G. Avanzolini

An integrated model of the human ventilatory control system: the response to hypoxia.

The mathematical model of the respiratory control system described in a previous companion paper is used to analyse the ventilatory response to hypoxic stimuli. Simulation of long-lasting isocapnic hypoxia at normal alveolar PCO2 (40 mmHg=5.33 kPa) shows the occurrence of a biphasic response, characterized by an initial peak and a subsequent hypoxic ventilatory decline (HVD). The latter is about as great as 2/3 of the initial peak and can be mainly ascribed to prolonged neural hypoxia. If isocapnic hypoxia is performed during hypercapnia (PACO2=48 mmHg =6.4 kPa), the ventilatory response is stronger and HVD is minimal (about 1/10-1/5 of the initial peak). During poikilocapnic hypoxia, ventilation exhibits smaller changes compared with the isocapnic case, with a rapid return toward baseline within a few minutes. Moreover, a significant undershoot occurs at the termination of the hypoxic period. This undershoot may lead to apnea and to a transient destabilization of the control system if the peripheral chemoreflex gain and time delay are twofold greater than basal.

A comprehensive simulator of the human respiratory system: Validation with experimental and simulated data

A comprehensive model of oxygen (O2) and carbon dioxide (CO2) exchange, transport, and storage in the adult human is presented, and its ability to provide realistic responses under different physiological conditions is evaluated. The model comprises three compartments (i.e., lung, body tissue, and brain tissue) and incorporates a controller that adjusts alveolar ventilation and cardiac output dynamically integrating stimuli coming from peripheral and central chemoreceptors. A new realistic CO2 dissociation curve based on a two-buffer model of acid-base chemical regulation is included. In addition, the model explicitly considers relevant physiological factors such as buffer base, the nonlinear interaction between the O2 and CO2 chemoreceptor responses, pulmonary shunt, dead space, variable time delays, and Bohr and Haldane effects. Model simulations provide results consistent with both dynamic and steady-state responses measured in subjects undergoing inhalation of high CO2 (hypercapnia) or low O2 (hypoxia) and subsequent recovery. An analysis of the results indicates that the proposed model fits the experimental data of ventilation and gas partial pressures as some meaningful simulators now available and in a very large range of gas intake fractions. Moreover, it also provides values of blood concentrations of CO2, HCO−3, and hydrogen ions in good agreement with more complex simulators characterized by an implicit formulation of the CO2 dissociation curve. In the experimental conditions analyzed, the model seems to represent a single theoretical framework able to appropriately describe the different phenomena involved in the control of respiration.

Quantification of Motor Impairment in Parkinson's Disease Using an Instrumented Timed Up and Go Test

The Timed Up and Go (TUG) test is a clinical test to assess mobility in Parkinsons disease (PD). It consists of rising from a chair, walking, turning, and sitting. Its total duration is the traditional clinical outcome. In this study an instrumented TUG (iTUG) was used to supplement the quantitative information about the TUG performance of PD subjects: a single accelerometer, worn at the lower back, was used to record the acceleration signals during the test and acceleration-derived measures were extracted from the recorded signals. The aim was to select reliable measures to identify and quantify the differences between the motor patterns of healthy and PD subjects; in order to do so, besides comparing each measure individually to find significant group differences, feature selection and classification were used to identify the distinctive motor pattern of PD subjects. A subset of three features (two from Turning, one from the Sit-to-Walk component), combined with an easily-interpretable classifier (Linear Discriminant Analysis), was found to have the best accuracy in discriminating between healthy and early-mild PD subjects. These results suggest that the proposed iTUG can characterize PD motor impairment and, hence, may be used for evaluation, and, prospectively, follow-up, and monitoring of disease progression.

CADCS simulation of the closed-loop cardiovascular system

A pulsatile simulator of the closed-loop cardiovascular system, designed to solve simulation, identification and control problems in a research and education context, is presented. Its implementation makes use of a command-driven interactive program for simulation of non-linear ordinary differential equations. The flexibility of the simulator is demonstrated by the results presented which refer to a basal steady-state circulatory condition as well as a transient induced by an abrupt change in peripheral resistance.

A new approach for tracking respiratory mechanical parameters in real-time

A new recursive least-squares procedure for on-line tracking of changes in viscoelastic properties of respiratory mechanics is proposed and applied to artificially ventilated patients. Classical least-squares methods based on simple first-order linear models with time-constant parameters generally provide systematic residuals that hardly satisfy standard statistical tests for model validation in terms of residuals. On the other hand, high order and/or nonlinear models introduce parameters whose estimates are of difficult interpretation in a clinical context. The present procedure overcomes these limitations by using the well-known first-order model of respiratory mechanics, wherein variability of resistance and elastance during the breathing cycle is allowed to take into account nonlinear and high-order behavior. Mean and standard deviation of resistance and elastance estimates, relative to a respiratory cycle, are then determined recursively. Feasibility of the method is evaluated by applying it both to experimental and simulated pressure-airflow signals measured in an intensive care unit during mechanical ventilation of patients recovering from heart surgery. Results demonstrate that the proposed procedure provides data description satisfying statistical tests, such as residual whiteness, and reliable estimates of viscoelastic lung parameters even during substantial and fast variations in the respiratory status. In addition, unlike classical methods, the new technique provides the means for on-line evaluation of parameter variability during each respiratory cycle, by the estimate of their standard deviations. This is important in clinical practice, because only the knowledge of reliable parameter values and standard deviations enables significant changes in the respiratory viscoelastic characteristics, and thus in patient status, to be assessed.

Real-time tracking of parameters of lung mechanics : emphasis on algorithm tuning

We consider the problem of tracking rapid changes in the viscous and elastic properties of the respiratory system by using mouth flow and transpulmonary pressure data measured during mechanical ventilation. A recursive least-squares algorithm with adjustable compensator is used for online estimation of an R-C model of the breathing mechanics. Specific simulation experiments are presented to provide guidelines to select suitable values for the key variable, which controls the compromise between tracking ability and noise sensitivity. The results obtained confirm the critical role of the optimum tuning in relation to the noise level. Experimental results obtained from data measured on mechanically-ventilated dogs, in which respiratory distress syndrome was intravenously induced by oleic acid, demonstrate that the tuned algorithm is able to track appropriately both the viscous and elastic properties of lung mechanics. Parameter estimates are consistent with those obtained by standard and robust offline algorithms and their time course is in qualitative agreement with known physiopathological behaviour.

Prediction of Solute Kinetics, Acid-Base Status, and Blood Volume Changes During Profiled Hemodialysis

AbstractA mathematical model of solute kinetics oriented to the simulation of hemodialysis is presented. It includes a three-compartment model of body fluids (plasma, interstitial and intracellular), a two-compartment description of the main solutes K+,Na+,Cl- urea, HCO3-,H+), and acid-base equilibrium through two buffer systems (bicarbonate and noncarbonic buffers). Tentative values for the main model parameters can be given a priori, on the basis of body weight and plasma concentration values measured before beginning the session. The model allows computation of the amount of sodium removed during hemodialysis, and may enable the prediction of plasma volume and osmolarity changes induced by a given sodium concentration profile in the dialysate and by a given ultrafiltration profile. Model predictions are compared with clinical data obtained during 11 different profiled hemodialysis sessions, both with all parameters assigned a priori, and after individual estimation of dialysances and mass-transfer coefficients. In most cases, the agreement between the time pattern of model solute concentrations in plasma and clinical data was satisfactory. In two sessions, blood volume changes were directly measured in the patient, and in both cases the agreement with model predictions was acceptable. The present model can be used to improve the dialysis session taking some characteristics of individual patients into account, in order to minimize intradialytic unbalances (such as hypotension or disequilibrium syndrome).

Comparison of algorithms for tracking short-term changes in arterial circulation parameters

Three recursive methods especially suited for identification of systems with rapidly changing parameters are applied to tracking of the viscoelastic properties of the systemic arterial bed. These methods include two least squares (LS) algorithms with constant or variable forgetting factor (RLS and LSVF) and an LS algorithm incorporating both a constant forgetting factor and covariance modification (CFCM). The methods are presented in a unified framework, and their sensitivity with respect to the design variables is investigated using noisy data from computer simulations. All analyzed methods have satisfactorily tracked rapid changes in peripheral resistance. The LSVF method, which offers slightly better performances than the classical RLS, may be preferred when calculation efficiency is the prime requirement. The CFCM algorithm, although maintaining reasonable simplicity, shows the best tracking ability also on varying of the noise sequence.<<ETX>>

Nonlinear mechanisms determining expiratory flow limitation in mechanical ventilation: a model-based interpretation.

AbstractA nonlinear model of breathing mechanics, in which the tracheobronchial airways are considered in three serial segments, is presented to obtain insights into the mechanisms underlying expiratory flow limitation (EFL) in mechanically ventilated patients. Chronic obstructive pulmonary disease (COPD) and normal conditions were simulated and EFL was detected by application of negative expiratory pressure at the mouth or resistance reduction of the expiratory circuit. Simulation results confirm that both techniques reveal remarkable differences in the flow–volume curves between normal subjects and COPD patients, the former showing absence of EFL and the latter exhibiting EFL over most of the expiration. To interpret the role of different nonlinear mechanisms in producing EFL, different flow–volume curves obtained by changing model parameter values were analyzed. An increase in lower-airway resistance did not give rise to EFL, whereas a change in the pressure–volume characteristic of the intermediate-airway segment, towards increased resistance and easier collapse, significantly modified system behavior. In particular, EFL was observed when this intermediate-segment change was combined with an increase in lower-airway resistance. This evidence suggests that modifications, producing loss of radial traction and consequent narrowing of the airways in the peribronchial region, may play a leading role in EFL in COPD patients.

Role of the mechanical properties of tracheobronchial airways in determining the respiratory resistance time course.

AbstractA physiologically based simulation model of breathing mechanics was considered in an attempt to interpret and explain the time course of input respiratory resistance during the breathing cycle, observed in recent studies on ventilated patients. The model assumes a flow-dependent Rohrer resistance for the upper extrathoracic airways and volume-dependent resistance and elastance for the intermediate airways. A volume-dependent resistance describes the dissipative pressure loss in the lower airways, and two constant elastances represent lung and chest wall elasticity. Simulated mouth flow and pressure signals obtained in a variety of well-controlled conditions were used to analyze total respiratory resistance and elastance estimated by an on-line algorithm based on a time-varying parameter model. These estimates were compared with those provided by classical estimation algorithms based on time-invariant models with two, three, and four parameters. The results show that the four-parameter model is difficult to identify, while the three-parameter one offers no substantial advantage for estimating input resistance with respect to the more simple two-parameter model. In contrast, the time-varying approach provides good on-line estimates of the simulated end-expiration and end-inspiration resistances. These values provide further information of potential clinical utility, with respect to time-invariant models. For example, the results show that the difference between the end-expiration and end-inspiration resistance increases when obstructions shift from the upper to the lower airways. The similarity of the results obtained with measured and simulated data indicates that, in spite of its simplicity, the simulation model describes important physiological mechanisms underlying changes in respiratory input resistance, specifically the mechanical properties of intermediate airways.