Function of arteries and veins in conditions of simulated cardiac arrest

Introduction: The study examined the behavior of vasculature in conditions of eliminated cardiac function using mathematical modeling. In addition, we addressed the question of whether the stretch-recoil capability of veins, at least in part accounts for the slower response to simulated cardiac arrest. Methods: In the first set of computational experiments, blood flow and pressure patterns in veins and arteries during the first few seconds after cardiac arrest were assessed via a validated multi-scale mathematical model of the whole cardiovascular system, comprising cardiac dynamics, arterial and venous blood flow dynamics, and microcirculation. In the second set of experiments, the effects of stretch-recoil zones of venous vessels with different diameters and velocities on blood velocity and dynamic pressure analyzed using computational fluid dynamics (CFD) modeling. Results: In the first set of experiments, measurement of changes in velocity, dynamic pressure, and fluid flow revealed that the venous system responded to cardiac arrest more slowly compared to the arteries. This disparity might be due to the intrinsic characteristics of the venous system, including stretch-recoil and elastic fiber composition. In the second set of experiments, we attempted to determine the role of the stretch-recoil capability of veins in the slower response to cardiac arrest. During the second set of experiments, we found that this recoil behavior increased dynamic pressure, velocity, and blood flow. The enhancement in dynamic pressure through combining the results from both experiments yielded a 15-40% increase in maximum dynamic pressure due to stretch-recoil, depending on vein diameter under normal conditions. Conclusion: In the situation of cardiac arrest, the vein geometry changes continue, promoting smooth responses of the venous system. Moreover, the importance of such vein behavior in blood displacement may grow as the pressure on the venous side gradually decreases with time. Our experiments suggest that the driving force for venous return is the pressure difference that remains within the venous system after the energy coming from every ventricular systole spent to overcome the resistance created by arterial and capillary systems

Inner-ear circulation in humans is disrupted by extracranial venous outflow strictures: Implications for Ménière's disease

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

A holistic multi-scale mathematical model of the murine extracellular fluid systems and study of the brain interactive dynamics

Recent advances in medical science regarding the interaction and functional role of fluid compartments in the central nervous system have attracted the attention of many researchers across various disciplines. Neurotoxins are constantly cleared from the brain parenchyma through the intramural periarterial drainage system, glymphatic system and meningeal lymphatic system. Impairment of these systems can potentially contribute to the onset of neurological disorders. The goal of this thesis is to contribute to the understanding of brain fluid dynamics and to the role of vascular pathologies in the context of neurological disorders. To achieve this goal, we designed the first multi-scale, closed-loop mathematical model of the murine fluid system, incorporating: heart dynamics, major arteries and veins, microcirculation, pulmonary circulation, venous valves, cerebrospinal fluid (CSF), brain interstitial fluid (ISF), Starling resistors, Monro-Kellie hypothesis, brain lymphatic drainage and the modern concept of CSF/ISF drainage and absorption based on the {\em Bulat-Klarica-Orešković} hypothesis. The mathematical model relies on one-dimensional Partial Differential Equations (PDEs) for blood vessels and on Ordinary Differential Equations (ODEs) for lumped parameter models. The systems of PDEs and ODEs are solved through a high-order finite volume ADER method and through an implicit Euler method. The computational results are validated against literature values and magnetic resonance flow measurements. Furthermore, the model is validated against {\em in-vivo} intracranial pressure waveforms acquired in healthy mice and in mice with impairment of the intracranial venous outflow. Through a systematic use of our computational model in healthy and pathological cases, we provide a complete and holistic neurovascular view of the main murine fluid dynamics. We propose a hypothesis on the working principles of the glymphatic system, opening a new door towards a comprehensive understanding of the mechanisms which link vascular and neurological disorders. In particular, we show how impairment of the cerebral venous outflow might potentially lead to accumulation of solutes in the parenchyma, by altering CSF and ISF dynamics. This thesis also concerns the development of a high-order ADER-type numerical method for systems of hyperbolic balance laws in networks, based on a new implicit solver for the junction-generalized Riemann problem. The resulting ADER scheme can deal with stiff source terms and can be applied to non-linear systems of hyperbolic balance laws in domains consisting of networks of one-dimensional sub-domains. Also, we design a novel one-dimensional mathematical model for collecting lymphatics coupled with a Electro-Fluid-Mechanical Contraction (EFMC) model for dynamical contractions. The resulting mathematical model gives each lymphangion the autonomous capability to trigger action potentials based on local fluid-dynamical factors

Perspectives of Implementation of Closed-Loop Deep Brain Stimulation: From Neurological to Psychiatric Disorders.

BACKGROUND Deep brain stimulation (DBS) is a highly efficient, evidence-based therapy to alleviate symptoms and improve quality of life in movement disorders such as Parkinson's disease, essential tremor, and dystonia, which is also being applied in several psychiatric disorders, such as obsessive-compulsive disorder and depression, when they are otherwise resistant to therapy. SUMMARY At present, DBS is clinically applied in the so-called open-loop approach, with fixed stimulation parameters, irrespective of the patients' clinical state(s). This approach ignores the brain states or feedback from the central nervous system or peripheral recordings, thus potentially limiting its efficacy and inducing side effects by stimulation of the targeted networks below or above the therapeutic level. KEY MESSAGES The currently emerging closed-loop (CL) approaches are designed to adapt stimulation parameters to the electrophysiological surrogates of disease symptoms and states. CL-DBS paves the way for adaptive personalized DBS protocols. This review elaborates on the perspectives of the CL technology and discusses its opportunities as well as its potential pitfalls for both clinical and research use in neuropsychiatric disorders