A simple mathematical model of spontaneous swallow effects on breathing based on new experimental data.

The coordination of respiration and swallowing involves an interaction between two central pattern generators, and this can be disturbed in some pathological situations. To better understand this interaction, we aim in this study to characterize the effect of a spontaneous swallow on the breathing pattern. This is first realized using Respiratory Inductive Plethysmography on 11 healthy subjects. Real signals highlight several mechanisms for swallowing: ending of inspiration, prolongation of expiration or active expiration. These behaviours have been integrated in an existing model of the respiratory system simulating the activity of the respiratory centers, the respiratory muscles, and rib cage internal mechanics. The resulting model of interaction between breathing and swallowing is compatible with the observed effects and is driven for swallowing by a limited number of parameters.

Non-invasive cardiac output monitoring in pharmacology: A plethysmographie solution in rats.

Cardiovascular monitoring is of great importance in pharmacology but there is a lack of convenient non-invasive alternatives. Hence, we aim to evaluate the relevance of inductive plethysmography (IP) in preclinical cardiac studies. An IP system was specifically designed for rat. Its evaluation carried out using a mechanical test bench has shown appropriate instrumental performances for cardiac monitoring in rats. Measurements were also performed during a volume overload hemodynamic challenge in vivo in rats. The cardiac output variation has similar kinetic and amplitude when compared to results of previous studies. This suggests that our system is suitable for cardiac output monitoring in rat.

Empirical mode decomposition of respiratory inductive plethysmographic signals for stroke volume variations monitoring: respiratory protocol and comparison with impedance cardiography.

We investigate Respiratory Inductive Plethysmography (RIP) to estimate cardiac activity from thoracic volume variations and study cardio-respiratory interactions. The objective of the present study is to evaluate the ability of RIP to monitor stroke volume (SV) variations, with reference to impedance cardiography (IMP). Five healthy volunteers in seated and supine positions were asked to blow into a manometer in order to induce significant SV decreases. Time-scale analysis was applied on calibrated RIP signals to extract cardiac volume signals. Averaged SV values, in quasi-stationary states at rest and during the respiratory maneuvers, were then estimated from these cardiac signals and from IMP signals simultaneously acquired. SV variations between rest and maneuvers were finally evaluated for both techniques. We show that SV values as well as SV variations are correlated between RIP and IMP estimations, suggesting that RIP could be used for SV variations monitoring.

Integration of detailed modules in a core model of body fluid homeostasis and blood pressure regulation.

This paper presents a contribution to the definition of the interfaces required to perform heterogeneous model integration in the context of integrative physiology. A formalization of the model integration problem is proposed and a coupling method is presented. The extension of the classic Guyton model, a multi-organ, integrated systems model of blood pressure regulation, is used as an example of the application of the proposed method. To this end, the Guyton model has been restructured, extensive sensitivity analyses have been performed, and appropriate transformations have been applied to replace a subset of its constituting modules by integrating a pulsatile heart and an updated representation of the renin-angiotensin system. Simulation results of the extended integrated model are presented and the impacts of their integration within the original model are evaluated.

A simple dynamic model of respiratory pump.

To study the interaction of forces that produce chest wall motion, we propose a model based on the lever system of Hillman and Finucane (J Appl Physiol 63(3):951-961, 1987) and introduce some dynamic properties of the respiratory system. The passive elements (rib cage and abdomen) are considered as elastic compartments linked to the open air via a resistive tube, an image of airways. The respiratory muscles (active) force is applied to both compartments. Parameters of the model are identified in using experimental data of airflow signal measured by pneumotachography and rib cage and abdomen signals measured by respiratory inductive plethysmography on eleven healthy volunteers in five conditions: at rest and with four level of added loads. A breath by breath analysis showed, whatever the individual and the condition are, that there are several breaths on which the airflow simulated by our model is well fitted to the airflow measured by pneumotachography as estimated by a determination coefficient R(2) > or = 0.70. This very simple model may well represent the behaviour of the chest wall and thus may be useful to interpret the relative motion of rib cage and abdomen during quiet breathing.

Variability of end-expiratory lung volume in premature infants.

BACKGROUND: Analysis of breath-to-breath variability of respiratory characteristics provides information on the respiratory control. In infants, the control of end-expiratory lung volume (EELV) is active and complex, and it can be altered by respiratory disease. The pattern of EELV variability may reflect the behavior of this regulatory system. OBJECTIVES: We aimed to characterize EELV variability in premature infants, and to evaluate variability pattern changes associated with respiratory distress and ventilatory support. METHODS: EELV variations were recorded using inductance plethysmography in 18 infants (gestational age 30-33 weeks) during the first 10 days of life. An autocorrelation analysis was conducted to evaluate the 'EELV memory', i.e. the impact of the characteristics of one breath on the following breaths. RESULTS: In infants without respiratory symptoms, EELV variability was high, with large standard deviations of EELV. Autocorrelation was found to be significant until a median lag of 7 (interquartiles: 4-8) breaths. Autocorrelation was markedly prolonged in patients with respiratory distress or ventilatory support, with a higher number of breath lags with significant autocorrelation (p < 0.01) and higher autocorrelation coefficients (p < 0.05). Conventional assisted ventilation does not re-establish a healthy EELV profile and is associated with lower respiratory variability. CONCLUSIONS: In premature infants, EELV variability pattern is modified by respiratory distress with a prolonged 'EELV memory', which suggests a greater instability of the control of EELV.

On-line monitoring of lung mechanics during spontaneous breathing: a physiological study.

BACKGROUND: Monitoring the mechanics of breathing in patients with advanced chronic obstructive lung diseases prior to lung transplantation is useful to characterize changes in the mechanical properties of the lungs. On-line methods of monitoring immediately process the data for clinical decisions. However, the few available methods are so far limited to monitor respiratory mechanics in ventilator-dependent patients. We investigated whether on-line monitoring of the lung mechanics, including intrinsic PEEP, was feasible in spontaneously breathing patients. METHODS: In 9 stable patients with chronic obstructive pulmonary disease (COPD) and 11 with cystic fibrosis (CF) undergoing the procedure for the lung transplantation waiting list, we applied 2 methods of on-line monitoring (modified recursive least squares, RLS and modified multiple linear regression methods, SLS) of intrinsic PEEP (P(0)), dynamic lung elastance (E(Ldyn)) and inspiratory resistance (R(Linsp)), and compared them with an off-line graphical analysis (GA), our reference technique. RESULTS: In CF patients, there was no difference between methods, while in COPD, the median values of E(Ldyn) and R(Linsp) were significantly different between GA/SLS and GA/RLS, respectively (Dunn's, p<0.05). However, the correlation was very high for all comparisons, particularly for E(Ldyn) (R>0.98) and R(Linsp) (R>0.93). Moreover, Bland-Altman plots showed that the mean differences were consistently low and the intervals of agreement reasonable. CONCLUSIONS: Our study suggests that on-line methods are reliable for monitoring lung mechanics in spontaneous breathing patients with severe lung diseases and could help clinicians in their decision-making process.

Cardiogenic oscillations extraction in inductive plethysmography: Ensemble empirical mode decomposition.

The purpose of this study is to investigate the potential of the ensemble empirical mode decomposition (EEMD) to extract cardiogenic oscillations from inductive plethysmography signals in order to measure cardiac stroke volume. First, a simple cardio-respiratory model is used to simulate cardiac, respiratory, and cardio-respiratory signals. Second, application of empirical mode decomposition (EMD) to simulated cardio-respiratory signals demonstrates that the mode mixing phenomenon affects the extraction performance and hence also the cardiac stroke volume measurement. Stroke volume is measured as the amplitude of extracted cardiogenic oscillations, and it is compared to the stroke volume of simulated cardiac activity. Finally, we show that the EEMD leads to mode mixing removal.

A model of mechanical interactions between heart and lungs.

To study the mechanical interactions between heart, lungs and thorax, we propose a mathematical model combining a ventilatory neuromuscular model and a model of the cardiovascular system, as described by Smith et al. (Smith, Chase, Nokes, Shaw & Wake 2004 Med. Eng. Phys.26, 131-139. (doi:10.1016/j.medengphy.2003.10.001)). The respiratory model has been adapted from Thibault et al. (Thibault, Heyer, Benchetrit & Baconnier 2002 Acta Biotheor. 50, 269-279. (doi:10.1023/A:1022616701863)); using a Liénard oscillator, it allows the activity of the respiratory centres, the respiratory muscles and rib cage internal mechanics to be simulated. The minimal haemodynamic system model of Smith includes the heart, as well as the pulmonary and systemic circulation systems. These two modules interact mechanically by means of the pleural pressure, calculated in the mechanical respiratory system, and the intrathoracic blood volume, calculated in the cardiovascular model. The simulation by the proposed model provides results, first, close to experimental data, second, in agreement with the literature results and, finally, highlighting the presence of mechanical cardiorespiratory interactions.

Calibration of respiratory inductance plethysmograph in preterm infants with different respiratory conditions.

Respiratory inductance plethysmography (RIP) is a method for respiratory measurements particularly attractive in infants because it is noninvasive and it does not interfere with the airway. RIP calibration remains controversial in neonates, and is particularly difficult in infants with thoraco-abdominal asynchrony or with ventilatory assist. The objective of this study was to evaluate a new RIP calibration method in preterm infants either without respiratory disease, with thoraco-abdominal asynchrony, or with ventilatory support. This method is based on (i) a specifically adapted RIP jacket, (ii) the least squares method to estimate the volume/motion ribcage and abdominal coefficients, and (iii) an individualized filtering method that takes into account individual breathing pattern. The reference flow was recorded with a pneumotachograph. The accuracy of flow reconstruction using the new method was compared to the accuracy of three other calibration methods, with arbitrary fixed RIP coefficients or with coefficients determined according to qualitative diagnostic calibration method principle. Fifteen preterm neonates have been studied; gestational age was (mean +/- SD) 31.7 +/- 0.8 weeks; birth weight was 1,470 +/- 250 g. The respiratory flow determined with the new method had a goodness of fit at least equivalent to the other three methods in the entire group. Moreover, in unfavorable conditions--breathing asynchrony or ventilatory assist--the quality of fit was significantly higher than with the three other methods (P < 0.05, repeated measures ANOVA). Accuracy of tidal volume measurements was at least equivalent to the other methods, and the breath-by-breath differences with reference volumes were lower, although not significantly, than with the other methods. The goodness of fit of the reconstructed RIP flow with this new method--even in unfavorable respiratory conditions--provides a prerequisite for the study of flow pattern during the neonatal period.

SAPHIR: a physiome core model of body fluid homeostasis and blood pressure regulation.

We present the current state of the development of the SAPHIR project (a Systems Approach for PHysiological Integration of Renal, cardiac and respiratory function). The aim is to provide an open-source multi-resolution modelling environment that will permit, at a practical level, a plug-and-play construction of integrated systems models using lumped-parameter components at the organ/tissue level while also allowing focus on cellular- or molecular-level detailed sub-models embedded in the larger core model. Thus, an in silico exploration of gene-to-organ-to-organism scenarios will be possible, while keeping computation time manageable. As a first prototype implementation in this environment, we describe a core model of human physiology targeting the short- and long-term regulation of blood pressure, body fluids and homeostasis of the major solutes. In tandem with the development of the core models, the project involves database implementation and ontology development.

SAPHIR - a multi-scale, multi-resolution modeling environment targeting blood pressure regulation and fluid homeostasis.

We present progress on a comprehensive, modular, interactive modeling environment centered on overall regulation of blood pressure and body fluid homeostasis. We call the project SAPHIR, for "a Systems Approach for PHysiological Integration of Renal, cardiac, and respiratory functions". The project uses state-of-the-art multi-scale simulation methods. The basic core model will give succinct input-output (reduced-dimension) descriptions of all relevant organ systems and regulatory processes, and it will be modular, multi-resolution, and extensible, in the sense that detailed submodules of any process(es) can be "plugged-in" to the basic model in order to explore, eg. system-level implications of local perturbations. The goal is to keep the basic core model compact enough to insure fast execution time (in view of eventual use in the clinic) and yet to allow elaborate detailed modules of target tissues or organs in order to focus on the problem area while maintaining the system-level regulatory compensations.

Respiratory inductance plethysmography is suitable for voluntary hyperventilation test.

The aim of this work was to evaluate the goodness of fit of a signal issued of the respiratory inductance plethysmography (RIP) derivative to the airflow signal during rest, voluntary hyperventilation, and recovery. RIP derivative signal was filtered with an adjusted filter based on each subject airflow signal (pneumotachography). For each subject and for each condition (rest, voluntary hyperventilation, and recovery) comparisons were performed between the airflow signal and the RIP derivative signal filtered with an adjusted filter obtained either on rest signal or on the studied part of the signals (voluntary hyperventilation or recovery). Results show that the goodness of fit was : (1) higher than 90% at almost all comparisons (122 on 132), (2) not improved by applying an adjusted filter obtained on the studied part of the signals. These results suggest that RIP could be used for studying breathing during voluntary hyperventilation and recovery using adjusted filters obtained from comparison to airflow signal at rest.

Stroke volume estimation by thoracocardiography is better when glottis is closed.

Thoracocardiography approach pretends to non-invasively monitor stroke volume by inductive plethysmographic recording of ventricular volume curves by a transducer placed on the chest. The purpose of this study was to investigate the potential of thoracocardiography to estimate stroke volumes while apnea with open glottis. We hypothesized that, when glottis is open, stroke volumes would be better estimated if airways flow curves were taken into account.

Effects of hypercapnia and hypocapnia on ventilatory variability and the chaotic dynamics of ventilatory flow in humans.

In humans, lung ventilation exhibits breath-to-breath variability and dynamics that are nonlinear, complex, sensitive to initial conditions, unpredictable in the long-term, and chaotic. Hypercapnia, as produced by the inhalation of a CO(2)-enriched gas mixture, stimulates ventilation. Hypocapnia, as produced by mechanical hyperventilation, depresses ventilation in animals and in humans during sleep, but it does not induce apnea in awake humans. This emphasizes the suprapontine influences on ventilatory control. How cortical and subcortical commands interfere thus depend on the prevailing CO(2) levels. However, CO(2) also influences the variability and complexity of ventilation. This study was designed to describe how this occurs and to test the hypothesis that CO(2) chemoreceptors are important determinants of ventilatory dynamics. Spontaneous ventilatory flow was recorded in eight healthy subjects. Breath-by-breath variability was studied through the coefficient of variation of several ventilatory variables. Chaos was assessed with the noise titration method (noise limit) and characterized with numerical indexes [largest Lyapunov exponent (LLE), sensitivity to initial conditions; Kolmogorov-Sinai entropy (KSE), unpredictability; and correlation dimension (CD), irregularity]. In all subjects, under all conditions, a positive noise limit confirmed chaos. Hypercapnia reduced breathing variability, increased LLE (P = 0.0338 vs. normocapnia; P = 0.0018 vs. hypocapnia), increased KSE, and slightly reduced CD. Hypocapnia increased variability, decreased LLE and KSE, and reduced CD. These results suggest that chemoreceptors exert a strong influence on ventilatory variability and complexity. However, complexity persists in the quasi-absence of automatic drive. Ventilatory variability and complexity could be determined by the interaction between the respiratory central pattern generator and suprapontine structures.

Respiratory inductive plethysmography to assess respiratory variability and complexity in humans.

Human ventilation is aperiodic, exhibiting a breath-by-breath variability and a complexity of which the characteristics may be interesting physiologically and clinically. In the present study, we tested the ability of respiratory inductive plethysmography (RIP) to describe these properties. Indeed, RIP does not have the effects on ventilation described with mouthpiece measurements. We compared the ventilatory flow recorded with a pneumotachograph (V'PNT) and the ventilatory flow derived from the mathematical treatment of the thoracoabdominal motion signals obtained from a particular type of RIP (V'RIP, Visuresp, Meylan, France) in 8 freely breathing normal subjects. Using the Z correlation coefficient, Passing-Bablock regressions and Bland and Altman graphical analyses, we compared the coefficients of variation of the main discrete respiratory variables determined with V'PNT and V'RIP and a set of nonlinear descriptors including the noise limit (chaotic nature of the signal), largest Lyapunov exponent (sensitivity to initial conditions), the Kolmogorov-Sinai entropy (unpredictability) and the correlation dimension (irregularity). When the recordings were obtained with the two techniques simultaneously, all the measurements were correlated and interchangeable. RIP can be safely used to quantify the breath-by-breath variability of ventilation and to study the complexity and the chaotic behavior of the ventilatory flow.

Use of computer and respiratory inductance plethysmography for the automated detection of swallowing in the elderly.

Deglutition disorders can occur at any age but are especially prevalent in the elderly. The resulting morbidity and mortality are being recognized as major geriatric health issues, Because of difficulties in studying swallowing in the frail elderly, a new, non-invasive, user-friendly, bedside technique has been developed. Ideally suited to such patients, this tool, an intermediary between purely instrumental and clinical methods, combines respiratory inductance plethysmography (RIP) and the computer to detect swallowing automatically, Based on an automated analysis of the airflow estimated by the RIP-derived signal, this new tool was evaluated according to its capacity to detect clinical swallowing from among the 1643 automatically detected respiratory events, This evaluation used contingency tables and Receiver Operator Characteristic (ROC) curves, Results were all significant (chi2(1,n=1643)>100, p<0.01). Considering its high accuracy in detecting swallowing (area under the ROC curve greater than 0.9), this system would be proposed to study deglutition and then deglutition disorders in the frail elderly, to set up medical supervision and to evaluate the efficiency of a swallowing disorder remedial therapeutic.

Evaluation of a device scoring classes of hemorrhagic shock.

In order to evaluate the feasibility of a device scoring classes of hemorrhagic shock, a multivariate analysis of physiological data collected on swine enduring continuous blood loss was conducted. Raw data sampled at up to 500 Hz were first preprocessed and used for features extraction over period of 1 mm. An expert scored all these physiological features, into one of the four classes of hemorrhagic shock: none, compensated, uncompensated and irreversible. A supervised learning of various classifiers was then evaluated over these data. The percentage of misclassification obtained when using a realistic way of estimating error (a leave one -animal- out validation) is about 20% when mean arterial pressure is used, and about 40% when only non invasive features are used. The results are about the same whatever the classifiers used. This evaluation is discussed and a visualization is proposed in order to assess the temporal supervision given by the classifiers.