Biomedical subjects

G M Saidel

Publications and source records attributed to G M Saidel.

At least 37 records · Page 2Linked to original sources

PubMed1994

CO2 control of breathing: parameter estimation and stability evaluation.

A method is developed to evaluate system stability for the CO2 control of breathing in individuals by using data from the dynamics of CO2 rebreathing and elimination. The theoretical basis of the method is a physiological model of the CO2 respiratory control system and an explicit stability index (SI). The SI is algebraically related to the model parameters: system volume (Vs), cardiac output (Q), circulatory transit time (ts), and controller gain (G). A sequential optimization scheme is shown to yield estimates of the model parameters by comparing the alveolar ventilation and PCO2 of the model output with corresponding experimental data. Model simulation of CO2 rebreathing and elimination with different parameter values demonstrate that all parameters except ts have significant effect on the outputs. Least-squares estimation of the parameters using model-generated data with added noise showed good precision for all parameters (except ts). This analysis is performed with parameter values chosen to produce overdamped and underdamped responses that would occur in normal and abnormal respiratory control systems, respectively. It is anticipated that SI values of the (overdamped) normal and (underdamped) abnormal systems differ by much more than the variation produced by imprecision of the parameter estimates. For this circumstance, the method is expected to be sensitive enough to distinguish normal from abnormal CO2 respiratory control of individual subjects.

Carbon Dioxide↗

PubMed1994

Mathematical model of acetylcholine kinetics in neuroeffector junctions.

Acetylcholine (ACh) kinetics in neuroeffector junctions (NEJ) of the sinus node plays a key role in vagal control of heart rate. Prior studies have shown that the concentration of ACh ([ACh]) in NEJ appears to follow first-order linear kinetics. To find out the reason why, we examine mathematically diffusion, degradation, and receptor binding of ACh in NEJ. We identify seven conditions that potentially influence ACh kinetics. Because these conditions are satisfied for NEJ in the sinus node, 1) the nonlinearity of ACh binding to muscarinic receptors has little effect on [ACh]; 2) [ACh] does not depend on the distribution of acetylcholinesterase between the interstitial space and the pacemaker cells; 3) the interval from trough to subsequent peak [ACh] at the pacemaker cells is negligible; 4) the mean [ACh] at the pacemaker cells is proportional to the frequency of vagal activity multiplied by the amount of ACh released per vagal stimulus and divided by the rate coefficient of ACh degradation; and 5) [ACh] at pacemaker cells nearly follows first-order linear kinetics but does not at other sites in the NEJ. We conclude that earlier studies showed that [ACh] follows first-order linear kinetics, because they predicted [ACh] only at pacemaker cells. ACh kinetics at other sites in the NEJ, such as at nerve endings, is different.

Acetylcholine↗

PubMed1994

Relative significance of endothelium and internal elastic lamina in regulating the entry of macromolecules into arteries in vivo.

A role for the internal elastic lamina (IEL), which separates the intima and media of an artery wall, as a restrictive barrier to macromolecular movement has been suggested in atherosclerotic lesion development or restenosis during angioplasty. The permeability coefficient of the IEL, however, has never been quantified in unperturbed vessels in vivo. Using a newly developed technique, we measured the concentration distributions in both intima and media of cationic (pI approximately 8.5) and anionic (pI approximately 6.3) isozymes of the 44-kD macromolecule horseradish peroxidase (HRP). Two mathematical models of arterial wall transport differing in their resolution of the intima were required to simulate the concentration distribution data and to estimate the parameters of interest. Optimal estimates of the permeability coefficients of the endothelium (PE) and IEL (PIEL) to HRP were determined by the best least-squares fit of the two models to experimental data. These estimates (anionic: PE = 0.050 +/- 0.021 microns/min, PIEL = 0.146 +/- 0.082 microns/min, n = 8; cationic: PE = 0.034 +/- 0.018 microns/min, PIEL = 0.110 +/- 0.047 microns/min, n = 8) indicate that the IEL is responsible for approximately 25% (anionic, 26 +/- 9%; cationic, 25 +/- 13%) of the resistance to HRP transport from the blood into the arterial media. Although both parameters were less for the cationic preparation, the differences were not significant, and the relative role of the IEL was similar for both molecules.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Validation of continuous thermal measurement of cerebral blood flow by arterial pressure change.

A thermal measurement system to monitor cerebral blood flow (CBF) continuously from the cortical surface is evaluated in vivo. It has a temperature resolution of better than 0.001 degrees C (1 m degrees C) and can compensate for baseline temperature fluctuations in the brain tissue. A new approach has been developed to test the capability of monitoring dynamic CBF response. Transient CBF changes associated with changes in mean arterial blood pressure (MABP) caused by repeated bolus norepinephrine injections are used to examine the response of the measurement system in both the heated mode, sensitive to flow, and the unheated mode, sensitive only to temperature. Experiments on 13 rats demonstrate that changes in the MABP are closely correlated with those of temperature difference in the heated mode. Regression analysis shows a mean slope of 0.9 m degrees C/mm Hg in the heated mode, which is significantly different from zero (p < 0.002) and from the mean slope in the unheated mode (p < 0.002). This indicates that flow signal in the system output can be distinguished from the baseline thermal fluctuations. Thus, the system can be used to detect and study dynamic perfusion changes from the brain surface with minimal tissue damage. Furthermore, analysis of the data shows that the transient flow signal before autoregulation is linearly correlated with changes in MABP.

Animals↗

PubMed1992

Estimation of electrotonic parameters of neurons using an inverse Fourier transform technique.

The objective of this paper is to estimate the passive electrotonic parameters of hippocampal granule cells. Accurate estimation of these parameters is important in understanding the information processing of neurons. A shunt cable model, where the somatic and dendritic time constants can be different, is used to describe the potential changes in the soma and along the dendritic tree. For this model, parameter values are estimated by nonlinear least-squares fitting of the model output to the voltage response of the stimulated cell to current pulses. The solutions are obtained in a two-step process: First, the sensitivity functions are derived from the Laplace transform solution of the theoretical model. Second, the time domain solutions are obtained numerically by an inverse FFT. A sensitivity analysis indicates that accurate estimates require the use of a short current pulse injected at the soma and the sampling of the voltage response close to the end of that pulse. This parameter estimation procedure has been tested on hippocampal granule cells. It yields accurate estimation of neural parameters and will be a useful tool for measuring passive properties of neurons.

Animals↗

PubMed1992

Vascular injury by endotoxin: changes in macromolecular transport parameters in rat aortas in vivo.

Vascular injury can lead to enhanced macromolecular transport into the arterial wall. We previously demonstrated that lipopolysaccharide (LPS) -induced injury to rat aorta in vivo caused increases in intimal and medial horseradish peroxidase (HRP) accumulation. In the present study, we quantitatively interpret these LPS-induced changes in HRP transport parameters. The parameters of interest are the permeability (PL) of the luminal blood-tissue boundary (combination of endothelium and internal elastic lamina, IEL), the effective diffusivity (D), and the convective velocity (V) across the media. The parameter values that yield the best fit of the model to the data provide a basis for understanding the tissue changes. The time of peak transmural (medial) accumulation (24 h after LPS injection) correlated with increases in PL (peak, 12-48 h) and preceded the maximum increase in V (peak, 36 h). The monotonic increase in the intimal accumulation during the 5 days after the injury has a time course distinct from the transient increases in PL and from the changes in D, which implies that endothelial permeability has only limited influence on transport beyond the intima. These data implicate the IEL as a barrier to macromolecular transport in the normal aorta and demonstrate that the endothelium and IEL work in concert to determine intimal macromolecular accumulation.

Animals↗

PubMed1992

Role of the diaphragm in chest wall mechanics.

We analyzed three different assumptions about diaphragm function that determine the thoracoabdominal interaction. In the simplest case, the diaphragm is assumed to be a completely flaccid membrane serving only to partition the thorax and the abdominal cavity. In the second case, it is assumed to have a finite tension but to maintain a relatively flat surface at the base of the rib cage (i.e., a negligible zone of apposition). In the general case, it is assumed that the diaphragm has finite tension and its position may vary (i.e., permitting a zone of apposition). These possible modes of behavior are incorporated into a mathematical model of ventilatory system mechanics that distinguishes the diaphragm, lung, abdomen, and rib cage. The significance of these modes is examined with respect to data from human experiments in which gas or liquid is introduced into the pleural or abdominal spaces, causing a volume change (Vep). We show that the Vep effect on the thoracic and abdominal volumes is sensitive to diaphragm mechanics and depends on the nature of the Vep: gastric distension (with water or air) or pneumothorax. Only the behavior of the general model is consistent with physiological observations, especially the distribution of Vep. Our general mathematical model can quantitatively predict this behavior.

Diaphragm↗

PubMed1991

Noninvasive estimation of cardiac output with nonprescribed breathing.

A noninvasive method to estimate cardiac output Q without special patient cooperation was developed by modifying a previous acetylene-helium (C2H2-He) rebreathing technique (ART). Estimation of Q using ART is based on a single-compartment model that is valid only under prescribed breathing; e.g., fast, deep breathing, and emptying of the rebreathing bag on each breath. To make the ART less dependent on subject cooperation, a more sophisticated mathematical model and estimation method are needed. For this purpose, we modeled the C2H2 and He concentration dynamics at the mouth over successive breaths using a multi-compartment model. This model takes into account the effects of breathing pattern, compartmental volumes, and gas solubility. From computer simulations and sensitivity analysis, we found that Q could be estimated from the available data with adequate precision. Our model and estimation method were tested on a group of six normal adult subjects, at rest and during submaximal exercise (75 watts). Estimates of Q from our new method (6.5 +/- 0.4 L/min at rest, 12.5 +/- 0.4 L/min at 75 watts) were in agreement with those obtained using a previous ART (7.0 +/- 0.3 L/min at rest, 12.6 +/- 0.5 L/min at 75 watts). We conclude that this approach promises to provide reliable estimates of Q in patients (e.g., children and elderly), at rest and during exercise, without the need of prescribed breathing patterns or changes in rebreathing bag volume.

Acetylene↗

PubMed1991

Sensation and control of breathing: a dynamic model.

A dynamic model of the CO2 respiratory control system is proposed, which can provide a qualitative basis for predicting breathing sensations. The discomfort index, which represents breathing sensations, is assumed to be composed of two sources: the arterial CO2 level and the respiratory motor command. The respiratory controller receives inhibitory neuromechanical and excitatory CO2 signals from the plant. The CO2 signal is enhanced by exercise stimuli. This dynamic multiplicative-type controller is used in simulations of key experiments: exercise and CO2 rebreathing with and without resistive loading. The dynamics of the discomfort index, the respiratory motor command, ventilation, and arterial CO2 concentration conform to the experimental data. The perceptual sensitivity to CO2 relative to respiratory effort is significantly correlated with the slope of hypercapnic ventilatory response. This result shows a clear linkage between ventilatory response and breathing sensations. Although it is shown that the automatic controller effectively minimizes the discomfort index for perturbations about an operating point under certain conditions, the discomfort index itself does not seem to be an underlying control principle of the proposed automatic controller model. Rather, breathing sensations may influence ventilatory responses by modifying the output of the automatic controller.

Carbon Dioxide↗

PubMed1991

Optimal design of experiments to estimate LDL transport parameters in arterial wall.

To quantify transport processes in atherosclerosis, the arterial wall is often exposed to labeled lipoproteins. In vivo experiments are desirable for estimation of transport parameters, but they are technically difficult. A dynamic mass transfer model has been developed to describe experimental transmural profiles of lipoprotein accumulation as a function of luminal permeability, diffusion, convection, and degradation. To avoid extraneous experiments and to assure successful parameter estimation, an optimal design of experiments is needed. For our purposes a design was considered optimal when it maximized the sensitivity of the model output to changes in parameter values as indicated by the determinant of the Hessian matrix of the objective function. A comparison was made between two designs: dual-time designs prescribing unequal circulation times for two distinguishable injections of labeled low-density lipoprotein (LDL) and dual-species designs requiring simultaneous circulation of LDL and tyramine-cellobiose-modified LDL. Circulation time was optimized for both designs. Although both were heavily dependent on the circulation times, dual-time designs required better preliminary knowledge of parameter values. Because labeled degradation products of the modified tracer become anchored in the arterial tissue, information about the degradation process is retained in the dual-species study. For this reason, dual-species designs were generally superior to dual-time designs.

Animals↗

PubMed1991

Contribution of large airway to the input impedance of the respiratory system.

To evaluate the contribution of the large airway to total respiratory impedance, we develop a one-dimensional model of pressure and flow in these airways by coupling conservation of mass and momentum equations with the geometric information obtained by the acoustic reflection technique. We use this model to calculate the impedance of the respiratory system distal to the carina from impedance data estimated at the airway opening by the forced oscillation technique. Simulations show that the real part of the impedance distal to the carina is uniformly decreased from the impedance at the airway opening, indicating a resistive loss, while the imaginary part is increased as a function of frequency. We estimate parameter values for a six-parameter two-compartment lung model and for a three-parameter reduction of this model before and after the application of the upper airway data to the impedance spectrum. Although compliance terms seem to be minimally affected by the manipulation of the data, resistance and inertance terms are influenced in a fashion that suggests that the resistive contribution of the upper airway to total respiratory impedance is significant. Furthermore it appears that the elastic nature of the walls of the upper airway also impact on estimates of total respiratory impedance at the airway opening.

Airway Resistance↗

PubMed1990

Nonlinear parameter estimation applied to a model of smooth pursuit eye movements.

We present a procedure that optimally adjusts specified parameters of a mathematical model to describe a set of measured data. The technique integrates a dynamic systems-simulation language with a robust algorithm for nonlinear parameter estimation, and it can be implemented on a microcomputer. Sensitivity functions are generated that indicate how the operation of the model is affected by each updated parameter. This procedure offers a greater resolution of optimal parameter values than other, less rigorous methods. To illustrate this technique we have applied it to the model of human smooth pursuit eye movements proposed by D.A. Robinson and colleagues (1986).

Eye Movements↗

PubMed1990

Mathematical model of chest wall mechanics: a phenomenological approach.

A mathematical model of chest wall mechanics, based on a phenomenological approach to force balances, provides a quantitative framework for analyzing many types of chest wall movements by using orthogonal displacement coordinates. The moveable components of the ventilatory system include the rib cage, diaphragm, and abdomen. A distinction is made between the lung-apposed and diaphragm-apposed actions on the rib cage. The model equations are derived from "pressure" balances and geometrical relations of the compartments; the stress-displacement relations are hyperbolic. With this model we simulated stiff and flaccid chest wall behavior under normal and constrained conditions associated with abdominal compression, a Mueller maneuver, and a diaphragmatic isometric inspiration. We also examined situations that produce paradoxical as well as orthodox inspiratory movements. The results of these simulations were quantitatively consistent with available data from the literature. A phenomenon predicted by the stiff-wall model during quasi-static inspiration is that the rib cage displacement is negligible near residual volume, but then increases dramatically with lung volume. Since this mathematical model has a sound physical basis and is more comprehensive than previous models, it can be used to predict and analyze the behavior of the chest wall under a wide variety of circumstances.

Abdominal Muscles↗

PubMed1990

Pressures generated by rib cage and abdominal compressions during cardiopulmonary resuscitation.

When the rib cage and abdomen are compressed during cardiopulmonary resuscitation (CPR), the effect on intrathoracic pressure, and therefore on haemodynamics, cannot be quantitatively predicted without a physiologically based mathematical model of chest wall dynamics. Using such a model, we compared model simulations of pleural Ppl and abdominal Pab pressures with those from dog experiments in which the compression of the rib cage was delayed from 0 to 500 ms after compression of the abdomen. Integrals of Ppl and transdiaphragmatic pressure, Pdi = Pab-ppl, over their positive and negative values during a cycle were chosen as indices of driving pressures for cardiac output. Both from the model output and experimental data, we found that the positive ppl integral PPI tends to increase with a longer delay between rib cage and abdominal compressions. The negative ppl integral NPI, however, tends to decrease according to the model predictions and data. Furthermore, the positive and negative integrals of Pdi also tend to change with delay time in the opposite way, as shown by both the model simulations and the experiments. Our results show that chest wall tissues modify the externally applied pressures, thereby not allowing us to use the externally applied pressure sources directly as the driving pressure of the cardiovascular system under study. The optimal conditions for haemodynamics during CPR require a compromise between the positive and negative integral indices. Prediction of the optimal haemodynamics from externally applied pressures requires the coupling of appropriate physiological models of chest wall dynamics and haemodynamics.

Abdomen↗

PubMed1990

Control and evaluation of high-frequency jet ventilation: mechanical lung model.

Ventilation systems that operate at high-frequency and deliver small volumes have the potential to provide adequate alveolar ventilation without excessive pulmonary pressures. One way of producing high-frequency ventilation is by use of jet bursts of an input gas through a cannula controlled by a solenoid valve. This high-frequency jet ventilation has yet to be quantitatively analysed for optimal clinical use. From an analysis of the jet-producing device, we obtained a quantitative relationship which allowed us to predict the gas volume of a jet burst (Vjet) from the driving pressure (Pd), and the jet duration (tI). The device was applied to a mechanical lung model (a tube attached to an elastic bag corresponding to the lung airway and alveolar space). We examined how the control variables of the jet ventilation system changed the bag (alveolar) volume with respect to Vjet, the volume of entrained gas, and the volume of shunted gas. Using a nitrogen washout analysis, we evaluated the operating lung volume, effective dead-space volume (Veds), and effective ventilation rate (Veff). We found that Veds is independent of the individual effects of jet cycle frequency, duty cycle, cannula diameter, and entrainment fraction. While Veds was not affected significantly by the shape of the airway, it did depend on the distance of the jet cannula tip to the ventilated bag (or alveolar region) and on the tidal volume.

Biomechanical Phenomena↗

PubMed1990

Optimal design of a thermistor probe for surface measurement of cerebral blood flow.

Microthermistors are put on the surface of cerebral cortex to monitor local cerebral blood flow (CBF) continuously with minimal tissue damage and disturbance to the normal physiological state. Using a distributed, dynamic model of the measurement system, we simulated the effects of this flow measurement method under isothermal and adiabatic boundary conditions. Numerical results show that the adiabatic boundary condition can provide maximal sensitivity to perfusion changes at physiological perfusion levels. The constant power and constant temperature operating modes are compared in terms of output relation, sensitivity, and frequency response through analytical and numerical solutions. While the steady-state relations between thermistor measurements and perfusion for the two modes do not differ significantly, the constant temperature mode has better frequency response. Analytical results show that the relative sensitivity is the same for the two modes and is approximately proportional to the radius of thermistor. If there is an unperfused layer surrounding the thermistor, the sensitivity will decrease as the thickness of the layer increases. Simulations predict that the thermal measurement has a low-pass frequency response and the cutoff frequency is inversely proportional to the probe surface area. The results provide a theoretical foundation to the optimal design of thermistor probe for continuous CBF measurement from tissue surface.

Cerebrovascular Circulation↗

PubMed1990

Temperature and albumin effects on adsorption of bilirubin from standard solution using anion-exchange resin.

The efficacy of plasma bilirubin sorption for the treatment of patients with hepatic dysfunction can be determined by a quantitative evaluation of bilirubin adsorption. The objective of this study is to examine the effects of temperature (4-42 degrees C) and albumin concentration (0.5-5.0 g%) on bilirubin removal from solution by an anion-exchange resin. For a constant albumin concentration, adsorption increased with temperature. The adsorption isotherm curves did not show saturation at the lower temperatures. At a constant temperature, adsorption increased with decreasing albumin concentration. A one-parameter model was used to describe the data for bilirubin adsorption at all temperatures and for all initial concentrations of bilirubin and albumin. This parameter increased monotonically with temperature and decreased monotonically with albumin concentration. From a practical clinical point of view, bilirubin sorption may be increased by operation of the sorbent column at above ambient temperature.

Adsorption↗

PubMed1990

Radial heat and water transport across the airway wall.

The thermal profiles in the airways of healthy human volunteers and patients with asthma differ after cessation of hyperpnea. The asthmatic patients rewarm their airways more rapidly. To identify thermal properties and processes that could account for the difference between these populations, we developed a model describing the radial transport of heat and water across the trachea. A distinctive feature of the model is a variable parameter describing blood supply to the mucosal and submucosal layers. Simulations performed with the model are initiated by a breath-hold maneuver and are propagative in time. Blood perfusion rates in the airway wall, the thickness of the layer of airway surface liquid, and the mucosa-submucosa thickness, all thought to be more pronounced in asthmatic patients, were varied by changing model parameters and initial conditions. Increasing the thickness of the liquid layer by more than an order of magnitude had little effect on the temperature or water content in the airway lumen. Doubling the blood flow to the mucosa-submucosa resulted in a slight increase in airway temperature. When this effect was coupled, however, with an increase in the thickness of the mucosa-submucosa layer, the increase in temperature was more pronounced. Because the bronchial circulation is the major source of heat to the airway, these results indicate that differences in airway wall thickness coupled with differences in the magnitude or responsiveness of the bronchial microcirculation could account for the differences in intra-airway temperature between the two populations.

Air↗