R-3 Repository :: Browsing by Author "Clark, John W."

Browsing by Author "Clark, John W."

Now showing 1 - 19 of 19

A mathematical model of the vagally driven primary pacemaker cell membrane of the SA node of the heart
(1982) Bristow, David Graham; Clark, John W.; Glantz, Raymon M.; Johnson, Don H.
The study of the electrophyslologlcal activity of the SA node of the heart is currently a subject of considerable Interest In the research community. Information regarding the electrical behavior of the SA node Is by no means complete, yet sufficiently detailed Information Is available In the literature to allow the formulation of a reasonably quantitative model of the primary pacemaker cell membrane, and its vagal Innervation. In this study, the well-known McAlIIster-Noble-Tslen model of cardiac Purklnje fiber Is modified to account for the electrical activity of the SA node. To model the effects of vagal activity on the sinus rhythm a muscarinic channel with dynamics as suggested by Purves and Noma et al. has been added to the basic membrane model. The model mimics the published data quite well and Is capable of characterizing the free running behavior of the SA node, as well as Its response to electrotonic and vagal stimulation.
A mathematical reconstruction of the frog atrial action potential based on voltage clamp data
(1983) Robinson, Keith; Clark, John W.; Glantz, Raymon M.; Johnson, Don H.
Recent advances in cardiac electrophysiology have allowed for the preparation of viable single frog atrial cells. These cells have properties which make them ideal for voltage clamp studies. The ionic currents observed under voltage clamp conditons from single frog atrial cells are analyzed with the use of automatic methods programmed on a computer. From the analyzed data, mathematical models are formed which describe the time and voltage dependence of the various ionic currents observed under voltage clamp conditions. These models are then combined, and a membrane action potential is reconstructed based on the analyzed ionic current data. This membrane action potential is then used as input to a nonlinear least-squares fitting routine in an attempt to accurately fit the model to experimental action potential data.
A nonlinear adaptive equalizer
(1980) Wendt, Richard Ernest; Figueiredo, Rui J. P. de; Clark, John W.; Johnson, Don H.
The problem of removal of distortion caused by nonlinearities is investigated in light of a known technique of equalization. This inline, open loop, procedure, involving a contraction mapping, is well suited to compensating systems whose inputs are inaccessible. The present contribution is to add an adaptive capability to the scheme, extending its applicability to systems whose nonlinear parameters are unknown or drifting. Results of computer simulations are presented.
A study of the phase sensitivity between pacemaker response and vagal stimulation
(1974) Greco, Edward Carl; Clark, John W.
This study investigates the importance of the phase relation between vagal activity and the resulting chronotropic effect on the heart’s pacemaker. Both the transient nature of the pacemaker response to a single vagal burst of activity, preceded and followed by silence, and the steady-state pacemaker response to a continuous periodic vagal activity are examined. The response to transient vagal activity has two salient characteristics; 1) vagal activity which occurs sufficiently late in a pacemaker period will have no effect on that period; however, the following periods will be altered. 2) the first period in which the stimulus occurs will be either increased or remain unchanged (as stated in 1); the second and third periods may be decreased below the control period, depending upon the phase relation between vagal and pacemaker activity and the intensity of the vagal activity; the fourth, fifth, and etc. periods are greater than the control period and decay exponentially to the control period as the time from stimulus increases. This information is presented in the form of the Inhibition Curve. The pacemaker response to vagal activity becomes locked (entrained) to the steady-state vagal activity at the fundamental, ie, one occurrence of vagal activity during each pacemaker period, and at higher and subharmonics of the vagal activity rate. This entrainment phenomena was evident in the constant phase relation between the pacemaker and vagal activity. During entrainment an increase in the rate of vagal activity would cause a paradoxical increase in the pacemaker rate; however, over the entire spectrum of vagal activity rate, the trend was the expected decrease in pacemaker rate with increased vagal activity rate. A mathematical model has been developed to mimic pacemaker response to vagal activity. The model is composed of a relaxation oscillator with an unforced rate corresponding to the denervated pacemaker rate. The neuro-chemical transmitter and its effect on the pacemaker is modeled with a linear filter and nonlinear gain. The vagal stimulus is represented by an impulse in the model. Data has been obtained from the dog where vagal activity was initiated by supramaximal burst stimulation of the vagus nerve (1 msec pulses with 11 msec intraburst period) of 1,3 or 5 pulses/burst. Propranolol was administered (1 mg/kg) to block all sympathetic activity, and atrial activity, via a bipolar electrode in the atrium, was used as an indication of the pacemaker activation. The model parameters were chosen such that the model responded to transient activation as did the data. The model was then shown to exhibit entrainment to continuous periodic input as does the data.
A two-stage identification scheme for the determination of the parameters of a lumped parameter model of the left heart and systemic circulation
(1975) Ling, Robert Y. B.; Clark, John W.
In this study, a clinically-oriented, lumped parameter model of the human systemic circulatory system and the left ventricle is presented and identification of the model parameters is achieved by using a two-stage parameter estimation scheme that utilizes averaged pressure data (obtained from a single solid-state transducer) at three anatomical sites (proximal brachial artery, ascending aorta and left ventricle). The model parameters obtained using the estimation scheme are reasonable in a physical sense and provide a good fit to aortic and brachial pressures. The flow waveform at the aortic root can be computed during the systolic portion of the cycle, and from this waveform, instantaneous left ventricular volume (LW) changes can be predicted. As a check on the method, instantaneous LW is measured on the same patient via single plane cineangiography and compared with model generaged curves that employ the measured cineangiographic value of end-diastolic volume. In addition, the modulus and phase angle of the ascending aorta impedance, computed from the parameter values of the model, compare favorably with those obtained from more complex simulations as well as with clinical measurements. The method is simple, utilizes only pressure data (which is usually recorded with very little measurement error), and uses measurement techniques that are currently routinely employed in cardiac catheterization laboratories. The identification scheme provides an estimate of lumped proximal and distal arterial load parameters, aortic valve resistance, ascending aortic flow, ventricular volume changes, stroke volume and ejection fraction, for an individual patient.
An elastance characterization of the normal and failing heart
(1974) Baldridge, David Lawrence; Clark, John W.
The contractile state of the left ventricle of the heart is shown to be uniquely characterized by the ventricle's instantaneous pressure-volume ratio or elastance (Ev(t)). This unique characterization enables various disease states to be distinguished by respective parameters derived from the elastance function, the respective parameters being used to form indices of the myocardial contractile state (myocardial contractility). Previous methods of characterizing the contractile state of the left ventricle (which utilize a microscopic view of individual cardiac muscle fibers) are examined and their strengths and weaknesses are presented. The relation ship of these methods to the elastance characterization (which utilizes a macroscopic view of muscle) is shown and the advantages of the Ev(t) method are given. Although an historically controversial topic, the dependence of elastance on the preload (end-diastolic volume, Ve(j) of the heart is first shown to exist in the normal dog. This dependence is expressed in terms of the relationship of Ve(j to peak elastance and time to Ev,max from start of systole. After fitting human elastance data with a new and improved elastance curvefitting method utilizing spline functions, the same relationship to Vecj as in the dog is shown to exist in man, both for the normal and the failing heart. In addition to the normal heart, the disease states studied include asynergism (the state of partial wall akinesis or dyskinesis during contraction) and coronary artery disease (CAD). Characteristic elastance functions (dependent on Ved) are shown to exist for the normal, asynergic, and CAD hearts, with the CAD hearts demonstrating two distinct elastance functions, one being associated with a more advanced deterioration of the myocardial contractile state than the other. Using these 'characteristic elastance functions, various parameters derived from the elastance functions are shown to distinguish the normal contractile state from that of the asynergic and CAD patients, the CAD patients existing at a lower state of myocardial contractility than the normal patients but at a higher state than the asynergic patients. Being a preliminary study, areas of extension and additional applications of the elastance characterization of disease states are presented.
An electrophysiologic investigation of the normal and ischemic left ventricle
(1974) Wells, Darrel Richard; Clark, John W.
An electrophysiologic investigation of the normal and ischemic left ventricle is conducted using the chronic conscious pig as the experimental model. The experimental conditions imposed upon this preparation include mechanical occlusion of the left anterior descending coronary artery, cerebral stimulation and administration of an anti-arrhythmic drug, propranolol. The occlusion experiments are primarily of a temporary nature in order to study the early effects of acute myocardial ischemia; long term occlusion experiments are also conducted in order to investigate the transition from severe ischemia to myocardial infarction. The central nervous system is postulated to exert a major influence in the electrogenesis of cardiac arrhythmias and ventricular fibrillation in the ischemic heart. Psychological adaptation of the conscious animal to the experimental environment appears to prevent ventricular fibrillation following coronary occlusion. Administration of propranolol in sufficient quantity to block the betaadrenergic nervous receptors reinstates fibrillation. It is concluded that the sympathetic division of the autonomic nervous system normally projects a beneficial activity to the myocardium; however, no sympathetic innervation (as in beta-receptor blockade) or increased sympathetic activity (as in the anxious or excited animal) have a detrimental effect on the stability of the ischemic heart, and ventricular fibrillation occurs. The electrophysiologic changes which occur during the first twenty minutes (the period of reversible injury) of ischemia provide interesting results. Rapid alterations seem to occur approximately during the second minute and the tenth minute of ischemia, which correspond to periods of excessive instability of the heart. This is most evident in the increased amplitude of bipolar potentials from the outer layers of the ischemic ventricular wall and the larger S-T segment elevations. The importance of these findings with regard to the almost national epidemic of coronary heart disease and sudden death is discussed.
Analog computer simulation of selected pulmonary function tests
(1975) Olender, Mark Francis; Clark, John W.
A mathematical model previously derived by Golden, et al, (1973) is developed and extended to allow for the simulation of a wide range of pulmonary function tests. The model parameters include large airway resistance, small airway resistance, collapsible airway resistance, collapsible airway compliance, and lung compliance. And, the model is driven by a varible pleural pressure waveform. The simulation is implemented on an analog computer for ease of parameter manipulation. The effects of changes in model parameters on selected pulmonary function tests are observed and discussed. Simulations of diseased states (emphysema, asthma, and fibrosis) are presented and analyzed. It is concluded that the model properly simulates breathing maneuvers associated with the clinical assessment of pulmonary function. In addition the model structure is much simpler than the ventillatory system models of Fry (1968) and Pardaens, et al, (1972), yet yields the same information in a diagnostic sense.
Analog simulation of left ventricular bypass mode control
(1974) Anderson, Candace Marie; Clark, John W.
The subject of this study is optimal mode control for the left ventricular bypass pump used to assist the failing heart. A mathematical model has been formulated for the overall cardiovascular system, both with and without bypass assistance. The closed-loop, uncontrolled model of the unassisted circulation has been implemented on an analog computer, and has been demonstrated capable of simulating normal as well as abnormal physiological behavior. Implementation of the bypass pump model has been shown to produce the general expected hemodynamic effects of decreasing pressure in the left atrium, while increasing that in the systemic arterial load. Four logical modes of pump control have been described and compared on the basis of their effect upon a scalar performance index used to reflect the basic goals of cardiac assistance.
Design and development of a combined cardiovascular assist system for support in severe ventricular failure
(1979) Peterson, Robert L.; Clark, John W.
This thesis work documents the design and testing of a ventricular assist system combining intra-aortic balloon pumping (IABP) with partial veno-arterial bypass (VABP), both pulsatile and nonpulsatile. A series of animal experiments was carried out after verification of the concept on a mock circulation. Although statistical significance was not obtained, the results were encouraging. This system combines the beneficial features of the two devices in a synergistic manner to obtain a system capable of total body support while at the same time improving the viability of the damaged myocardium. IABP, itself incapable of supporting the circulation in severe heart failure, is used to reduce the afterload caused by VABP, which can provide more profound circulatory assistance. Diastolic augmentation by pulsatile VABP enhances that due to IABP, and there is further enhancement of IABP function due to increased mean arterial pressure. A decrease in heart preload pressure was seen which reflected the decreased venous return brought about by bypass. Thus, in spite of increased total body perfusion, cardiac output was diminished. The decrease in cardiac output was sufficient to reduce heart flow work even though there was an increase in afterload pressure. Finally, the state of the animal seemed to be improved by the assist system in that arrhythmia and mortality were decreased during combined assistance.
Microprocessor control of a combined assist system for the profound support of the failing heart
(1979) Philippe, Edouard A.; Clark, John W.; Walker, William F.; Parks, Thomas W.
Conventional non-invasive mechanical circulatory assist methods such as intra-aortic balloon pumping are of little effectiveness in cases of severe ventricular failure. The proposed study is concerned with the development and testing, on a mock circulatory loop and in a series of dog experiments, of an automated combined assist system for the profound support of the failing heart. This system is mildly invasive and consists of the synergistic use of intra-aortic balloon pumping and partial veno-arterial bypass. Previous in vivo studies using this system with no automation have shown that it is quite effective in achieving its clinical objectives, and our purpose is to investigate the ability of the control systems developed herein to match the optimal manual setting of the assist system. The end result of the project is a portable compact automatically controlled ventricular assist system that can be rapidly and easily instituted, thus improving the chance of survival and recovery of acute myocardial infarction and cardiogenic shock victims.
Modeling CICR in rat ventricular myocytes: voltage clamp studies
(BioMed Central, 2010) Krishna, Abhilash; Sun, Liang; Valderrábano, Miguel; Palade, Philip T.; Clark, John W.
Background: The past thirty-five years have seen an intense search for the molecular mechanisms underlying calcium-induced calcium-release (CICR) in cardiac myocytes, with voltage clamp (VC) studies being the leading tool employed. Several VC protocols including lowering of extracellular calcium to affect Ca2+ loading of the sarcoplasmic reticulum (SR), and administration of blockers caffeine and thapsigargin have been utilized to probe the phenomena surrounding SR Ca2+ release. Here, we develop a deterministic mathematical model of a rat ventricular myocyte under VC conditions, to better understand mechanisms underlying the response of an isolated cell to calcium perturbation. Motivation for the study was to pinpoint key control variables influencing CICR and examine the role of CICR in the context of a physiological control system regulating cytosolic Ca2+ concentration ([Ca2+] myo ). Methods: The cell model consists of an electrical-equivalent model for the cell membrane and a fluid-compartment model describing the flux of ionic species between the extracellular and several intracellular compartments (cell cytosol, SR and the dyadic coupling unit (DCU), in which resides the mechanistic basis of CICR). The DCU is described as a controller-actuator mechanism, internally stabilized by negative feedback control of the unit's two diametrically-opposed Ca2+ channels (trigger-channel and release-channel). It releases Ca2+ flux into the cyto-plasm and is in turn enclosed within a negative feedback loop involving the SERCA pump, regulating[Ca2+] myo . Results: Our model reproduces measured VC data published by several laboratories, and generates graded Ca2+ release at high Ca2+ gain in a homeostatically-controlled environment where [Ca2+] myo is precisely regulated. We elucidate the importance of the DCU elements in this process, particularly the role of the ryanodine receptor in controlling SR Ca2+ release, its activation by trigger Ca2+, and its refractory characteristics mediated by the luminal SR Ca2+ sensor. Proper functioning of the DCU, sodium-calcium exchangers and SERCA pump are important in achieving negative feedback control and hence Ca2+ homeostasis. Conclusions: We examine the role of the above Ca2+ regulating mechanisms in handling various types of induced disturbances in Ca2+ levels by quantifying cellular Ca2+ balance. Our model provides biophysically-based explanations of phenomena associated with CICR generating useful and testable hypotheses.
Nonlinear Dynamics in Atomic Force Microscopy for Various Excitation Conditions
(2015-05-11) Huang, Wei; Dick, Andrew J.; O' Malley, Marcia K.; Clark, John W.
The atomic force microscopy (AFM) is a high-resolution measurement tool for measuring sample topography and material properties in micro-scale and nano-scale research. The dynamics of the cantilever probe in AFM is influenced by the intrinsically nonlinear interaction between the probe tip and the surface of the sample. Previous work has shown that in off-resonance excited intermittent-contact AFM, a period-doubling bifurcation can occur as a result of the nonlinearity. The amplitude of the resulting sub-harmonic frequency component of the response has been identified as a source of contrast to measure the Young's modulus of the sample. This dissertation details the continued work in this area and includes three parts. In the first part, the focus is to investigate the performance of a material characterization method, proposed to use the relationship between the sample modulus and the sub-harmonic frequency component, to study material property transitions for one-dimensional samples. In the second part, the focus is on the effect of the inclusion of the explicit dissipative interaction force in the system model on the numerical simulation on the AFM. Both resonant and off-resonant excitation conditions are discussed. In the third part, the focus is on the generation of the sub-harmonic amplitude for an unique dual-frequency excitation condition. The influence of this excitation condition is numerically investigated and experimental studies are conducted with a macro-scale constrained cantilevered beam system to qualitatively verify the numerically predicted behavior. The work in this dissertation brings a wider understanding for these nonstandard excitation methods and their applications in AFM.
Point process models for discharge patterns of single units in the lateral superior olive of the cat
(1985) Linebarger, Darel Allen; Johnson, Don H.; Clark, John W.; Pfeiffer, Paul E.
Discharge patterns from the Lateral Superior Olive of the cat are analyzed using point process methods. An intensity description is developed for responses to continuous tone and tone burst stimuli. The statistics of each process are described using the intervals between events in the response. We find that a first order Markovian model is sufficient to describe the observed serial dependence of the inter-spike intervals. In our model, the duration of the absolute dead time of one interval is inversely related to the duration of the previous interval. Superposition of renewal processes with a dead time implemented is shown to lack the necessary serial dependence which would qualify it as a potential model for LSO discharge patterns. Using our model, the early, non-stationary portion of tone burst responses is predicted based on the statistics of the later, stationary portion.
Potential fields from cardiac strands of cylindrical geometry
(1984) Ganapathy, Nirmala; Clark, John W.; Glantz, Raymon M.; Figueiredo, Rui J. P. de
This paper deals with the classical forward and inverse volume conductor field problems associated with the isolated active cardiac strand. The Purkinje fiber and the atrial trabeculum are chosen as specific examples of cardiac tissue that may be well modeled by cylindrical geometry. The electrical behavior of these strands is modeled in terms of the electrical activity of an equivalent single cell, with a representative membrane that separates an anisotropic intracellular medium from an isotropic extracellular medium. The isolated single atrial muscle fiber is also studied as an interesting special case. A Potential theory model is developed for the strand, that is based on a solution of Laplace's equation in the media of interest, subject to appropriate boundary conditions. The solution for potential at an arbitrary point in the extracellular medium is in the form of a Fourier integral; the equation is subsequently reformulated into a more convenient computational form using a discrete Fourier transform (DFT) method. Implementation of this method using a Fast Fourier Transform (FFT) technique, results in a fast and efficient numerical algorithm for the calculation of volume conductor potentials. A benefit of this approach is that the classical forward and inverse problems in electrophysiology may be viewed as equivalent filtering problems. Thus not only can volume conductor field potentials at varions distances from the strand be easily and rapidly computed, but given field potential data, good estimates of the action potential waveform can also be obtained provided the signal to noise ratio is adequate.
Sensitivity analysis and parameter identification for a model of left ventricular mechanics and the systemic arterial load
(1982) Paulsen, Robert Alan; Clark, John W.; Johnson, Don H.; Walker, William F.
An identification scheme for the determination of several parameters associated with a third-order lumped-parameter model of the systemic arterial system has been developed previously (1). In the present study, a parameter sensitivity analysis of this model is conducted in conjunction with the identification scheme. This analysis indicates that the state variables of this system are not unduly sensitive to changes in the model parameters or initial conditions. It also indicates the relative sensitivities of the individual model parameters and provides valuable insight into the behavior of the arterial model. This insight resulted in a significant simplification of the identification scheme (1) that makes it more likely to be employed in practice. The arterial model mentioned above is driven by aortic root flow f (t), and this waveform is approximated by either of two methods, one involving the measurement of left ventricular pressure, the other a measurement of left ventricular volume. Adequate specification of the model driving waveform f (t) is very important to the identification process and, therefore, the abilities of the aforementioned methods in approximating fa(t) under practiced measurement conditions are investigated. The left ventricular mechanics for an individual patient are specified by the elastance curve in this study. Two clinical approaches, the direct and the indirect, to the estimation of left ventricular elastance are presented. A multiple measurement technique is used to solve for end-diastolic volume in the direct problem and an approximate method for the determination of the aortic valve resistance is suggested for the solution of the indirect problem. A sensitivity analysis of the left ventricular model proved useful in the analysis of both approaches.
Surface reconstruction and display of left ventricular function for pet images
(1984) Kehtarnavaz, Nasser; Figueiredo, Rui J. P. de; Clark, John W.; Zygouakis, Kyriacos
A recently developed camera referred to by the name PET (Positron Emission Tomography) allows the biochemical activity associated with an organ inside the body to be viewed without surgical intervention. The organ considered for the present study is the heart and the goal of the thesis is to aid detecting the coronary artery diseases at an early stage. For this purpose, a three dimensional object of the left ventricle is formed from an available set of two-dimensional image slices generated by PET. An automatic boundary detection algorithm outlines the object surface and assigns appropriate intensity values to the surface points. The surface is then rotated with the long axis of the heart in a vertical position, allowing the myocardium to be viewed from different angles around the heart. Such a display of activity is shown to be an effective way of presenting the functional behavior of the myocardium.
Surface reconstruction from surface contours
(1983) Simar, Laurence Ray; Figueiredo, Rui J. P. de; Clark, John W.; Dufour, Reginald J.
Surface reconstruction from surface contours has become increasingly important in the medical field. Given a set of serial cross sections, it is shown that a structural technique of reconstruction can be developed. The motivation is to analyze the structure of the cross sections so as to represent the surface more faithfully than conventional techniques. The procedure involves syntactic and semantic techniques which allow the algorithm to analyze the cross sections at a high level. This information can then be used to recognize features on adjacent contours and then reproduce the surface which generated the cross sections.
The analysis of multicomponent exponential decay curves
(1974) Thomasson, William Michael; Clark, John W.
There are four basic classes of methods of analyzing exponential decay curves: graphical methods, iterative fitting methods, algebraic fitting methods, and transform methods. Representative types of all these methods are examined in detail as to their approach to computing exponents and their theoretical strengths and weaknesses. A comparison is made of the methods on simulated data and a survey of the reported accuracy of the methods in the literature is used to illustrate these strengths and weaknesses. Consequently, a three-method sequential identification scheme utilizing the graphical curve-peeling method, the DFT (Discrete Fourier Transform) deconvolution method [a new method developed for this study], and the iterative weighted nonlinear leastsquares method is developed for application to real physical data. A series of four examples of the application of the sequential identification scheme is made for physiological data containing from two to four exponents. The intrinsic difficulties of exponential analysis are illustrated, and the utility of the sequential identification scheme is shown.

Browsing by Author "Clark, John W."

Results Per Page

Sort Options