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At least 1,117 records · Page 62Linked to original sources
PubMed2002

Comparison of regularization techniques for the reconstruction of transmembrane potentials in the heart.

Computer simulations to reconstruct the transmembrane potential distribution were performed for an anisotropic finite element model of the heart. Transmembrane potential was reconstructed in the form of 3D patches. Test patterns generated with a cellular automaton were used. Tikhonov 0-order and 2-order reconstruction techniques were compared. Tikhonov 2-order regularization was shown to deliver better solutions; this is demonstrated by the inspection of the source space of the inverse problem and by the comparison of the correlation coefficients between the reconstructed and original distributions. Time information was incorporated into the regularization.

Body Surface Potential Mapping↗
PubMed2002

[Multi-value regulatory systems for extracorporeal circulation].

Extracorporeal perfusion is the standard technique in cardiac surgery. It is controlled by perfusionists on the basis of their clinical experience and on the available data collected pre- and intra-operatively. But in spite of intensive monitoring postoperative complications occur. An appropriate control of the heart-lung machine (HLM) using an "autopilot" might improve the quality of heart-surgery and decrease postoperative complications. Hence, a mathematical model of a human circulatory system has been developed which provides much more information about haemodynamics, blood gases and acid-base status than standard monitoring. It has been implemented on a system which is capable of integrating measured data as input parameters in real-time in the simulation. Now, soft- and hardware control concepts based on the human circulatory system have to be developed which are able to control the HLM.

Coronary Disease↗
PubMed2004

Using a hybrid neural system to reveal regulation of neuronal network activity by an intrinsic current.

The generation of rhythmic patterns by neuronal networks is a complex phenomenon, relying on the interaction of numerous intrinsic and synaptic currents, as well as modulatory agents. To investigate the functional contribution of an individual ionic current to rhythmic pattern generation in a network, we constructed a hybrid system composed of a silicon model neuron and a heart interneuron from the heartbeat timing network of the medicinal leech. When the model neuron and a heart interneuron are connected by inhibitory synapses, they produce rhythmic activity similar to that observed in the heartbeat network. We focused our studies on investigating the functional role of the hyperpolarization-activated inward current (I(h)) on the rhythmic bursts produced by the network. By introducing changes in both the model and the heart interneuron, we showed that I(h) determines both the period of rhythmic bursts and the balance of activity between the two sides of the network, because the amount and the activation/deactivation time constant of I(h) determines the length of time that a neuron spends in the inhibited phase of its burst cycle. Moreover, we demonstrated that the model neuron is an effective replacement for a heart interneuron and that changes made in the model can accurately mimic similar changes made in the living system. Finally, we used a previously developed mathematical model (Hill et al. 2001) of two mutually inhibitory interneurons to corroborate these findings. Our results demonstrated that this hybrid system technique is advantageous for investigating neuronal properties that are inaccessible with traditional techniques.

Analysis of Variance↗
PubMed2004

Multiphysics simulation of left ventricular filling dynamics using fluid-structure interaction finite element method.

To relate the subcellular molecular events to organ level physiology in heart, we have developed a three-dimensional finite-element-based simulation program incorporating the cellular mechanisms of excitation-contraction coupling and its propagation, and simulated the fluid-structure interaction involved in the contraction and relaxation of the human left ventricle. The FitzHugh-Nagumo model and four-state model representing the cross-bridge kinetics were adopted for cellular model. Both ventricular wall and blood in the cavity were modeled by finite element mesh. An arbitrary Lagrangian Eulerian finite element method with automatic mesh updating has been formulated for large domain changes, and a strong coupling strategy has been taken. Using electrical analog of pulmonary circulation and left atrium as a preload and the windkessel model as an afterload, dynamics of ventricular filling as well as ejection was simulated. We successfully reproduced the biphasic filling flow consisting of early rapid filling and atrial contraction similar to that reported in clinical observation. Furthermore, fluid-structure analysis enabled us to analyze the wave propagation velocity of filling flow. This simulator can be a powerful tool for establishing a link between molecular abnormality and the clinical disorder at the macroscopic level.

Biophysical Phenomena↗
PubMed2004

Asymmetry in membrane responses to electric shocks: insights from bidomain simulations.

Models of myocardial membrane dynamics have not been able to reproduce the experimentally observed negative bias in the asymmetry of transmembrane potential changes (DeltaVm) induced by strong electric shocks delivered during the action potential plateau. The goal of this study is to determine what membrane model modifications can bridge this gap between simulation and experiment. We conducted simulations of shocks in bidomain fibers and sheets with membrane dynamics represented by the LRd'2000 model. We found that in the fiber, the negative bias in DeltaVm asymmetry could not be reproduced by addition of electroporation only, but by further addition of hypothetical outward current, Ia, activated upon strong shock-induced depolarization. Furthermore, the experimentally observed rectangularly shaped positive DeltaVm, negative-to-positive DeltaVm ratio (asymmetry ratio) = approximately 2, electroporation occurring at the anode only, and the increase in positive DeltaVm caused by L-type Ca2+-channel blockade were reproduced in the strand only if Ia was assumed to be a part of K+ flow through the L-type Ca2+-channel. In the sheet, Ia not only contributed to the negative bias in DeltaVm asymmetry at sites polarized by physical and virtual electrodes, but also restricted positive DeltaVm. Inclusion of Ia and electroporation is thus the bridge between experiment and simulation.

Action Potentials↗
PubMed2005

Experimental generation and computational modeling of intracellular pH gradients in cardiac myocytes.

It is often assumed that pH(i) is spatially uniform within cells. A double-barreled microperfusion system was used to apply solutions of weak acid (acetic acid, CO(2)) or base (ammonia) to localized regions of an isolated ventricular myocyte (guinea pig). A stable, longitudinal pH(i) gradient (up to 1 pH(i) unit) was observed (using confocal imaging of SNARF-1 fluorescence). Changing the fractional exposure of the cell to weak acid/base altered the gradient, as did changing the concentration and type of weak acid/base applied. A diffusion-reaction computational model accurately simulated this behavior of pH(i). The model assumes that H(i)(+) movement occurs via diffusive shuttling on mobile buffers, with little free H(+) diffusion. The average diffusion constant for mobile buffer was estimated as 33 x 10(-7) cm(2)/s, consistent with an apparent H(i)(+) diffusion coefficient, D(H)(app), of 14.4 x 10(-7) cm(2)/s (at pH(i) 7.07), a value two orders of magnitude lower than for H(+) ions in water but similar to that estimated recently from local acid injection via a cell-attached glass micropipette. We conclude that, because H(i)(+) mobility is so low, an extracellular concentration gradient of permeant weak acid readily induces pH(i) nonuniformity. Similar concentration gradients for weak acid (e.g., CO(2)) occur across border zones during regional myocardial ischemia, raising the possibility of steep pH(i) gradients within the heart under some pathophysiological conditions.

Acetates↗
PubMed2005

Dynamical mechanisms of pacemaker generation in IK1-downregulated human ventricular myocytes: insights from bifurcation analyses of a mathematical model.

Dynamical mechanisms of the biological pacemaker (BP) generation in human ventricular myocytes were investigated by bifurcation analyses of a mathematical model. Equilibrium points (EPs), periodic orbits, stability of EPs, and bifurcation points were determined as functions of bifurcation parameters, such as the maximum conductance of inward-rectifier K+ current (I(K1)), for constructing bifurcation diagrams. Stable limit cycles (BP activity) abruptly appeared around an unstable EP via a saddle-node bifurcation when I(K1) was suppressed by 84.6%. After the bifurcation at which a stable EP disappears, the I(K1)-reduced system has an unstable EP only, which is essentially important for stable pacemaking. To elucidate how individual sarcolemmal currents contribute to EP instability and BP generation, we further explored the bifurcation structures of the system during changes in L-type Ca2+ channel current (I(Ca,L)), delayed-rectifier K+ currents (I(K)), or Na(+)/Ca2+ exchanger current (I(NaCa)). Our results suggest that 1), I(Ca,L) is, but I(K) or I(NaCa) is not, responsible for EP instability as a requisite to stable BP generation; 2), I(K) is indispensable for robust pacemaking with large amplitude, high upstroke velocity, and stable frequency; and 3), I(NaCa) is the dominant pacemaker current but is not necessarily required for the generation of spontaneous oscillations.

Biological Clocks↗
PubMed2005

Genesis of ectopic waves: role of coupling, automaticity, and heterogeneity.

Many arrhythmias are believed to be triggered by ectopic sources arising from the border of the ischemic tissue. However, the development of ectopic activity from individual sources to a larger mass of cardiac tissue remains poorly understood. To address this critical issue, we used monolayers of neonatal rat cardiomyocytes to create conditions that promoted progression of ectopic activity from single cells to the network that consisted of hundreds of cells. To explain complex spatiotemporal patterns observed in these experiments we introduced a new theoretical framework. The framework's main feature is a parameter space diagram, which uses cell automaticity and coupling as two coordinates. The diagram allows one to depict network behavior, quantitatively address the heterogeneity factor, and evaluate transitions between different regimes. The well-organized wave trains were observed at moderate and high cell coupling values and network heterogeneity was found to be qualitatively unimportant for these regimes. In contrast, at lower values of coupling, spontaneous ectopic activity led to the appearance of fragmented ectopic waves. For these regimes, network heterogeneity played an essential role. The ectopic waves occasionally gave rise to spiral activity in two different regions within the parameter space via two distinct mechanisms. Together, our results suggest that localized ectopic waves represent an essential step in the progression of ectopic activity. These studies add to the understanding of initiation and progression of arrhythmias and can be applied to other phenomena that deal with assemblies of coupled oscillators.

Action Potentials↗
PubMed2006

Calcium instabilities in mammalian cardiomyocyte networks.

The degeneration of a regular heart rhythm into fibrillation (a chaotic or chaos-like sequence) can proceed via several classical routes described by nonlinear dynamics: period-doubling, quasiperiodicity, or intermittency. In this study, we experimentally examine one aspect of cardiac excitation dynamics, the long-term evolution of intracellular calcium signals in cultured cardiomyocyte networks subjected to increasingly faster pacing rates via field stimulation. In this spatially extended system, we observed alternans and higher-order periodicities, extra beats, and skipped beats or blocks. Calcium instabilities evolved nonmonotonically with the prevalence of phase-locking or Wenckebach rhythm, low-frequency magnitude modulations (signature of quasiperiodicity), and switches between patterns with occasional bursts (signature of intermittency), but period-doubling bifurcations were rare. Six ventricular-fibrillation-resembling episodes were pace-induced, for which significantly higher complexity was confirmed by approximate entropy calculations. The progressive destabilization of the heart rhythm by coexistent frequencies, seen in this study, can be related to theoretically predicted competition of control variables (voltage and calcium) at the single-cell level, or to competition of excitation and recovery at the cell network level. Optical maps of the response revealed multiple local spatiotemporal patterns, and the emergence of longer-period global rhythms as a result of wavebreak-induced reentries.

Action Potentials↗
PubMed2006

Conditions for propagation and block of excitation in an asymptotic model of atrial tissue.

Detailed ionic models of cardiac cells are difficult for numerical simulations because they consist of a large number of equations and contain small parameters. The presence of small parameters, however, may be used for asymptotic reduction of the models. Earlier results have shown that the asymptotics of cardiac equations are nonstandard. Here we apply such a novel asymptotic method to an ionic model of human atrial tissue to obtain a reduced but accurate model for the description of excitation fronts. Numerical simulations of spiral waves in atrial tissue show that wave fronts of propagating action potentials break up and self-terminate. Our model, in particular, yields a simple analytical criterion of propagation block, which is similar in purpose but completely different in nature to the "Maxwell rule" in the FitzHugh-Nagumo type models. Our new criterion agrees with direct numerical simulations of breakup of reentrant waves.

Action Potentials↗
PubMed1989

Radionuclide left ventricular absolute volume determination by ejection fraction measurement data and a left posterior oblique blood pool image.

A new method for the calculation of left ventricular volumes called the "semi-geometric" method, was reported by Nichols et al in 1984. This method, however, still had certain limitations for practical use. This paper describes a modified semi-geometric method in which the left ventricular volume was obtained from conventional left ventricular ejection fraction measurement data collected from the modified left anterior oblique position with a caudal tilt of 10 degrees or more and a left posterior oblique blood pool image. The left ventricular end-diastolic volumes obtained by this method were compared with those calculated by combining the thermodilution cardiac output and the left ventricular ejection fraction. The correlation coefficient was r = 0.93 (n = 20). In the phantom experiment, the true volumes and those obtained by this method showed an excellent correlation (r = 0.99). This method is considered accurate and practical.

Adult↗
PubMed1993

Ca2+ sensitivity of contractile machinery and Ca2+ handling energy. Simulation.

Myocardial Ca2+ handling during excitation-contraction coupling has been modelled mathematically to gain a better insight into the expectation that Ca2+ sensitization of contractile machinery may save myocardial energy utilization for Ca2+ handling. The basic model of myocardial Ca2+ kinetics and mechanoenergetics involved the sarcoplasmic reticulum (SR), sarcoplasm, troponin C (Tn) and crossbridges (CB). The relations among the released Ca2+ ions from the SR, peak concentrations of sarcoplasmic free Ca2+ ([Ca2+]i) and Ca(2+)-bound troponin ([TnCa]) and peak contractile force were computed, based upon the assumptions that the released Ca2+ ions diffuse as free Ca2+ in sarcoplasm, bind kinetically with Tn with an association rate constant of k1, dissociate from TnCa with a dissociation rate constant of k2, and are sequestered into the SR with consumption of ATP. TnCa was associated with CB cycling to develop force with a set of given on and off rate constants. The association constant Ka (= k1/k2) of TnCa as an index of Ca2+ sensitivity of Tn was varied 32-fold from 0.25 to 8/microM. Results showed that Ca2+ sensitization from a lower Ka level could most sharply decrease the total Ca2+ release required to develop the same contractile force. Thus, it would reduce the total Ca2+ handling energy that the SR uses to maintain the same contractility.

Calcium↗
PubMed1994

Possible clinical applications of the external work reserve of the myocardium.

The concept of external work reserve (EWR) related to the end-systolic pressure-volume relation in the left ventricle and introduced in previous publications is investigated. The potential clinical usefulness of indexes related to EWR as well as to different areas under the end-systolic pressure volume line (ESPVL) is indicated. The possibility of non-invasive clinical application of the results of this study is discussed.

Energy Metabolism↗
PubMed1996

The mechanism of the physiologic disappearance of the third heart sound with aging.

The third heart sound (S3) is often present in children and adolescents but is not present in most adults. Applying at the left ventricle a mathematical model, the mechanism of the disappearance of S3 was studied employing the frequency analysis of the sound and echocardiographic data. The existence of a significant correlation between the spectrum energy of S3 and the diameter and thickness of the left ventricle at the moment of S3 in 25 healthy subjects (aged 21 +/- 7 years) allowed us to interpret the origin of S3 based on a viscoelastic oscillating system. Once the left ventricle starts vibrating it behaves as a simple physical model composed of a mass (m), a spring (k) and a viscous element. The abrupt deceleration of the blood mass (m) against the left ventricular walls (k) triggers the vibration of the system according to the equation Fd = 1/2 pi.square root of k/m.square root of 1 - zeta 2, where Fd is the natural damped frequency and zeta is the damping factor. The equation shows that the vibrating system can oscillate only if zeta is < 1. During the growth of the individual the increased myocardial mass may lead to augmented viscous forces causing a gradual increase in zeta until the system becomes overdamped and consequently unable to vibrate causing the disappearance of S3.

Adult↗
PubMed2004

Residual stenosis poststenting and subsequent decrease in the proximal reference diameter are correlated: excessive axial wall stress is a plausible explanation.

PURPOSE: To test the hypothesis that edge restenosis in stented lesions might be due to an increase in axial wall stress in the adjacent proximal vessel segment by examining whether the proximal reference diameters of conventionally stented lesions are reduced at follow-up and whether this reduction depends on the degree of residual stenosis poststenting. METHODS: The literature published in the past 5 years dealing with restenosis following implantation of standard stents was screened for the availability of (1) reference vessel diameters poststenting, (2) mean residual stenosis poststenting, and (3) mean reference vessel diameters at follow-up in the same patients or groups of patients. Data collected from 11 publications were pooled and used to compute the change in reference segment diameter over time. These differences were compared to the residual stenosis poststenting by nonlinear regression. RESULTS: The reduction in the mean reference diameters over time and the mean residual stenosis poststenting appear to be strongly correlated (r2 = 0.838), which supports the idea that the evolution of a stenosis adjacent to a stent margin depends on the severity of the residual stenosis. CONCLUSIONS: This finding indicates that edge restenosis might be due to excessive axial wall stress. It may also explain, at least partly, why edge restenosis is observed with catheter-based brachytherapy and radioactive or drug-eluting stents.

Arterial Occlusive Diseases↗
PubMed2005

Mathematical models of oxygen and carbon dioxide storage and transport: the acid-base chemistry of blood.

This article describes a mathematical model of the acid-base chemistry of blood. The model is formulated from first principles by considering the "components" of blood and the reaction equations in the plasma and erythrocyte fractions. Equations are formulated to describe the total concentration of blood components, the physicochemical properties, and the equilibrium position of reactions. The model includes 28 equations and 12 parameters. All equations can be solved from six variables included in the model. The model uses simple mathematics, without introducing intermediate concepts or linear coefficients necessary for algebraic solution. Model equations are solved simultaneously using numerical methods. Model parameters are estimated and the model verified for plasma, fully oxygenated blood, and deoxygenated blood. Published data are used to estimate model parameters and normal conditions and to verify model simulations. The model reproduces experimental results, including addition or removal of CO2, or strong acid to plasma; CO2, strong acid or haemoglobin to blood; and the effects of deoxygenating blood. The model can also be used as the basis for models of whole body CO2 transport as illustrated in the accompanying article. As such, it is possible to simulate the effects on blood of physiological changes in ventilation or metabolism.

Acid-Base Equilibrium↗
PubMed2003

Artificial cerebral aneurysm model for medical testing, training, and research.

Artificial models of cerebral aneurysms for medical training and testing of medical devices were constructed from corrosion casts of the main cerebral arteries of a human specimen. Three aneurysms with a variety of shapes were simulated at typical locations. Rigid and soft models were made of silicone using the "lost wax" technique. The transparent silicone models were anatomically accurate and reproducible copies of human vascular casts. These models could be connected in a closed circuit that used an electric pump to simulate pulsatile flow. Endovascular procedures and surgical clip application were performed under fluoroscopic or direct visual control. Surgical clipping, endoluminal coil manipulation, and consecutive hemodynamic changes were visualized by digital subtraction angiography and direct observation. The model provides trainee surgeons with an understanding of clinical conditions. New medical devices, such as platinum coils, would be experimentally implanted in the model under stable conditions. These anatomically accurate and reproducible models of cerebral vasculature and aneurysms are valuable for medical testing, training, and research.

Corrosion Casting↗
PubMed1991

Right and left ventricular stroke volume measurements with velocity-encoded cine MR imaging: in vitro and in vivo validation.

The accuracy of measurements of flow velocity determined by using cine MR phase velocity mapping--velocity-encoded cine (VEC) MR--was assessed by comparing VEC MR data with independent measurements in a flow phantom and in human subjects. Constant flow velocities generated in a phantom (range, 20-408 cm/sec) were determined correctly by VEC MR (r = .997, standard error of the estimate [SEE] = 7.9 cm/sec). Peak systolic velocities in the main pulmonary artery determined by VEC MR correlated well with the measurements obtained by using continuous-wave Doppler echocardiography (r = .91). Stroke volumes measured at the aorta by VEC MR and continuous-wave Doppler imaging also correlated well with each other (r = .80). VEC MR measurements of aortic and pulmonary flow provided left and right ventricular stroke volumes that correlated well with left ventricular stroke volumes determined by short-axis cine MR images (r = .98, SEE = 3.7 ml, and r = .95, SEE = 4.8 ml, respectively). Intra- and interobserver variabilities were small for both left and right ventricular stroke volumes as measured with VEC MR. These results indicate that VEC MR accurately and reproducibly measures aortic and pulmonary flow velocities and volumes in the physiologic range of humans, and can be used to measure right and left ventricular stroke volumes under normal flow conditions.

Adult↗