Modeling essential hypertension with a closed-loop mathematical model for the entire human circulation.

Arterial hypertension, defined as an increase in systemic arterial pressure, is a major risk factor for the development of diseases affecting the cardiovascular system. Every year, 9.4 million deaths worldwide are caused by complications arising from hypertension. Despite well-established approaches to diagnosis and treatment, fewer than half of all hypertensive patients have adequately controlled blood pressure. In this scenario, computational models of hypertension can be a practical approach for better quantifying the role played by different components of the cardiovascular system in the determination of this condition. In the present work we adopt a global closed-loop multi-scale mathematical model for the entire human circulation to reproduce a hypertensive scenario. In particular, we modify the model to reproduce alterations in the cardiovascular system that are cause and/or consequence of the hypertensive state. The adaptation does not only affect large systemic arteries and the heart but also the microcirculation, the pulmonary circulation and the venous system. Model outputs for the hypertensive scenario are validated through assessment of computational results against current knowledge on the impact of hypertension on the cardiovascular system.

Cerebrospinal fluid dynamics coupled to the global circulation in holistic setting: Mathematical models, numerical methods and applications.

This paper presents a mathematical model of the global, arterio-venous circulation in the entire human body, coupled to a refined description of the cerebrospinal fluid (CSF) dynamics in the craniospinal cavity. The present model represents a substantially revised version of the original Müller-Toro mathematical model. It includes one-dimensional (1D), non-linear systems of partial differential equations for 323 major blood vessels and 85 zero-dimensional, differential-algebraic systems for the remaining components. Highlights include the myogenic mechanism of cerebral blood regulation; refined vasculature for the inner ear, the brainstem and the cerebellum; and viscoelastic, rather than purely elastic, models for all blood vessels, arterial and venous. The derived 1D parabolic systems of partial differential equations for all major vessels are approximated by hyperbolic systems with stiff source terms following a relaxation approach. A major novelty of this paper is the coupling of the circulation, as described, to a refined description of the CSF dynamics in the craniospinal cavity, following Linninger et al. The numerical solution methodology employed to approximate the hyperbolic non-linear systems of partial differential equations with stiff source terms is based on the Arbitrary DERivative Riemann problem finite volume framework, supplemented with a well-balanced formulation, and a local time stepping procedure. The full model is validated through comparison of computational results against published data and bespoke MRI measurements. Then we present two medical applications: (i) transverse sinus stenoses and their relation to Idiopathic Intracranial Hypertension; and (ii) extra-cranial venous strictures and their impact in the inner ear circulation, and its implications for Ménière's disease.