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At least 505 records · Page 28Linked to original sources
PubMed1995

Why are some antiarrhythmic drugs proarrhythmic? Cardiac arrhythmia study by bifurcation analysis.

This study employs a bifurcation analysis approach to elucidate the effect of the key ion channels on cardiac arrhythmias and thereby explain the efficacy of antiarrhythmic drugs in controlling arrhythmias. The model used for the analysis contains the key ion channels involved in the ventricular action potential--fast sodium, slow calcium, and background potassium channels. The cardiac tissue is modeled by a ring structure. The bifurcation diagram reveals that at a certain ring size, the amplitude of the action potential suddenly shrinks and the conduction velocity (CV) becomes unstable. Instability in CV leads to termination of reentrant arrhythmias. This ring size (ie, the critical ring size [CRS]) depends of the type of channel blocker. Blocking of the sodium channel leads to a decrease in the CRS, which in turn enhances stable reentry (proarrhythmia). Although calcium channel blockers do not alter the CV, they can exert the proarrhythmic effect by drastically shortening the CRS. The potassium channel blockers, on the other hand, are effective in controlling reentry in ventricular tissues by lengthening the CRS. Near blocking of the potassium channel, however, brings about another type of arrhythmia--the formation of ectopic foci. In the neighborhood of the CRS, the cycle length oscillates with an interesting pattern that depends on ring size and drug type. Although a critical reentrant loop length for stable reentrant excitation has been investigated for a long time, this study is the first demonstration of how the key ion channels in the plasma membrane affect the loop length. Furthermore, the analysis approach provides a theoretical basis for the increased mortality associated with class I drug use in the Cardiac Arrhythmia Suppression Trial Team.

Action Potentials↗
PubMed1989

Physiological basis for mechanical time-variance in the heart: special consideration of non-linear function.

A relationship between ventricular pressure and volume is developed starting from basic cardiac muscle mechanics. The known and measurable properties of myocardium, such as the Hill law, the periodic excitation-contraction mechanism, and non-linear elasticity of the surrounding elastin and collagen structure, are formulated into a myofibril unit. A cylindrical geometry is chosen to represent the structure of the ventricle, using the myofibril unit as the basic building block. Pressure-volume isochrones computed from this model illustrate non-linear function in the heart which arises from both geometric effects and muscle effects. The above theory and model is linearized to provide a special study case. The behavior that resulted is that of a time-varying elastance, E(t), and, hence, can help in the interpretation of its meaning. It is found that the minimum in E(t) is the consequence of the stiffness of the myocardial fibrous network, adjusted by a geometric factor. In addition, the magnitude of E(t) is governed by myocardial contractility, a geometric factor, and the excitation-contraction mechanism, where time-dependency is imparted by periodic excitation. Since the elastic fibers are the only true elastic elements, the quantity of elastance is determined by controlled volume feedback. A circuit model is provided to illustrate this concept. The non-linear active and passive heart function curves are specified independently. These curves are required to intersect below the resting volume and result in a negative pressure at the intersection. This is found to explain the phenomenon of ventricular suction. In addition, they lead to a time-varying dead volume by virtue of time-dependent isochronal slope. Non-linear function is introduced to the model and is found to explain the variation in curvature of the ventricular isochrones.

Animals↗
PubMed2003

Left ventricular systolic performance in failing heart improved acutely by left ventricular reshaping.

OBJECTIVE: If the geometric distortion during dilated heart failure could be corrected, the tension on the myocytes would be decreased, thereby leading to an improvement in left ventricular systolic function. We tested the effects of the CardioClasp (CardioClasp Inc, Pine Brook, NJ), a left ventricular reshaping device, on the failing heart, and our empirical data were compared with computationally derived data. METHODS: Heart failure was induced by 4-week rapid cardiac pacing. At the terminal experiment, an isolated failing heart preparation (isovolumic contraction, n = 5) or an intact failing heart in vivo (n = 7) was used. The effects of the reshaping device on left ventricular performance were assessed by the slopes (Ees) of the left ventricular end-systolic pressure-volume relations, hemodynamics, and echocardiograph before and after placing the CardioClasp on the heart. The change in Ees as the result of left ventricular reshaping was also estimated from computed theoretical analysis and compared with empirical data. RESULTS: There was a significant change in left ventricular dimension after placing the CardioClasp on the heart. In isolated heart preparation, Ees significantly increased from 1.40 +/- 0.44 mm Hg/mL to 2.42 +/- 0.63 mm Hg/mL after placing the device on the heart but returned to the baseline level (1.46 +/- 0.27 mm Hg) after removing it. Left ventricular developed pressure and left ventricular fractional area shortening were significantly increased as the result of left ventricular reshaping. Ees derived from computed theoretical analysis was highly correlated with confirming empirical data. CONCLUSIONS: The CardioClasp can reshape the left ventricle and improve left ventricular systolic performance in failing hearts.

Animals↗
PubMed1996

Development of an intraluminal device for the treatment of aortic regurgitation: prototype and in vitro testing system.

OBJECTIVES: Development of an intraluminal device to reduce aortic regurgitation could provide a strategy intermediate between medical treatment and aortic valve replacement. An initial prototype and a testing system have been designed. METHODS: Aortic valves obtained from heart transplant recipients were explanted and assessed in a mock circulatory loop with resistive and capacitive elements, including pressure-flow characteristics, similar to those of a normal arterial system. Normal heart function was simulated by a pulsatile ventricular-assist device. Pressure on each side of the valve and flow through the valve were recorded, allowing the calculation of regurgitant fractions and transvalvular gradients. Six solid geometrically differing obturators were tested. RESULTS: All six designs resulted in significant reduction in aortic regurgitation (p < 0.0001), ranging from 15% to 38% improvement compared with control values. Small increases in transvalvular gradients (from 0 to 7 mm Hg) were also noted. DISCUSSION: Initial results suggest that an intraluminally placed obturator can reduce aortic regurgitation without creating clinically significant transvalvular gradients. These initial in vitro experiments demonstrate the feasibility of an intraluminal device for the treatment of aortic valve disease, and further investigation is warranted.

Aortic Valve↗
PubMed1998

Midterm results after aortic valve replacement with freehand stentless xenografts: a comparison of three prostheses.

OBJECTIVE: The ideal substitute for the diseased aortic valve is yet to be found. For the assessment and comparison of the midterm results after aortic valve replacement with three different types of freehand stentless xenografts, all patients who underwent the operation between October 1992 and April 1997 were reviewed. METHODS: Of 231 patients undergoing aortic valve replacement, 106 patients (group 1) were given the Biocor PSB (Biocor Industria e Pesquisa Ltda, Belo Horizonte, MG, Brazil); 76 patients (group 2) were given the Toronto SPV (St. Jude Medical, Inc., St. Paul, Minn.), and 49 patients (group 3) were given the O'Brien-Angell valve (Bravo Cardiovascular model 300, Cryolife, Inc., Marietta, Ga.). The first two xenografts require inflow and outflow suturelines; the third xenograft needs a single-sutureline implantation. Mean age (70 +/- 6 years; 70 +/- 7 years; 72 +/- 9 years; p = 0.6), prevalence of male sex (56 patients, 53%; 37 patients, 49%; 22 patients, 45%; p = 0.7), of aortic stenosis (72 patients, 68%; 54 patients, 71%; 37 patients, 73%; p = 0.6), and need for associated procedures (51 patients, 48%; 30 patients, 40%; 21 patients, 43%; p = 0.1) were comparable among groups. Mean aortic crossclamp time was shorter in group 3 (96 +/- 24 minutes; 100 +/- 23 minutes; 88 +/- 25 minutes;p = 0.01). RESULTS: Early deaths were 3 of 106 (3%) in group 1, 2 of 76 (3%) in group 2, and 2 of 49 (4%) in group 3. Follow-up of survivors ranged from 1 to 54 months (mean 32 +/- 13 months). Survival at 4 years was 90% +/- 3% in group 1, 95% +/- 3% in group 2, 85% +/- 8% in group 3 (p = 0.3). At 4 years, freedom from valve-related events was 95% +/- 6%, 100%, 70% +/- 8% (p = 0.004), while freedom from valve deterioration was 99% +/- 1%, 100%, 73% +/- 8% (p = 0.001), in group 1, 2, and 3, respectively (p = 0.001). At follow-up, reintervention on the xenograft was necessary in one patient (endocarditis) in group 1, none in group 2, and six in group 3 (technical cause, group 3; valve tear, group 2; pannus, group 1). Regression analysis showed O'Brien-Angell type of xenograft to be predictive of valve-related events (p = 0.02), valve deterioration (p = 0.001), and reoperation (p = 0.001) during follow-up. CONCLUSIONS: Midterm survival after stentless aortic valve replacement is good with all three xenografts. Freedom from valve-related events, valve deterioration, and reoperation are excellent with the Biocor PSB or the Toronto SPV stentless valves but less satisfactory with the O'Brien-Angell valve.

Aged↗
PubMedDate not supplied

Detecting autocatalytic dynamics in data modeled by a compartmental model.

Modeling growth or reaction dynamics within a compartment in a compartmental model is often based on theoretical or first principle considerations. This approach is frequently applied due to the inability to observe or collect data directly from the compartment. When the internal dynamics are difficult to surmise, it is often the case that several competing models are constructed and compared in some way. In this paper, the dynamics which characterize the data of an autocatalytic process are used to describe a quantitative data analysis strategy to both recognize the presence of the autocatalytic process and to obtain some estimates of important parameters in the process. The compartmental model structure serves to communicate this dynamical information to the downstream compartments. This method has been applied to examine the dynamics of the engraftment of blood cells following hematopoietic stem cell transplantation in a clinical setting [Modeling the time to engraftment of white blood cells and platelets following autologous peripheral blood stem cell transplantation (2001)].

Catalysis↗
PubMed1997

The inverse problem of electrocardiography: a solution in terms of single- and double-layer sources of the epicardial surface.

An approach to the inverse problem of electrocardiography that involves an estimation of the electric potentials (double-layer equivalent sources) on the heart's epicardial surface from the electrocardiographic potentials that are measurable on the body surface has received considerable attention. This report deals with a heretofore unexplored extension of this approach, one that yields, in addition to the electric potentials on the epicardial surface, the normal components of their gradients (single-layer equivalent sources). We show that this formulation has at least three advantages over the formulation in term of epicardial potentials alone: (1) single-layer equivalent sources, which reflect the flow of current across the epicardial surface, are well suited for the imaging of regional ischemia and infarction; (2) the transfer matrix linking the epicardial and body-surface potentials for this formulation is less ill conditioned than that for the formulation in terms of potentials alone; (3) the input vector for inverse calculations consists of spatially filtered (rather that directly measured and therefore noise) body-surface potentials. To establish the feasibility of this new formulation of the inverse problem and to compare it with the formulation in terms of potentials alone, we used a realistically shaped boundary-element model of human torso. By calculating singular values less ill conditioned. We then directly calculated epicardial and body-surface potentials for a single dipole located centrally and for three simultaneously active dipoles located eccentrically in the torso's heart region and used these results to test three methods that are prerequisites of a successful inverse solution: Tikhonov regularization, linearly constrained least squares, and an L-curve method. The feasibility of the new formulation was demonstrated by the fact that the method based on the linearly constrained least squares improved on overregularized Tikhonov solutions over a wide range of regularization parameters, and it yielded solutions that were more accurate than the best-possible Tikhonov solutions. Moreover, the L-curve solution procedure, which requires no a priori information about the solution, yielded slightly underregularized, but accurate, estimates for the optimal regularization parameter and the corresponding best-possible Tikhonov solution. Our results also showed that replacing--in the interest computational economy--quadrature formulas for the planar triangles with various approximate formulas for the nodes of the model reduces the accuracy of the inverse solution.

Electrocardiography↗
PubMedDate not supplied

Mechano-electric interactions in heterogeneous myocardium: development of fundamental experimental and theoretical models.

The heart is structurally and functionally a highly non-homogenous organ, yet its main function as a pump can only be achieved by the co-ordinated contraction of millions of ventricular cells. This apparent contradiction gives rise to the hypothesis that 'well-organised' inhomogeneity may be a pre-requisite for normal cardiac function. Here, we present a set of novel experimental and theoretical tools for the study of this concept. Heterogeneity, in its most condensed form, can be simulated using two individually controlled, mechanically interacting elements (duplex). We have developed and characterised three different types of duplexes: (i) biological duplex, consisting of two individually perfused biological samples (like thin papillary muscles or a trabeculae), (ii) virtual duplex, made-up of two interacting mathematical models of cardiac muscle, and (iii) hybrid duplex, containing a biological sample that interacts in real-time with a virtual muscle. In all three duplex types, in-series or in-parallel mechanical interaction of elements can be studied during externally isotonic, externally isometric, and auxotonic modes of contraction and relaxation. Duplex models, therefore, mimic (patho-)physiological mechano-electric interactions in heterogeneous myocardium at the multicellular level, and in an environment that allows one to control mechanical, electrical and pharmacological parameters. Results obtained using the duplex method show that: (i) contractile elements in heterogeneous myocardium are not 'independent' generators of tension/shortening, as their ino- and lusitropic characteristics change dynamically during mechanical interaction-potentially matching microscopic contractility to macroscopic demand, (ii) mechanical heterogeneity contributes differently to action potential duration (APD) changes, depending on whether mechanical coupling of elements is in-parallel or in-series, which may play a role in mechanical tuning of distant tissue regions, (iii) electro-mechanical activity of mechanically interacting contractile elements is affected by their activation sequence, which may optimise myocardial performance by smoothing intrinsic differences in APD. In conclusion, we present a novel set of tools for the experimental and theoretical investigation of cardiac mechano-electric interactions in healthy and/or diseased heterogeneous myocardium, which allows for the testing of previously inaccessible concepts.

Animals↗
PubMedDate not supplied

Sarcomere length changes in a 3D mathematical model of the pig ventricles.

Measurements of the geometry and fibrous-sheet structure of the left and right ventricles of the pig heart are fitted with a finite element model. Mechanical changes during the heart cycle are computed by solving the equations of motion under specified ventricular boundary conditions and using experimentally defined constitutive laws for the active and passive material properties of myocardial tissue. The resulting patterns of deformation, such as axial torsion and changes in wall thickness and base-apex length, are consistent with experimental observations. The model can therefore be used to predict sarcomere length changes and other strain patterns throughout the myocardium and throughout the cardiac cycle. Here we present sarcomere length changes at a limited number of material points within the wall. Sarcomere length typically varies by 10% above and below the unloaded length; although under the boundary conditions imposed in the current model the midwall circumferentially oriented sarcomere lengths increased by up to 20% at end diastole. We provide web-access details for a downloadable software program designed to provide more extensive information on mechanical deformation, such as the principal strains and muscle fibre cross-sectional area changes during the cardiac cycle.

Animals↗
PubMed1998

Adaptive local regularization methods for the inverse ECG problem.

One of the fundamental problems in theoretical electrocardiography can be characterized by an inverse problem. We present new methods for achieving better estimates of heart surface potential distributions in terms of torso potentials through an inverse procedure. First, we outline an automatic adaptive refinement algorithm that minimizes the spatial discretization error in the transfer matrix, increasing the accuracy of the inverse solution. Second, we introduce a new local regularization procedure, which works by partitioning the global transfer matrix into sub-matrices, allowing for varying amounts of smoothing. Each submatrix represents a region within the underlying geometric model in which regularization can be specifically 'tuned' using an a priori scheme based on the L-curve method. This local regularization method can provide a substantial increase in accuracy compared to global regularization schemes. Within this context of local regularization, we show that a generalized version of the singular value decomposition (GSVD) can further improve the accuracy of ECG inverse solutions compared to standard SVD and Tikhonov approaches. We conclude with specific examples of these techniques using geometric models of the human thorax derived from MRI data.

Algorithms↗
PubMed1992

Density of perfused capillaries in living human brain during functional activation.

Recent evidence has indicated that functional activation of cerebral cortex is accompanied by increases of blood flow and glucose consumption but not oxygen consumption. No explanation has been advanced for this change of the flow-metabolism couple. We formulated the hypothesis that oxygen delivery to brain tissue is diffusion-limited by the enormous hemoglobin binding, and rate-limiting for the oxygen consumption of the tissue. One prediction of this hypothesis is very low oxygen tensions in the tissue. A second prediction is the inability of oxygen consumption to increase during functional activation in the absence of recruitment of capillaries for the oxygen diffusion capacity. We designed a study to test the latter prediction by calculating the density of functioning capillaries during vibrotactile stimulation of the parietal cortex. We defined functioning capillaries as capillaries that transport glucose and therefore calculated the capillary density from the glucose diffusion capacity (K1) of the cerebral capillaries. We confirmed the presence of a partial flow-CMRglc couple (2:1) during the functional activation. Oxygen consumption did not change despite an increase of capillary density in proportion to the change of blood flow.

Brain↗
PubMed2000

Movement of zinc and its functional significance in the brain.

Zinc, an essential nutrient, is supplied to the brain via both the blood-brain and blood-cerebrospinal fluid barriers. Zinc is most concentrated in the limbic system, i.e. the hippocampus and amygdala, zinc-containing glutaminergic neuron-rich areas. A large portion of zinc serves the function of zinc metalloproteins in neurons and glial cells. In zinc-containing glutaminergic neurons, vesicular zinc, probably ionic zinc, may serve as an endogenous neuromodulator in synaptic neurotransmission. Vesicular zinc is dynamically coupled to the electrophysiological activity of zinc-containing glutaminergic neurons. Dietary zinc deprivation may influence zinc homeostasis in the brain, resulting in brain dysfunction such as learning impairment. Excessive excitation of zinc-containing glutaminergic neurons causes a decrease in vesicular zinc, and the decrease might be associated with the susceptibility to seizure. Alteration of zinc levels released into the synaptic cleft may influence neurotransmission in zinc-containing glutaminergic synapses. Therefore, zinc homeostasis in the presynaptic vesicle is important for the function of zinc-containing glutaminergic neurons.

Animals↗
PubMed2001

Quantitative assessment of in vitro jets based on three-dimensional color Doppler reconstruction.

Three-dimensional (3-D) color Doppler imaging of flow jets was performed to investigate the effects of flow rate and orifice size on jet volumes. Flow jets were generated using a flow model to simulate mitral regurgitation. This flow model consisted of a ventricular chamber, a valvular plate and an atrial chamber. Steady flow was driven through circular orifices having diameters of 2.5, 3.5, 4.5, and 6 mm, respectively, with flow rates of 5, 10, 15, 20, and 25 mL/s to form free jets in the atrial chamber. An ATL Ultramark 9 HDI system was used to perform 3-D color Doppler imaging of the flow jets. A transesophageal probe was rotated by a stepper motor to create 3-D color Doppler images of the jets. The color jet volumes for different hemodynamic conditions were measured and then compared with the theoretical predictions. Results showed that the jet volume estimated from the 3-D color Doppler was directly proportional to the flow rate and inversely proportional to the orifice size. The estimated jet volumes correlated well (r > 0.95) with theoretical predictions. This study supports the use of color jet volume as a parameter to quantify mitral regurgitation.

Blood Flow Velocity↗
PubMed2001

Performance of time-frequency representation techniques to measure blood flow turbulence with pulsed-wave Doppler ultrasound.

The current processing performed by commercial instruments to obtain the time-frequency representation (TFR) of pulsed-wave Doppler signals may not be adequate to characterize turbulent flow motions. The assessment of the intensity of turbulence is of high clinical importance and measuring high-frequency (small-scale) flow motions, using Doppler ultrasound (US), is a difficult problem that has been studied very little. The objective was to optimize the performance of the spectrogram (SPEC), autoregressive modeling (AR), Choi-Williams distribution (CWD), Choi-Williams reduced interference distribution (CW-RID), Bessel distribution (BD), and matching pursuit method (MP) for mean velocity waveform estimation and turbulence detection. The intensity of turbulence was measured from the fluctuations of the Doppler mean velocity obtained from a simulation model under pulsatile flow. The Kolmogorov spectrum, which is used to determine the frequency of the fluctuations and, thus, the scale of the turbulent motions, was also computed for each method. The best set of parameters for each TFR method was determined by minimizing the error of the absolute frequency fluctuations and Kolmogorov spectral bandwidth measured from the simulated and computed Doppler spectra. The results showed that different parameters must be used for each method to minimize the velocity variance of the estimator, to optimize the detection of the turbulent frequency fluctuations, and to estimate the Kolmogorov spectrum. To minimize the variance and to measure the absolute turbulent frequency fluctuations, four methods provided similar results: SPEC (10-ms sine-cosine windows), AR (10-ms rectangular windows, model order = 8), CWD (w(N) and w(M) = 10-ms rectangular windows, sigma = 0.01), and BD (w(N) = 10-ms rectangular windows, alpha = 16). The velocity variance in the absence of turbulence was on the order of 0.04 m/s (coefficient of variation ranging from 8.0% to 14.5%, depending on the method). With these spectral techniques, the peak of the turbulence intensity was adequately estimated (velocity bias < 0.01 m/s). To track the frequency of turbulence, the best method was BD (w(N) = 2-ms rectangular windows, alpha = 2). The bias in the estimate of the -10 dB bandwidth of the Kolmogorov spectrum was 354 +/- 51 Hz in the absence of turbulence (the true bandwidth should be 0 Hz), and -193 +/- 371 Hz with turbulence (the simulated -10-dB bandwidth was estimated at 1256 Hz instead of 1449 Hz). In conclusion, several TFR methods can be used to measure the magnitude of the turbulent fluctuations. To track eddies ranging from large vortex to small turbulent fluctuations (wide Kolmogorov spectrum), the Bessel distribution with appropriate set of parameters is recommended.

Blood Flow Velocity↗
PubMed1998

Validation of a new blood-mimicking fluid for use in Doppler flow test objects.

A blood-mimicking fluid (BMF) suitable for use in Doppler flow test objects is described and characterised. The BMF consists of 5 microns diameter nylon scattering particles suspended in a fluid base of water, glycerol, dextran and surfactant. The acoustical properties of various BMF preparations were measured under uniform flow to study the effects of particle size, particle concentration, surfactant concentration, flow rate and stability. The physical properties, (density, viscosity and particle size), and acoustical properties (velocity, backscatter and attenuation) of the BMF are within draft International Electrotechnical Commission requirements.

Blood Flow Velocity↗
PubMed2002

Real-time computer simulations of excitable media: JAVA as a scientific language and as a wrapper for C and FORTRAN programs.

We describe a useful setting for interactive, real-time study of mathematical models of cardiac electrical activity, using implicit and explicit integration schemes implemented in JAVA. These programs are intended as a teaching aid for the study and understanding of general excitable media. Particularly for cardiac cell models and the ionic currents underlying their basic electrical dynamics. Within the programs, excitable media properties such as thresholds and refractoriness and their dependence on parameter values can be analyzed. In addition, the cardiac model applets allow the study of reentrant tachyarrhythmias using premature stimuli and conduction blocks to induce or to terminate reentrant waves of electrical activation in one and two dimensions. The role of some physiological parameters in the transition from tachycardia to fibrillation also can be analyzed by varying the maximum conductances of ion channels associated with a given model in real time during the simulations. These applets are available for download at http://arrhythmia.hofstra.edu or its mirror site http://stardec.ascc.neu.edu/~fenton.

Algorithms↗