Appropriate arterial function and structure are vital for a proper cardiovascular performance and therefore fundamental for a healthy life. Arterial function depends on cellular and molecular mechanisms but as well on the structural features. In fact, it has been shown that structural and biomechanical properties of vessels are very much related to several cardiovascular pathologies, such as systemic and pulmonary hypertension. Chronic lack of oxygen (hypoxia), may determine an impairment of the cardiovascular function, potentially deriving in pulmonary/systemic hypertension and cardiac failure. This is particularly relevant in human populations exposed to high altitude (above 2500m), either in chronic continuous (permanent inhabitants) or chronic intermittent (shifts of high altitude workers, such as miners, custom agents astronomers; and mountaineers) fashions. Most of the studies about vascular effects of chronic hypoxia have focused on function and molecular mechanisms involved in the pathophysiological responses. However, few is known about the biomechanical responses of systemic, pulmonary and cerebral arteries in these conditions, particularly in the chronic exposure to hypoxia as it happens in high-altitude population and in several diseases in lowlanders. The main goal of this project is to determine the vascular biomechanical characteristics of a representative rat paradigm of living under hypoxia and, in addition, establish the modelling, numerical simulation and experimental validation of the biomechanical responses of arterial vessels.
Specifically, three different types of vessels (aorta, carotid and femoral), at different age (neonates, juveniles and adults)
will be analyzed, either under normoxic, chronic permanent hypoxic or chronic intermittent hypoxic conditions.
Small rodents have been extensively used as a paradigm of cardiovascular and vascular function, allowing massive
steps in the knowledge of mechanisms involved in cardiovascular pathologies. Using a rat model, we will deeply analyze
the biomechanical properties of the vasculature of animals exposed to chronic hypoxia (permanent or intermittent) in a
hypobaric chamber, adding substantial data for the comprehension of the vascular biomechanical behaviour under these
conditions.
The need for a better understanding of the biomechanical response of arteries leads to the development of constitutive
models that may define realistic and reliable stress-strain relationships. In this project, several constitutive models aimed
at describing the biomechanical behaviour of soft tissues will be assessed. The specific aspects to be taken into account
of the vessels biomechanical characterisation are: incompressibility of the tissue, presence of large deformations, isotropic and anisotropic material behaviours, residual stresses, rate dependent (i.e., viscous) effects, damage and active response. The material characterisation of the biomechanical behaviour of rat arteries will be performed via in-vitro biaxial and myograph tensile tests and ring opening test, considering standard, cyclic and relaxation loading conditions. From these experiments, the material characterisation will also involve the derivation of the material parameters. Specifically, we will address the development of algorithms for the treatment of non-linearities in the fitting procedure and sensitivity analysis to determine the consistency of the parameters found with this methodology. The analysis will also include comparison between the numerical predictions of the different constitutive models in their application to experimental data to be measured in this project.
The analysis of the response of pressurised straight arterial vessels will be additionally carried out. Importantly, this
test mimics the in-vivo physiological conditions of the arterial vessel. Aside from the internal pressure, axial stretching is
usually considered. As a non-uniform biaxial stress state is commonly developed in this test, this fact extends the validity of the material characterisation. The material response will be described via the constitutive models previously characterised. Due to the complex stress and strain patterns developed in this problem, numerical simulations defined in the context of the finite element method will be performed. The obtained numerical results will be validated with the corresponding experimental measurements. Moreover, we expect to characterise the biomechanical properties of different vascular beds, representatives of systemic, pulmonary and cerebral circulations. We shall also describe the effects of chronic hypoxia on these properties. Furthermore, we will perform histological analyses to assess the ultrastructure and the wall components of the intima, media and adventitia layers and relate them with the biomechanical findings.
The outcomes of this project will enhance the knowledge necessary to integrate the functional, structural and
biomechanical properties of vascular tissues. Clearly, our data will provide useful information not only for vascular pathophysiology understanding, but also for optimization of medical diagnosis, prognosis and potential therapeutic approaches to the related pathologies