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In recent years, several works have addressed the problem of modeling blood flow phenomena in veins, as a response to increasing interest in modeling pathological conditions occurring in the venous network and their connection with the rest of the circulatory system. In this context, one-dimensional models have proven to be extremely efficient in delivering predictions in agreement with in-vivo observations. Pursuing the increase of anatomical accuracy and its connection to physiological principles in haemodynamics simulations, the main aim of this work is to describe a novel closed-loop Anatomically-Detailed Arterial-Venous Network (ADAVN) model. An extremely refined description of the arterial network consisting of 2,185 arterial vessels is coupled to a novel venous network featuring high level of anatomical detail in cerebral and coronary vascular territories. The entire venous network comprises 189 venous vessels, 79 of which drain the brain and 14 are coronary veins. Fundamental physiological mechanisms accounting for the interaction of brain blood flow with the cerebro-spinal fluid and of the coronary circulation with the cardiac mechanics are considered. Several issues related to the coupling of arterial and venous vessels at the microcirculation level are discussed in detail. Numerical simulations are compared to patient records published in the literature to show the descriptive capabilities of the model. Furthermore, a local sensitivity analysis is performed, evidencing the high impact of the venous circulation on main cardiovascular variables.

There is increasing interest in understanding the physiology of the extracellular fluid compartments in the central nervous system and their dynamic interaction. Such interest has been in part prompted by a vigorous resurgence of the role of the venous system, the recent discoveries of the meningeal lymphatics, the brain waste removal mechanisms and their potential link to neurological diseases, such as idiopathic intracranial hypertension, Ménière’s disease, migraine, small vessel disease, and most neurodegenerative diseases. The rigid cranial cavity houses several space-competing material compartments: the brain parenchyma (BP) and four extracellular fluids, namely arterial, venous, cerebrospinal fluid (CSF) and interstitial fluid (ISF). During cardiac pulsations, the harmonious, temporal and spatial dynamic interaction of all these fluid compartments and the BP assures a constant intracranial volume at all times, consistent with the Monro-Kellie hypothesis. The dynamic interaction involves high-pressure input of arterial blood during systole and efflux of CSF into the spinal subarachnoid space (SSAS) followed by venous blood exiting directly into the vertebral and internal jugular veins towards the heart and intraventricular CSF displacing caudally towards the SSAS. Arterial pulsatile energy is transmitted to the BP that contributes to the smooth movement of fluids in and out of the brain. Perturbing any of these fluid compartments will alter the entire brain dynamics, potentially increase intracranial pressure, affect perfusion and hamper clearance capacity of metabolic waste. This review of all major extracellular fluid compartments within the brain, advocates a holistic approach to our understanding of the fluid dynamics, rather than focusing on a single compartment when analyzing neurological diseases. This approach may contribute to advance our comprehension of some common neurological disorders, paving the way to newer treatment options.

Ménière’s disease (MD) is a pathology of the inner ear, the symptoms of which include tinnitus, vertigo attacks, fluctuating hearing loss, and nausea. Neither cause nor cure are currently known, though animal experiments suggest that disruption of the inner ear circulation, including venous hypertension and endolymphatic hydrops, to be hallmarks of the disease. Recent evidence for humans suggests a potential link to strictures in the extracranial venous outflow routes. The purpose of the present work is to demonstrate that the inner-ear circulation in humans is disrupted by extracranial venous outflow stricture and to discuss the implications of this finding for MD. The hypothesis linking extracranial venous outflow strictures to the altered dynamics of central nervous system (CNS) fluid compartments is investigated theoretically via a global, closed-loop, multiscale mathematical model for the entire human circulation, interacting with the brain parenchyma and cerebrospinal fluid (CSF). The fluid dynamics model for the full human body includes submodels for the heart, pulmonary circulation, arterial system, microvasculature, venous system and the CSF, with a specially refined description of the inner ear vasculature. We demonstrate that extracranial venous outflow strictures disrupt inner ear circulation, and more generally, alter the dynamics of fluid compartments in the whole CNS. Specifically, as compared to a healthy control, the computational results from our model show that subjects with extracranial outflow venous strictures exhibit: altered inner ear circulation, redirection of flow to collaterals, increased intracranial venous pressure and increased intracranial pressure. Our findings are consistent with recent clinical evidence in humans that links extracranial outflow venous strictures to MD, aid the mechanistic understanding of the underlying features of the disease and lend support to recently proposed biophysically motivated therapies aimed at reducing the overall pressure in the inner ear circulation. More work is required to understand the finer details of the condition, such as the associated dynamics of fluids in the perilymphatic and endolymphatic spaces, so as to incorporate such knowledge into the mathematical models in order to reflect the real physiology more closely.

Cell oxygenation and nutrition is vitally important for human and animal life. Oxygen and nutrients are transported by the blood stream and cross microvessel walls to penetrate the cell’s membrane. Pathological alterations in the transport of oxygen, and other nutrition elements, across microvessel walls may have serious consequences to cell life, possibly leading to localized cell necrosis. We present a transient model of plasma filtration and solute transport across microvessel walls by coupling flow and transport equations, the latter being non-linear in solute concentration. The microvessel wall is modeled through the superimposition of two or more membranes with different physical properties, representing key structural elements. With this model, the combined effect of the endothelial cells, the glycocalyx and other coating membranes specific of certain microvessels, can be analyzed. We investigate the role of transient external pressures in the study of trans-vascular filtration and solute exchange during the drop of blood capillary pressure due to the pathological decrease of blood volume called hypovolaemia, as well as hemorrhage. We discuss the advantage of using a multi-layered model, rather than a model considering the microvessel wall as a single and homogeneous membrane.