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Biomedical subjects

M Filoche

Publications and source records attributed to M Filoche.

9 recordsLinked to original sources
PubMed2004

An optimal bronchial tree may be dangerous.

The geometry and dimensions of branched structures such as blood vessels or airways are important factors in determining the efficiency of physiological processes. It has been shown that fractal trees can be space filling and can ensure minimal dissipation. The bronchial tree of most mammalian lungs is a good example of an efficient distribution system with an approximate fractal structure. Here we present a study of the compatibility between physical optimization and physiological robustness in the design of the human bronchial tree. We show that this physical optimization is critical in the sense that small variations in the geometry can induce very large variations in the net air flux. Maximum physical efficiency therefore cannot be a sufficient criterion for the physiological design of bronchial trees. Rather, the design of bronchial trees must be provided with a safety factor and the capacity for regulating airway calibre. Paradoxically, our results suggest that bronchial malfunction related to asthma is a necessary consequence of the optimized efficiency of the tree structure.

Asthma↗
PubMed2004

Renormalized random walk study of oxygen absorption in the human lung.

The possibility to renormalize random walks is used to study numerically the oxygen diffusion and permeation in the acinus, the diffusion cell terminating the mammalian airway tree. This is done in a 3D tree structure which can be studied from its topology only. The method is applied to the human acinus real morphology as studied by Haefeli-Bleuer and Weibel in order to compute the respiratory efficiency of the human lung. It provides the first quantitative evidence of the role of diffusion screening in real 3D mammalian respiration. The net result of this study is that, at rest, the efficiency of the human acinus is only of order 33%. Application of these results to CO2 clearance provides for the first time a theoretical support to the empirical relation between the O2 and CO2 partial pressures in blood.

Bronchi↗
PubMed2003

Interplay between geometry and flow distribution in an airway tree.

Uniform flow distribution in a symmetric volume can be realized through a symmetric branched tree. It is shown here, however, by 3D numerical simulation of the Navier-Stokes equations, that the flow partitioning can be highly sensitive to deviations from exact symmetry if inertial effects are present. The flow asymmetry is quantified and found to depend on the Reynolds number. Moreover, for a given Reynolds number, we show that the flow distribution depends on the aspect ratio of the branching elements as well as their angular arrangement. Our results indicate that physiological variability should be severely restricted in order to ensure adequate fluid distribution through a tree.

Animals↗
PubMed2003

Diffusional screening in the human pulmonary acinus.

In the mammalian lung acini, O(2) diffuses into quasi-static air toward the alveolar membrane, where the gas exchange with blood takes place. The O(2) flux is then influenced by the O(2) diffusivity, the membrane permeability, and the acinus geometric complexity. This phenomenon has been recently studied in an abstract geometric model of the acinus, the Hilbert acinus (Sapoval B, Filoche M, and Weibel ER, Proc Natl Acad Sci USA 99: 10411, 2002). This is extended here to a more realistic geometry originated from the morphological model of Kitaoka et al. (Kitaoka K, Tamura S, and Takaki R, J Appl Physiol 88: 2260-2268, 2000). Two-dimensional numerical simulations of the steady-state diffusion equation with mixed boundary conditions are used to quantify the process. The alveolar O(2) concentration, or partial pressure, and the O(2) flux are computed and show that diffusional screening exists at rest. These results confirm that smaller acini are more efficient, as suggested for the Hilbert acini.

Algorithms↗
PubMed2002

Smaller is better--but not too small: a physical scale for the design of the mammalian pulmonary acinus.

The transfer of oxygen from air to blood in the lung involves three processes: ventilation through the airways, diffusion of oxygen in the air phase to the alveolar surface, and finally diffusion through tissue into the capillary blood. The latter two steps occur in the acinus, where the alveolar gas-exchange surface is arranged along the last few generations of airway branching. For the acinus to work efficiently, oxygen must reach the last branches of acinar airways, even though some of it is absorbed along the way. This "screening effect" is governed by the relative values of physical factors like diffusivity and permeability as well as size and design of the acinus. Physics predicts that efficient acini should be space-filling surfaces and should not be too large. It is shown that the mammalian acini fulfill these requirements, small mammals being more efficient than large ones both at rest and in exercise.

Animals↗
PubMed2000

Diffusion-reorganized aggregates: attractors in diffusion processes?

A process based on particle evaporation, diffusion, and redeposition is applied iteratively to a two-dimensional object of arbitrary shape. The evolution spontaneously transforms the object morphology, converging to branched structures. Independently of initial geometry, the structures found after a long time present fractal geometry with a fractal dimension around 1.75. The final morphology, which constantly evolves in time, can be considered as the dynamic attractor of this evaporation-diffusion-redeposition operator. The ensemble of these fractal shapes can be considered to be the dynamical equilibrium geometry of a diffusion-controlled self-transformation process.

Journal Article↗
PubMed2000

Transfer across random versus deterministic fractal interfaces.

A numerical study of the transfer across random fractal surfaces shows that their responses are very close to the response of deterministic model geometries with the same fractal dimension. The simulations of several interfaces with prefractal geometries show that, within very good approximation, the flux depends only on a few characteristic features of the interface geometry: the lower and higher cutoffs and the fractal dimension. Although the active zones are different for different geometries, the electrode responses are very nearly the same. In that sense, the fractal dimension is the essential "universal" exponent which determines the net transfer.

Journal Article↗
PubMed2000

A unified theory of the B-Z transition of DNA in high and low concentrations of multivalent ions.

We showed recently that the high-salt transition of poly[d(G-C)]. poly[d(G-C)] between B-DNA and Z-DNA (at [NaCl] = 2.25 M or [MgCl(2)] = 0.7 M) can be ascribed to the lesser electrostatic free energy of the B form, due to better immersion of the phosphates in the solution. This property was incorporated in cylindrical DNA models that were analyzed by Poisson-Boltzmann theory. The results are insensitive to details of the models, and in fair agreement with experiment. In contrast, the Z form of the poly[d(G-m5C)] duplex is stabilized by very small concentrations of magnesium. We now show that this striking difference is accommodated quantitatively by the same electrostatic theory, without any adjustable parameter. The different responses to magnesium of the methylated and nonmethylated polymers do not come from stereospecific cation-DNA interactions: they stem from an experimentally derived, modest difference in the nonelectrostatic component of the free energy difference (or NFED) between the Z and B forms. The NFED is derived from circular DNA measurements. The differences between alkaline earth and transition metal ions are explained by weak coordination of the latter. The theory also explains the induction of the transition by micromolar concentrations of cobalt hexammine, again without specific binding or adjustable parameters. Hence, in the case of the B-Z transition as in others (e.g., the folding of tRNA and of ribozymes), the effect of multivalent cations on nucleic acid structure is mediated primarily by nonspecific ion-polyelectrolyte interactions. We propose this as a general rule for which convincing counter-examples are lacking.

Circular Dichroism↗