggests an equally complex wall stress distribution.

Aorta, Abdominal↗
PubMedDate not supplied

The role of G-proteins in the regulation of pacemaking activity.

This work is concerned with modeling the key interrelated biochemical reactions involved in initiating and inhibiting pacemaking activity in the mammalian sinoatrial node. A detailed model involving G-proteins was developed to better represent the activation pathway for adenylate cyclase. Concentration profiles of an activated G-protein complex [alpha(T)C] were established as a function of the membrane bound calcium calmodulin concentration. A previously developed model used to establish temporal profiles of cAMP was improved using the G-protein effects through the [alpha(T)C] functionality. Methods were also developed to model inhibition of G-protein by acetylcholine. Analytical solutions were developed to predict acetylcholine concentration profiles as a function of diffusion parameter and duration of acetylcholine pulses. The model was used to demonstrate suppression of cAMP by acetylcholine through G-protein pathways. It provides a basis for a tool to quantify key biochemical species during stimulation and inhibition of sinoatrial node pacemaking. A stability analysis of the model equations has potential application in studying the link between the biochemical species concentrations and abnormal effects in sinoatrial node pacemaking.

Acetylcholine↗
PubMed2004

Influence of progressive central hypovolemia on Hölder exponent distributions of cardiac interbeat intervals.

The purpose of the study was to determine the dependency of the statistical properties of the R to R interval (RRI) time series on progressive central hypovolemia with lower body negative pressure. Two data-processing techniques based on wavelet transforms were used to determine the change in the nonstationary nature of the RRI time series with changing negative pressure. The results suggest that autonomic neural mechanism driving cardiac interbeat intervals during central hypovolemia go through various levels of multifractality, as determined by Hölder exponent distributions.

Adaptation, Physiological↗
PubMed2004

Cooperativity between selectins and beta2-integrins define neutrophil capture and stable adhesion in shear flow.

A cooperative, sequential process of molecular recognition governs leukocyte capture, rolling, and arrest on inflamed endothelium. Flowing neutrophils are captured via heterotypic adhesive interactions mediated by endothelial E-selectin, whereas homotypic interactions between neutrophils are mediated by L-selectin. To elucidate how each selectin facilitates the transition to CD18-mediated stable adhesion, E-selectin and L-selectin were expressed at defined site density in a murine pre-B-cell line. Direct observation of two-body collisions revealed that 30% of neutrophil interactions with E-selectin transfectants formed doublets at low shear rate G = 14 s(-1) whereas a threshold shear rate 14 s(-1) < or = G < or = 10 s(-1) was necessary for L-selectin adhesion. Adhesion via L-selectin resisted rupture at high shear stress, while E-selectin tethered doublets remained intact longer once formed. Moreover, higher expression of L-selectin (1100 sites/microm2) than that of E-selectin (220 sites/microm2) was required for comparable heterotypic adhesion efficiency. With a threefold rise in active CD18 upregulated on chemotactically stimulated neutrophils, homotypic adhesion efficiency increased 10-fold compared to less than 5-fold for heterotypic adhesion to selectin transfectants. Co-expression of E-selectin and ICAM-1 boosted adhesion efficiency threefold more than either receptor alone over the range of active CD18 expression. These data are the first to quantify adhesion efficiency mediated by selectin tethering and conformational activation of beta2-integrin in neutrophils in shear flow.

Animals↗
PubMed2004

Assessment of chaotic parameters in nonstationary electrocardiograms by use of empirical mode decomposition.

This study addressed the issue of assessing chaotic parameters from nonstationary electrocardiogram (ECG) signals. The empirical mode decomposition (EMD) was proposed as a method to extract intrinsic mode functions (IMFs) from ECG signals. Chaos analysis methods were then applied to the stationary IMFs without violating the underlying assumption of stationarity. Eight ECG data sets representing normal and various abnormal rhythms were obtained from the American Heart Associate Ventricular Arrhythmia database. The chaotic parameters including Lyapunov exponent, entropy, and correlation dimension were computed. The results consistently showed that the 10th IMF (IMF-10) was stationary and preserved sufficient nonlinearity of the ECG signals. Each IMF-10 from the data sets (n = 8) gave a positive dominate Lyapunov exponent (0.29-0.64, p < 0.0001), a positive entropy (0.039-0.061, p < 0.0001), and a noninteger correlation dimension (1.1-1.9). These were evidences of a chaotic dynamic system. We therefore concluded that the original ECG signals must also have chaotic properties. The chaotic parameters did not show significant differences among the eight data sets representing normal sinus rhythm and various abnormalities. This study has demonstrated an effective way to characterize nonlinearities in nonstationary ECG signals by combining the empirical mode decomposition and the chaos analysis methods.

Algorithms↗
PubMed2006

Statistical hemodynamics: a tool for evaluating the effect of fluid dynamic forces on vascular biology in vivo.

BACKGROUND: In vivo experimentation is the most realistic approach for exploring the vascular biological response to the hemodynamic stresses that are present in life. Post-mortem vascular casting has been used to define the in vivo geometry for hemodynamic simulation; however, this procedure damages or destroys the tissue and cells on which biological assays are to be performed. METHOD OF APPROACH: Two statistical approaches, regional (RSH) and linear (LSH) statistical hemodynamics, are proposed and illustrated, in which flow simulations from one series of experiments are used to define a best estimate of the hemodynamic environment in a second series. As an illustration of the technique, RSH is used to compare the gene expression profiles of regions of the proximal external iliac arteries of swine exposed to different levels of time-average shear stress. RESULTS: The results indicate that higher shears promote a more atheroprotective expression phenotype in porcine arterial endothelium. CONCLUSION: Statistical hemodynamics provides a realistic estimate of the hemodynamic stress on vascular tissue that can be correlated against biological response.

Animals↗
PubMed1995

Modeling interstitial flow in an artery wall allows estimation of wall shear stress on smooth muscle cells.

The arterial media is modeled as a periodic array of cylindrical smooth muscle cells residing in a matrix comprised of proteoglycan and collagen fibers. Using Brinkman's model to describe transmural flow through such a fibrous media, we calculate the effective hydraulic permeability of the media and the wall shear stress on smooth muscle cells. Two interesting results are obtained: first, the wall shear stress on smooth muscle cells is on the order of 1 dyne/cm2, which is the range known to affect endothelial cells in vitro; second, the flow resistance due to smooth muscle cells is not negligible compared to the resistance due to the fiber matrix.

Arteries↗