Windkessel modeling of the human arterial system

Cardiovascular diseases are a major concern of our society. Millions of patients all around the world are affected by disorders such as arrhythmias or atherosclerosis. Moreover, finding new diagnostic techniques and treatments is of increased difficulty due to the complexity of cardiovascular medicine. In this context, the upcoming generations of experts must be well prepared for overcoming such a challenge. This project aims to develop an educational tool that will allow students to improve their understanding on cardiovascular fluid mechanics and physiology and will allow them to gain practical experience before dealing with real patients. A system modelling the arterial system, available at the Universidad Carlos III de Madrid, is used for this purpose. The educational tool is composed by a theoretical simulation interface and an acquisition and control program, created using MATLAB, and a practical environment based on a physical pneumatic-hydraulic device. A laboratory practice for the students has been developed describing how to work with both platforms.Ingeniería Biomédic

Development of a novel diffuse correlation spectroscopy platform for monitoring cerebral blood flow and oxygen metabolism: from novel concepts and devices to preclinical live animal studies

New optical technologies were developed to continuously measure cerebral blood flow (CBF) and oxygen metabolism (CMRO2) non-invasively through the skull. Methods and devices were created to improve the performance of near-infrared spectroscopy (NIRS) and diffuse correlation spectroscopy (DCS) for use in experimental animals and humans. These were employed to investigate cerebral metabolism and cerebrovascular reactivity under different states of anesthesia and during models of pathological states. Burst suppression is a brain state arising naturally in pathological conditions or under deep general anesthesia, but its mechanism and consequences are not well understood. Electroencephalography (EEG) and cortical hemodynamics were simultaneously measured in rats to evaluate the coupling between cerebral oxygen metabolism and neuronal activity in the burst suppressed state. EEG bursts were used to deconvolve NIRS and DCS signals into the hemodynamic and metabolic response function for an individual burst. This response was found to be similar to the stereotypical functional hyperemia evoked by normal brain activation. Thus, spontaneous burst activity does not cause metabolic or hemodynamic dysfunction in the cortex. Furthermore, cortical metabolic activity was not associated with the initiation or termination of a burst. A novel technique, time-domain DCS (TD-DCS), was introduced to significantly increase the sensitivity of transcranial CBF measurements to the brain. A new time-correlated single photon counting (TCSPC) instrument with a custom high coherence pulsed laser source was engineered for the first-ever simultaneous measurement of photon time of flight and DCS autocorrelation decays. In this new approach, photon time tags are exploited to determine path-length-dependent autocorrelation functions. By correlating photons according to time of flight, CBF is distinguished from superficial blood flow. Experiments in phantoms and animals demonstrate TD-DCS has significantly greater sensitivity to the brain than existing transcranial techniques. Intracranial pressure (ICP) modulates both steady-state and pulsatile CBF, making CBF a potential marker for ICP. In particular, the critical closing pressure (CrCP) has been proposed as a surrogate measure of ICP. A new DCS device was developed to measure pulsatile CBF non-invasively. A novel method for estimating CrCP and ICP from DCS measurement of pulsatile microvascular blood flow in the cerebral cortex was demonstrated in rats.2018-03-08T00:00:00

Anaesthesia for colonic surgery : studies of the effects of anaesthetic techniques and other perioperative factors on colonic anastomoses and colonic blood flow

The disruption of an anastomosis is the most significant single cause of morbidity and mortality following colonic surgery. A number of factors are known to increase the risk of anastomotic breakdown in the colon, and these are reviewed. The physiology of the intestines is discussed, with particular emphasis on the effects on the bowel of anaesthetic drugs, techniques employed during anaesthesia, and other factors pertaining to the peri-operative period. A retrospective clinical study of patients who had undergone colonic anastomosis either during spinal nerve block with a light general anaesthetic or under conventional general anaesthesia is pre¬ sented and the findings discussed. There appeared to be a trend sugg¬ esting that spinal nerve block might result in a rather lower incid¬ ence of anastomotic breakdown. Because oxygen delivery is an important factor in wound heal¬ ing, and because anastomotic healing is known to be impaired by an inadequate blood flow, an animal model was developed for the measure¬ ment of colonic blood flow. The model was designed in such a way that the integrity of the nerve and blood supply was maintained, and was validated by comparison with other techniques. The effects of a number of factors of relevance to the peri-op¬ erative period were investigated using the model. Hypocapnia was found to reduce colonic blood flow, and hypercapnia to increase it. The increase in flow associated with hypercapnia diminished over a 60 min period. Moderate hypovolaemia decreased blood flow to the colon. Spinal nerve block and halothane both resulted in increased flow, al¬ though i.v. methoxamine or hypovolaemia during spinal nerve block produced substantial reductions. The clinical relevance of these findings is discussed

Assessment and Mechanisms of Autonomic Function in Health and Disease

The autonomic nervous system is a master regulator of homeostasis, and the conviction that autonomic outflow is important on a patient-by-patient, minute-to-minute basis in both health and disease is the motivation for this thesis. The dissertation explores three aims that advance our understanding of the autonomic nervous system by elucidating the molecular mechanisms of autonomic regulation, validating widely used techniques for autonomic assessment, and developing and applying a new method to assess sympathetic vascular control. The first aim of the dissertation was to investigate the role of the Rho kinase pathway as a mediator of the autonomic effects of central angiotensin-II. This study was performed in conscious, chronically instrumented rabbits that received intracerebroventricular infusions of angiotensin-II, angiotensin-II with the specific Rho kinase inhibitor Fasudil, Fasudil alone, or a vehicle control over two weeks. Baseline hemodynamics were assessed daily, and cardiac and global vasomotor sympathetic tone was assessed by the hemodynamic response to autonomic blockers. Angiotensin-II raised blood pressure and cardiac and global vasomotor sympathetic outflow in a Rho-kinase dependent manner. In a separate cohort, renal sympathetic nerve activity was directly recorded and sympathetic baroreflex sensitivity was assessed, providing clear evidence that angiotensin-II increases renal sympathetic nerve activity and impairs baroreflex control thereof via a Rho kinase-dependent mechanism. In summary, the pressor, sympatho-excitatory, and baroreflex dysfunction caused by central angiotensin-II depend on Rho kinase activation. The second aim was to investigate the relationship between measures of pulse rate variability obtained by a chronically implanted arterial pressure telemeter with measures of heart rate variability derived by the standard electrocardiogram and the ability of pulse rate variability to reflect the autonomic contributions of heart rate variability. This study was conducted in conscious rabbits chronically instrumented with epicardial leads and arterial pressure telemeters. The autonomic contribution to pulse rate variability was assessed by pharmacological blockade, and the intrinsic variability of pulse rate was assessed by ventricular pacing. This study showed that pulse rate variability is a generally acceptable surrogate for heart rate variability for time- and frequency-domain measures, but the additional contribution of respiration to and the differing nonlinear properties of pulse rate variability should be considered by investigators. The third aim was to critically test the idea that the renal sympathetic nerves do not participate in the physiological control of renal blood flow. This study was conducted in conscious rabbits that underwent unilateral renal denervation and chronic instrumentation with arterial pressure telemeters and bilateral renal blood flow probes. Using time-varying transfer function analysis, this study showed active, rhythmic vasoconstriction of the renal vasculature with baroreflex properties in normally innervated kidneys, consistent with sympathetic vasomotion, which was absent in denervated kidneys. This refutes the long-held idea that sympathetic control of the renal vasculature is not physiological and has important applications to the burgeoning field of therapeutic renal denervation for cardiovascular disease

Physiology-based Mathematical Models for the Intensive Care Unit: Application to Mechanical Ventilation

This work takes us a step closer to realizing personalized medicine, complementing empirical and heuristic way in which clinicians typically work. This thesis presents mechanistic models of physiology. These models, given continuous signals from a patient, can be fine-tuned via parameter estimation methods so that the model's outputs match the patient's. We thus obtain a virtual patient mimicking the patient at hand. Therapeutic scenarios can then be applied and optimal diagnosis and therapy can thus be attained. As such, personalized medicine can then be achieved without resorting to costly genetics. In particular we have developed a novel comprehensive mathematical model of the cardiopulmonary system that includes cardiovascular circulation, respiratory mechanics, tissue and alveolar gas exchange, as well as short-term neural control. Validity of the model was proven by the excellent agreement with real patient data, under normo-physiological as well as hypercapnic and hypoxic conditions, taken from literature. As a concrete example, a submodel of the lung mechanics was fine-tuned using real patient data and personalized respiratory parameters (resistance, R_rs, and compliance, C_rs) were estimated continually. This allows us to compute the patient's effort (Work of Breathing), continuously and more importantly noninvasively. Finally, the use of Bayesian estimation techniques, which allow incorporation of population studies and prior information about model's parameters, was proposed in the contest of patient-specific physiological models. A Bayesian Maximum a Posteriori Probability (MAP) estimator was implemented and applied to a case-study of respiratory mechanics. Its superiority against the classical Least Squares method was proven in data-poor conditions using both simulated and real animal data. This thesis can serve as a platform for a plethora of applications for cardiopulmonary personalized medicine

Numerical simulation and experimentation of pulsatile flows in axisymmetric arterial models

ABSTRACT NUMERICAL SIMULATION AND EXPERIMENTATION OF PULSATILE FLOWS IN AXISYMMETRIC ARTERIAL MODELS by TADESSE GEBREEGZIABHER December 2011 Co-advisors: 1. Dr. Emmanuel Ayorinde 2. Dr. Trilochan Singh Major: Mechanical Engineering Degree: Doctor of Philosophy The primary motivation for this dissertation is the fluid flow and structural response to unsteady blood flow in the human body. The research work is a synergistic merging of numerical simulation and experimentation. For the experiments, an all-encompassing, highly flexible experimental apparatus was designed and fabricated to facilitate a wide range of operating conditions, the range of which was chosen to accommodate mammalian cardiovascular system for both human and animal species. The parameters that were varied during the course of the experimentation include the frequency of the flow pulsation, tubular materials having various structural properties, and blockages of the tube cross sections to simulate the presence of plaque in arteries. The main outcome of the experimentation was a connection between the amplitude and frequency of the pulsations and the volumetric flow rate of the flowing fluid. Of equal importance is the extent of the response of the wall to the nature of the pulsating flow which was detected, located and characterized using a non-invasive acoustic emission equipment. The simulations that were performed represent a major advance over prior attempts to simulate pulsating flows in flexible- and rigid-walled tubes. That advance was embodied in the model that was used to characterize the flow. In most of prior studies, a particular flow regime was selected and used throughout the entire solution domain. This selection ignored the fact that flowing fluids passing through variable cross sections undergo changes of flow regime. In particular, a flow initiated in a relatively large upstream cross section may be laminar based on inlet conditions. However, as the fluid travels downstream and enters a constricted cross section, the laminar regime may undergo a transition and subsequently experience turbulence. The capability to accommodate all these flow regimes by a single model was first accomplished in this research. Of special relevance is that the capability to simulate the proper flow regime enabled a more realistic response of the bounding wall of the tube to the imposed pulsations. Comparisons were made between the experimental results and the predictions of the simulations for two purposes. One was to establish the ranges of applicability of the simulation model. The other established a body of archival-quality information based on confirming experimental and simulated results. Another unique contribution of this research is the determination of the presence of flow-induced acoustic emissions. The motivation for this part of this work is the development of a diagnostic tool to detect, locate, and characterize blockages in arterial models

Development and Evaluation of an Impedance Cardiographic System to Measure Cardiac Output and Other Cardiac Parameters, 1 July 1968 - 30 June 1969

Impedance cardiographic system to measure cardiac output and cardiovascular function

The measurement of choroidal blood flow using krypton-85

Chapter 1 contains a brief description of the anatomy of the eye followed by a review of the methods used previously to measure ocular blood flow. The theory of the Inert gas clearance method for measuring blood flow in homogeneously perfused tissues is discussed, in Chapter 2. A series of experiments designed to measure control values of choroidal blood flow in rabbits using krypton-85 is described in Chapter 5. The clearance of krypton from rabbit ocular tissue is complex. An explanation of the complex nature of the clearance curve was obtained by studying the diffusion of krypton in ocular tissue. Initially a diffusion model whose structure was based on the anatomy of the rabbit eye was developed (Chapter 4). Predicted clearance curves, obtained from this model, indicated that the half life of the initial exponential decline of the clearance curve was a measure of choroidal blood flow and that the subsequent decline in radioactivity was dependent on the diffusion of krypton in ocular tissue, A model based on the anatomy of the baboon eye was also developed. In Chapter 6 the results of measurements of the linear absorption coefficient, solubilities and diffusion coefficients of krypton in the different ocular tissues are presented. These are necessary for the numerical evaluation of the model. In Chapter 7 method has been applied to examine the effect of increased arterial carbon dioxide tension on the choroidal blood flow in rabbits and baboons. The response of the choroidal blood flow in rabbits was variable. In the baboon there was a 3.5% increase in choroidal blood flew per mmHg rise in PaCO2. Chapter 8 is a general discussion of the work presented in this thesis and its value