Daniel Isabey - Academia.edu (original) (raw)

Papers by Daniel Isabey

Springer eBooks, 1990

Measurement of respiratory impedance by Forced Oscillations is an efficient method for characteri... more Measurement of respiratory impedance by Forced Oscillations is an efficient method for characterizing the mechanical behavior of the respiratory system [11, 12]. Recently, this method has been shown to enable early detection of airway abnormalities in subjects exposed to respiratory irritants [2]. The advantage of this non-invasive method is that it does not require cooperation from the patient, allowing him to breathe spontaneously through a connecting tube, usually flushed by a constant bias flow [2,11,15]. This is possible because the oscillating system is opened to the atmosphere by means of a hole or a side tube intended to be a low pass filter for the oscillations [12]. Surprisingly, the interaction between the quasi-steady component (spontaneous breathing and/or bias flow) and the oscillatory component of flow has rarely been considered from a fundamental point of view, except for two recent studies in laminar flow conditions [5,7]. However, a crucial problem remains for the case when the continuous component of flow becomes turbulent: then a linear phenomenon, i.e., the oscillatory flow component [12], is superimposed on a typically non-linear phenomenon, i.e., the turbulent component.

Springer eBooks, 1998

Changes in cells shape and function are due to the rearrangement of individual molecular componen... more Changes in cells shape and function are due to the rearrangement of individual molecular components that join together in space to form structural cytoskeletal frameworks [1]. Cells grow, survive, migrate, differentiate and remodel their architecture according to the physico-chemical processes which closely depend upon their mechanical environment [2]. However, the mechanotransduction phenomena and more generally mechanical properties of cells are yet poorly understood and it becomes of central interest to measure and analyze cells rheological behavior. Models of cytoskeletal networks and related cells mechanical responses have been recently proposed with, either, a physical viewpoint based upon the mechanics of continuous media [3, 4] or an analysis based upon the mechanics of discrete element structures. These recent models have taken into account the fact that the fibrous microscopic nature of the cytoskeletal components resembles the polymeric foam material [5] or have introduced the concept that living cells use tensegrity architecture for their organization [6]. The purpose of this study is to furthermore investigate these current modeling aspects with emphasis upon the structure mechanical approach: scale effect, anisotropy, non linearity of stress-strain relationships.

Irbm, Mar 1, 2015

Sudden death in ambulatory is a major public health issue: only few survivors, severe brain damag... more Sudden death in ambulatory is a major public health issue: only few survivors, severe brain damage, high socioeconomic cost. To improve survival and neurological recovery of these patients, an early therapeutic moderate hypothermia could be promising, as strongly suggested by previous preclinical studies on small animals through hypothermic total liquid ventilation (TLV) with perfluorocarbons (PFC) that maintain normal gas exchanges, and where lungs act as a heat exchanger (INSERM U955-E3, partner and pioneer of this project). Before translation of hypothermic TLV to humans, studies on large animals are necessary. The project ABYSS concerns the development and validation of a total liquid ventilator prototype suitable for large animals (no suitable devices exist on the market). ABYSS involves a consortium of 4 partners: an industrial company (Bertin Technologies) and three academic laboratories (INSERM U955-E3, INSERM U955-E13 and IR4M CNRS UMR8081). The study, which lasted three years, has led to: 1) Realize a prototype of total liquid ventilator for ventilating and cooling large animals, 2) Study the cooling on large animals with TLV, both on beating heart and under external cardiac massage, 3) Study another therapeutic indication: organ preservation of dead patients, 4) Compare three PFC already used as medical devices and analyze the impact of using PFCs with quite unusual physical properties on respiratory flows and airway resistance, 5) Study the miniaturization of the ventilator to enable its use in mobile intensive care unit. The next task will be to improve the understanding of the broncho-alveolar response (at various scales from organ to pulmonary cells) under total liquid ventilation on large animals, in order to get knowledge to improve and to optimize the tolerance of the respiratory system to liquid ventilation with PFC.

American Journal of Respiratory and Critical Care Medicine, 1994

A problem in mechanical ventilation is the accumulation of mucus secretions in the endotracheal t... more A problem in mechanical ventilation is the accumulation of mucus secretions in the endotracheal tube (ETT), which tends to reduce the patent cross-sectional area. Here we characterized the extent and locus of the ETT obstruction using an acoustic reflection method recently modified to be applied at bedside. Experiments were conducted both in vivo in 10 intubated patients and in vitro in ETT with or without known constrictions of 1 to 3 mm over 5 cm, located at various distances from the ETT entry: 5, 10, 15, and 20 cm. Acoustic results were compared with the results obtained by an hydraulic reference method, which was the only method available to measure ETT obstruction in mechanically ventilated patients. In vivo acoustic results showed that area reductions were maximal near the tracheal extremity of the ETT, with a range from 2 to 36% (mean value 13 +/- 10%), when estimated relative to the area measured in an unused ETT of the same inner diameter (7 to 9 mm). Statistical analysis of the differences between acoustic reflection data and hydraulic data showed that the two methods did not differ significantly. In vitro acoustic results obtained in constricted ETT showed a highly significant correlation with the actual area (r = 0.97, p = 0.0001). Thus, reductions in ETT area may be detected, quantified, and located by the present acoustic reflection method, which therefore provides a means to avoid emergency extubation because of ETT obstruction.

Bulletin of the American Physical Society, Nov 23, 2015

Systemic deterministic models of mucociliary clearance in the bronchial tree are currently scarce... more Systemic deterministic models of mucociliary clearance in the bronchial tree are currently scarce. While analytical/computational efforts have focused on microscopic modeling of mucociliary propulsion, macroscopic approaches have been restricted mainly to stochastic methods. We present an analytical/computational model that simulates mucociliary clearance in macroscopic physical domains. The analytical foundations of the model are based on a Stokes flow assumption, whereby, in addition to viscous forces originating in ciliary forcing, the role of surface tension is also considered. The governing equations are solved computationally on a three-dimensional surface mesh. Flow is simulated in an anatomically/geometrically representative bifurcation of the bronchial tree. The directionality of ciliary forcing in our model is optimized in order to maintain near-uniform mucus film thickness throughout the flow field. Based on the optimized version of the model, energetic considerations, as well as aspects of optimality in nature are analyzed and presented.

HAL (Le Centre pour la Communication Scientifique Directe), Jun 1, 2002

ABSTRACT We studied the relation between actin structural changes and cytoskeleton mechanical pro... more ABSTRACT We studied the relation between actin structural changes and cytoskeleton mechanical properties in living adherent epithelial alveolar cells, before and during actin depolymerization. The mechanical response of adherent alveolar epithelial cells was measured using magnetic twisting cytometry and a two-component model representing the cortical and the cytosolic elastic components at equilibrium. Chemiluminescent staining of the actin cytoskeleton was performed in the same living cells to estimate the intracellular actin density distribution for each cytoskeleton component. We found that (i) cytoskeleton alterations induced by actin depolymerization differed between the cortical and cytosolic cytoskeleton components (e.g., -30% and -49%, respectively, at a stress of 31 Pa) and that (ii) the concomitant change in actin distribution was also different (e.g., actin volume decrease was -7% and -19% for the cortical and cytosolic components, respectively).

$Research paper thumbnail of Flow Induced by \textit{Ex-Vivo} Nasal Cilia: Developing an Index of Dyskinesis$

Bulletin of the American Physical Society, Nov 20, 2017

Mucociliary clearance is one of the major lines of defense of the respiratory system. The mucus l... more Mucociliary clearance is one of the major lines of defense of the respiratory system. The mucus layer coating the pulmonary airways is moved along and out of the lung by the activity of motile cilia, thus expelling the particles trapped in it. Here we compare ex vivo measurements of a Newtonian flow induced by cilia beating (using micro-beads as tracers) and a mathematical model of this fluid flow. Samples of nasal epithelial cells placed in water are recorded by high-speed video-microscopy and ciliary beat pattern is inferred. Automatic tracking of micro-beads, used as markers of the flow generated by cilia motion, enables us also to assess the steady velocity profile as a function of the distance above the cilia. This profile is shown to be essentially parabolic. This compares well to a 2D mathematical model for ciliary fluid propulsion using an envelope model. From the model and the experimental measurements, the shear stress exerted by the cilia is deduced. Finally, this shear stress is proposed as a new index for characterizing the efficiency of ciliary beating and diagnosing dyskinesis.

CRC Press eBooks, Dec 26, 2000

Pressure support (PS) is characterized by a pressure plateau, which is usually generated at the v... more Pressure support (PS) is characterized by a pressure plateau, which is usually generated at the ventilator level (PS vent). We have built a PS device in which the pressure plateau can be obtained at the upper airway level (PS aw) or at the alveolar level (PS A). The effect of these different PS modes was evaluated in seven healthy men during air breathing and 5% CO 2 breathing. Minute ventilation during air breathing was higher with PS A than with PS aw and lower with PS vent (16 Ϯ 3, 14 Ϯ 3, and 11 Ϯ 2 l/min, respectively). By contrast, there were no significant differences in minute ventilation during 5% CO 2 breathing (25 Ϯ 5, 27 Ϯ 7, and 23 Ϯ 5 l/min, respectively). The esophageal pressure-time product per minute was lower with PS A than with PS aw and PS vent during air breathing (29 Ϯ 26, 44 Ϯ 44, and 48 Ϯ 30 cmH 2 O•s, respectively) and 5% CO 2 breathing (97 Ϯ 40, 145 Ϯ 62, and 220 Ϯ 41 cmH 2 O • s, respectively). In conclusion, during PS, moving the inspiratory pressure plateau from the ventilator to the alveolar level reduces pressure output, particularly at high ventilation levels.

Cilia, Jul 13, 2015

Ciliary dysfunctions may have deleterious consequences on mucociliary clearance. We propose a new... more Ciliary dysfunctions may have deleterious consequences on mucociliary clearance. We propose a new approach based on coupling the isolated ciliary beat pattern and the global efficiency of ciliary beat on human ciliated cells.

Clinical Otolaryngology, Jul 31, 2017

BioMed Research International, Dec 19, 2018

An excessive pulmonary inflammatory response could explain the poor prognosis of chronic obstruct... more An excessive pulmonary inflammatory response could explain the poor prognosis of chronic obstructive pulmonary disease (COPD) patients submitted to invasive mechanical ventilation. The aim of this study was to evaluate the response to normal tidal volume mechanical ventilation in an elastase-induced murine model of pulmonary emphysema. In this model, two time points, associated with different levels of lung inflammation but similar lung destruction, were analyzed. C57BL/6 mice received a tracheal instillation of 5 IU of porcine pancreatic elastase (Elastase mice) or the same volume of saline (Saline mice). Fourteen (D14) and 21 (D21) days after instillation, mice were anesthetized, intubated, and either mechanically ventilated (MV) or maintained on spontaneous ventilation (SV) during two hours. As compared with Saline mice, Elastase mice showed a similarly increased mean chord length and pulmonary compliance at D14 and D21, while bronchoalveolar lavage cellularity was comparable between groups. Lung mechanics was similarly altered during mechanical ventilation in Elastase and Saline mice. Activated alveolar macrophages CD11bmid were present in lung parenchyma in both Elastase SV mice and Elastase MV mice at D14 but were absent at D21 and in Saline mice, indicating an inflammatory state with elastase at D14 only. At D14, Elastase MV mice showed a significant increase in percentage of neutrophils in total lung, as compared with Elastase SV mice. Furthermore, alveolar macrophages of Elastase MV mice at D14 overexpressed Gr1, and monocytes showed a trend to overexpression of CD62L, compared with Elastase SV mice. In an elastase-induced model of pulmonary emphysema, normal tidal volume mechanical ventilation may produce an increase in the proportion of pulmonary neutrophils, and an activation of alveolar macrophages and pulmonary monocytes. This response seems to be observed only when the emphysema model shows an underlying inflammation (D14), reflected by the presence of activated alveolar macrophages CD11bmid.

HAL (Le Centre pour la Communication Scientifique Directe), Aug 1, 2002

Houille Blanche-revue Internationale De L Eau, 2005