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Biomedical subjects

D Ambrosi

Publications and source records attributed to D Ambrosi.

16 recordsLinked to original sources

Mechanics and chemotaxis in the morphogenesis of vascular networks.

The formation of vascular networks in vitro develops along two rather distinct stages: during the early migration-dominated stage the main features of the pattern emerge, later the mechanical interaction of the cells with the substratum stretches the network. Mathematical models in the relevant literature have been focusing just on either of the aspects of this complex system. In this paper, a unified view of the morphogenetic process is provided in terms of physical mechanisms and mathematical modeling.

Algorithms↗

Cell directional persistence [corrected] and chemotaxis in vascular morphogenesis.

In vertebrates, supply of oxygen and nutrients to tissues is carried out by the blood vascular system through capillary networks. Capillary patterns are closely mimicked by endothelial cells cultured on Matrigel, a preparation of basement membrane proteins. On the Matrigel surface, single randomly dispersed endothelial cells self-organize into vascular networks. The network is characterized by a typical length scale, which is independent of the initial mean density of deposed cells n over a wide range of values of n. We give here a detailed description of a mathematical model of the process which is able to reproduce several qualitative and quantitative features of in vitro vascularization experiments. Cell matter is basically modelled as an elastic fluid subjected to a specific force field depending on the concentration of a chemoattractant factor. Starting from sparse initial data, mimicking the initial conditions realized in laboratory experiments, numerical solutions reproduce characteristic network structures, similar to observed ones, whose average size is theoretically related to the finite range of chemoattractant diffusion. A possible area of application of the model is the design of properly vascularized artificial tissues.

Blood Vessels↗

The role of stress in the growth of a multicell spheroid.

Rather recent experimental results demonstrate the non-negligible role of mechanical stress in the growth of a multicell spheroid. In this paper we discuss a theoretical framework for volumetric growth suitable for modeling the growth of soft tissues exhibiting the properties of a solid. After a proper kinematic decomposition, balance equations for mass, momentum and energy are discussed together with constitutive relationships. The mathematical model is then applied to avascular tumor growth. We show by numerical simulation that, under assumption of spherical symmetry, the mathematical model is able to reproduce the experimental data with a satisfying qualitative agreement.

Algorithms↗

Percolation, morphogenesis, and burgers dynamics in blood vessels formation.

Experiments of in vitro formation of blood vessels show that cells randomly spread on a gel matrix autonomously organize to form a connected vascular network. We propose a simple model which reproduces many features of the biological system. We show that both the model and the real system exhibit a fractal behavior at small scales, due to the process of migration and dynamical aggregation, followed at large scale by a random percolation behavior due to the coalescence of aggregates. The results are in good agreement with the analysis performed on the experimental data.

Computer Simulation↗

A hybrid (numerical-physical) model of the left ventricle.

Hydraulic models of the circulation are used to test mechanical devices and for training and research purposes; when compared to numerical models, however, they are not flexible enough and rather expensive. The solution proposed here is to merge the characteristics and the flexibility of numerical models with the functions of physical models. The result is a hybrid model with numerical and physical sections connected by an electro-hydraulic interface - which is to some extent the main problem since the numerical model can be easily changed or modified. The concept of hybrid model is applied to the representation of ventricular function by a variable elastance numerical model. This prototype is an open loop circuit and the physical section is built out of a reservoir (atrium) and a modified windkessel (arterial tree). The corresponding equations are solved numerically using the variables (atrial and arterial pressures) coming from the physical circuit. Ventricular output flow is the computed variable and is sent to a servo amplifier connected to a DC motor-gear pump system. The gear pump, behaving roughly as a flow source, is the interface to the physical circuit. Results obtained under different hemodynamic conditions demonstrate the behaviour of the ventricular model on the pressure-volume plane and the time course of output flow and arterial pressure.

Heart Ventricles↗

A physical model of the human systemic arterial tree.

A physical model of the human arterial tree has been developed to be used in a computer controlled mock circulatory system (MCS). Its aim is to represent systemic arterial tree properties and extend the capacity of the MCS to intraortic balloon pump (IABP) testing. The main problem was to model the aorta simply and to accurately reproduce aortic impedance and related flow and pressure waveforms at different sections. The model is composed of eight segments; lumped parameter models are used for its peripheral loads. After the numerical simulation, the physical model was reproduced as a silicon rubber tapered tube. This rubber was chosen for its stability over time and the acceptable behaviour of its Young's modulus (Ey = 22.23 gf x mm(-2)) with different loads and in comparison with data from the literature (Ey approximately 20.4 gf x mm(-2)). The properties of each segment of the aorta were defined in terms of compliance, resistance and inertance as a function of length, radius and thickness. The variable thickness was obtained using positive and negative molds. Total static compliance of the aorta model is about 1.125 x 10(-3) g(-1) x cm4 x sec2 (1.5 cm3 x mmHg(-1)). Measurements were performed both on numerical and physical models (in open and closed loop configuration). Data reported show pressure and flow waveforms along with input impedance modulus and phase. The results are in good agreement with data from the literature.

Aorta↗

A computer controlled mock circulatory system for mono- and biventricular assist device testing.

The clinical use of heart assist devices for heart recovery, implies the problem of their in vitro testing and training to use. In a mock circulatory system developed to this aim, the main problem is reproducing interaction among the device, the ventricle and the circulatory network. This can be analysed by the position, on the p-v plane, of the working point defined by the intersection between end systolic ventricular (ESPVR) and arterial elastance lines. The system developed on this basis, connectable to mono- and biventricular parallel assist devices, was a closed loop model including systemic and pulmonary circulation. The arterial trees were reproduced by two windkessels with adjustable peripheral resistance, and the Starling's law of the heart by a variable elastance model. The software controls and monitors circulatory parameters and variables. Results showed the behavior of the system with preload or afterload changes. Further, the reproduction of physiological, pathological (obtained by modifying slope and volume intercept of the ESPVR line) and LVAD assisted circulatory conditions was shown. The assistance effect was underlined by the changes in the ventricular work cycle and in hemodynamics variables. The evaluation of the effect of device control strategy on the ventricle and its energetics (on p-v plane) were among the main characteristics of this system, which ought to be further improved to test devices such as the IABP, which requires a different aortic model.

Blood Pressure↗

In vitro testing of a left ventricular assist device. Study of the effect of its control strategy on energetic relationships inside the left ventricle.

In this study an original left ventricular assist device is tested on an open loop modular physical circuit reproducing Starling's law of the heart to set an optimal control strategy for heart recovery. It is assumed that the goals of the assistance are reduction of oxygen consumption, external work and improvement of cardiac mechanical efficiency. The assistance is evaluated by the position of a working point on the characteristic surfaces of the ventricle defined by peripheral resistance, atrial pressure and selected variables pertaining to energy (pressure-volume area, external work and cardiac mechanical efficiency). In this frame an optimal assistance for heart recovery is a compromise among different requirements corresponding to a restricted set of control parameters values: driving pressure PZB = 35 kPa and timing values T1 and T2 (systole beginning and systole ending in relation to QRS complex and cardiac cycle duration T) T1 = 0.55.T and T2 = 0.73.T.

Bioelectric Energy Sources↗

A desk-top computer model of the circulatory system for heart assistance simulation: effect of an LVAD on energetic relationships inside the left ventricle.

The study of the interaction between a pneumatic left ventricle assist device (LVAD), driven with different control strategies, and the cardiovascular system is the subject of this paper. It is performed by a modular numerical model of the cardiovascular system connected to a numerical model of the LVAD. The circulatory system is simulated by a lumped parameter numerical model. The ventricle is represented by a time-varying elastance model to reproduce the Starling law of the heart. The effect of the LVAD on the cardiovascular system is evaluated, on the left ventricle alone, by an open-loop circuit consisting of the models of the ventricle, the LVAD and the arterial tree. The analysis is performed in terms of energy variables (such as external work and oxygen consumption and cardiac mechanical efficiency versus control strategy. The LVAD is driven by different control strategies: a fixed heart rate (with different delays from the onset of the natural ventricle contraction) and a variable heart rate.

Cardiovascular Physiological Phenomena↗

A modular numerical model of the cardiovascular system for studying and training in the field of cardiovascular physiopathology.

A modular numerical model of the cardiovascular system has been developed to reproduce the most important circulatory phenomena in terms of pressure and volume relationships. It is an easy tool to use, designed to be used with a friendly approach on any IBM or compatible personal computer: it offers a wide selection of graphical and numerical outputs and can be rearranged easily for a particular experiment. A set of subroutines related to different circulatory phenomena has been developed; they can be assembled easily together and communicate with each other by two variables. A full description of the existing subroutines is presented in this paper with three different application examples resulting from the rearrangement of the existing software modules: the first concerns the behaviour of the natural ventricle model itself and can be regarded as a ventricle stand-alone characterization test in terms of preload and afterload sensitivities, the second is related to the use of a pneumatic ventricle instead of the model of the natural ventricle, and the third is a full model of the cardiocirculatory system.

Cardiology↗

Effect of magnetic fluids on the efficiency of an electromagnetic actuator prototype.

An electromagnetic actuator to substitute ventricular function presents some advantages compared with different energy converters. The drastic reduction of the moving parts leads to greater reliability and an accurate control system can be set up. Its major limitations concern weight, heat dissipation and, finally, the overall pump efficiency which is usually rather low. We investigated the possibility of using magnetic fluids in an electromagnetic actuator. Limitations intrinsic to the magnetic fluids prevent their being used as pumping elements but they can be useful to increase the pump efficiency by reducing losses in the magnetic circuit. A remarkable increase in pump efficiency was attained. It is necessary to point out that in designing the electromagnetic actuator the focus was on the pump efficiency with and without the magnetic fluids more than on its performance.

Electromagnetic Phenomena↗

Mock circulatory system for in vitro reproduction of the left ventricle, the arterial tree and their interaction with a left ventricular assist device.

A modular physical circuit for testing monoventricular and biventricular heart assist devices (HAD) is under development. The modules now available are assembled in an open-loop circuit and reproduce the function of the left ventricle and the systemic arterial tree. The left ventricle model reproduces Starling's law of the heart and can be easily controlled to modify other parameters such as contractility and timing (i.e. heart rate and systole/diastole ratio). This circuit, in connection with a left ventricular assist device (LVAD), can be used to evaluate the LVAD performance, its effect on the circulatory system and as a training system. This paper is devoted to a description of the circuit and of its interaction with a LVAD, which is analysed after the simulation of a low contractility pathology of the ventricle. Results obtained in these experiments are reported.

Heart-Assist Devices↗