Neuroprotective effects of xenon: a therapeutic window of opportunity in rats subjected to transient cerebral ischemia.

Brain insults are a major cause of acute mortality and chronic morbidity. Given the largely ineffective current therapeutic strategies, the development of new and efficient therapeutic interventions is clearly needed. A series of previous investigations has shown that the noble and anesthetic gas xenon, which has low-affinity antagonistic properties at the N-methyl-D-aspartate (NMDA) receptor, also exhibits potentially neuroprotective properties with no proven adverse side effects. Surprisingly and in contrast with most drugs that are being developed as therapeutic agents, the dose-response neuroprotective effect of xenon has been poorly studied, although this effect could be of major critical importance for its clinical development as a neuroprotectant. Here we show, using ex vivo and in vivo models of excitotoxic insults and transient brain ischemia, that xenon, administered at subanesthetic doses, offers global neuroprotection from reduction of neurotransmitter release induced by ischemia, a critical event known to be involved in excitotoxicity, to reduction of subsequent cell injury and neuronal death. Maximal neuroprotection was obtained with xenon at 50 vol%, a concentration at which xenon further exhibited significant neuroprotective effects in vivo even when administered up to 4 h after intrastriatal NMDA injection and up to at least 2 h after induction of transient brain ischemia.

In vitro validation of computational fluid dynamic simulation in human proximal airways with hyperpolarized 3He magnetic resonance phase-contrast velocimetry.

Computational fluid dynamics (CFD) and magnetic resonance (MR) gas velocimetry were concurrently performed to study airflow in the same model of human proximal airways. Realistic in vivo-based human airway geometry was segmented from thoracic computed tomography. The three-dimensional numerical description of the airways was used for both generation of a physical airway model using rapid prototyping and mesh generation for CFD simulations. Steady laminar inspiratory experiments (Reynolds number Re = 770) were performed and velocity maps down to the fourth airway generation were extracted from a new velocity mapping technique based on MR velocimetry using hyperpolarized (3)He gas. Full two-dimensional maps of the velocity vector were measured within a few seconds. Numerical simulations were carried out with the experimental flow conditions, and the two sets of data were compared between the two modalities. Flow distributions agreed within 3%. Main and secondary flow velocity intensities were similar, as were velocity convective patterns. This work demonstrates that experimental and numerical gas velocity data can be obtained and compared in the same complex airway geometry. Experiments validated the simulation platform that integrates patient-specific airway reconstruction process from in vivo thoracic scans and velocity field calculation with CFD, hence allowing the results of this numerical tool to be used with confidence in potential clinical applications for lung characterization. Finally, this combined numerical and experimental approach of flow assessment in realistic in vivo-based human airway geometries confirmed the strong dependence of airway flow patterns on local and global geometrical factors, which could contribute to gas mixing.

Inspiratory flow in the nose: a model coupling flow and vasoerectile tissue distensibility.

We have developed a discrete multisegmental model describing the coupling between inspiratory flow and nasal wall distensibility. This model is composed of 14 individualized compliant elements, each with its own relationship between cross-sectional area and transmural pressure. Conceptually, this model is based on flow limitation induced by the narrowing of duct due to collapsing pressure. For a given inspiratory pressure and for a given compliance distribution, this model predicts the area profile and inspiratory flow. Acoustic rhinometry and posterior rhinomanometry were used to determine the initial geometric area and mechanical characteristics of each element. The proposed model, used under steady-state conditions, is able to simulate the pressure-flow relationship observed in vivo under normal conditions (4 subjects) and under pathological conditions (4 vasomotor rhinitis and 3 valve syndrome subjects). Our results suggest that nasal wall compliance is an essential parameter to understand the nasal inspiratory flow limitation phenomenon and the associated increase of resistance that is well known to physiologists. By predicting the functional pressure-flow relationship, this model could be a useful tool for the clinician to evaluate the potential effects of treatments.

Airflow modeling of steady inspiration in two realistic proximal airway trees reconstructed from human thoracic tomodensitometric images.

Detailed description of the flow field in human airways is highly important to better understand human breathing and provide a patient's customized diagnosis. An integrated numerical simulation platform is presently proposed in order to incorporate medical images into a numerical software to calculate flow field and to analyze it in terms of fluid dynamics. The platform was set up to compute steady inspiratory airflow in realistic human airways reconstructed from tomodensitometric medical images at resting breathing conditions. This morpho-functional simulation platform has been tested retrospectively with two CT-scanned patient airway morphological models: (i) a normal airway model (subject A) with no evidence of morphological alteration and (ii) a highly altered airway model (subject B) exhibiting a severe stenosis in the right main bronchus. First, various morphological aspects proper to each airway model are provided to show the performance and interest of the reconstruction method. Second, we describe the three-dimensional flow patterns associated to the global morphological features, which are mainly shared by the present realistic models and previous idealistic airway models. Finally, the flow characteristics associated to local morphological features specific to realistic airway models are discussed. The results demonstrate that the morpho-functional simulation platform is able to capture the main features of airway velocity patterns but also more specific airflow patterns which are related to customized patient morphological features such as laminar vortex formation. The present results suggest that the proposed airway functional imaging platform is adequate to provide most of functional information related to airflow and enable a patient to patient diagnosis.

Simulation of the regional manifestation of asthma.

Asthma presents serious medical problems of global proportions. Clinical data suggest that the disease occurs preferentially at regions designated by large (0

Frictional resistance sheds light on the multicomponent nature of nasal obstruction: a combined in vivo and computational fluid dynamics study.

Exploring nasal flow contributes to better understanding of pathophysiological functions of nasal cavities. We combined the rhinomanometry measurements of 11 patients and computational fluid dynamics (CFD) simulations in 3 nasal airway models to dissect the complex mechanisms that determine nasal flow obstruction: spatial complexity and pressure-dependent deformability of nasal airways. We quantified spatial complexity by calculating longitudinal variations of hydraulic diameter, perimeter and area of nasal cavities, and their impact on flow characteristics by examining the longitudinal variations of the kinetic energy coefficient and the kinetic to potential energy ratio. Airway distensibility variably affected in vivo pressure-flow relationships through the appearance of flow-limitation patterns characterized by maximum flow and/or flow plateau. We quantified deformability and spatial complexity effects on nasal airway resistance by normalizing all data with averaged reference parameters. The results show that discrepancies in nasal flow resistances reflect airway deformability and geometrical complexity, and thereby constitute a framework to better characterize nasal obstruction.

Phase-contrast velocimetry with hyperpolarized 3He for in vitro and in vivo characterization of airflow.

This paper describes a technique that combines radial MRI and phase contrast (PC) to map the velocities of hyperpolarized gases ((3)He) in respiratory airways. The method was evaluated on well known geometries (straight and U-shaped pipes) before it was applied in vivo. Dynamic 2D maps of the three velocity components were obtained from a 10-mm slice with an in-plane spatial resolution of 1.6 mm within 1 s. Integration of the in vitro through-plane velocity over the slice matched the input flow within a relative precision of 6.4%. As expected for the given Reynolds number, a parabolic velocity profile was obtained in the straight pipe. In the U-shaped pipe the three velocity components were measured and compared to a fluid-dynamics simulation so the precision was evaluated as fine as 0.025 m s(-1). The technique also demonstrated its ability to visualize vortices and localize characteristic points, such as the maximum velocity and vortex-center positions. Finally, in vivo feasibility was demonstrated in the human trachea during inhalation.

In vitro experiments and numerical simulations of airflow in realistic nasal airway geometry.

Pressure-flow relationships measured in human plastinated specimen of both nasal cavities and maxillary sinuses were compared to those obtained by numerical airflow simulations in a numerical three-dimensional reconstruction issued from CT scans of the plastinated specimen. For experiments, flow rates up to 1,500 ml/s were tested using three different gases: HeO(2), Air, and SF(6). Numerical inspiratory airflow simulations were performed for flow rates up to 353 ml/s in both the nostrils using a finite-volume-based method under steady-state conditions with CFD software using a laminar model. The good agreement between measured and numerically computed total pressure drops observed up to a flow rate of 250 ml/s is an important step to validate the ability of CFD software to describe flow in a physiologically realistic binasal model. The major total pressure drop was localized in the nasal valve region. Airflow was found to be predominant in the inferior median part of nasal cavities. Two main vortices were observed downstream from the nasal valve and toward the olfactory region. In the future, CFD software will be a useful tool for the clinician by providing a better understanding of the complexity of three-dimensional breathing flow in the nasal cavities allowing more appropriate management of the patient's symptoms.