M.Tech. (Chiropractic) / Please refer to full text to view abstract

A dissertation submitted to the Faculty of Science, University of the Witwatersrand, Johannesburg, in fulfilment of requirements for the degree of Master of Science. February 16, 2015. / The Adomian decomposition method is an effective procedure for the analytical solution of a wide class of dynamical systems without linearization or weak nonlinearity assumptions, closure approximations, perturbation theory, or restrictive assumptions on stochasticity. Our aim here is to apply the Adomian decomposition method to steady two-dimensional blood flow through a constricted artery in the presence of a uniform transverse magnetic field. Blood flow is the study of measuring blood pressure and determining flow through arteries. Blood flow is assumed to be Newtonian and is governed by the equation of continuity and the momentum balanced equation (which are known as the Navier-Stokes equations). This model is consistent with the principles of ferro-hydrodynamics and magnetohydrodynamics and takes into account both magnetization and electrical conductivity of blood. We apply the Adomian decomposition method to the equations governing blood flow through arteries in the presence of an external transverse magnetic field. The results show that the e ect of a uniform external transverse magnetic field applied to blood flow through arteries favors the physiological condition of blood. The motion of blood in stenosed arteries can be regulated by applying a magnetic field externally and increasing/decreasing the intensity of the applied field.

Increasing numbers of old and sick patients who are no longer eligible for prolonged invasive implantation surgery have encouraged many researchers to investigate the development of a Mechanical Circulatory Support (MCS) device with more reliability and less possible invasive complications, which would benefit the majority of patients. This thesis will test experimentally and numerically the feasibility of installing an MCS device, as a bridge to destination, in the descending aorta, in a series configuration with the heart. To this end, a multi-chamber Simulator of the Cardio-Vascular blood-flow Loop (SCVL) was designed to simulate the in-vitro flow rates, pressures and other parameters representing normal and diseased conditions of the human cardiovascular system. The multi-chamber SCVL includes models for all four chambers of the heart, and the systemic as well as the pulmonic circulations. Next, a comprehensive study was conducted using the SCVL system to compare the novel in-series placement of the pump, in the descending aorta, with traditional in-parallel placements. Then, a comprehensive numerical study was conducted using the modified Concentrated Lumped Parameter (CLP) model developed by the same team. The numerical results are compared and verified by the experimental results under various conditions. The results for the pump installed in the descending aorta show that the pressure drop, upstream of the pump, facilitates the cardiac output as a result of after-load reduction. However, at the same time the generated pressure drop at the proximal part of the descending aorta induces a slight drop in the carotid perfusion which will be autoregulated by the brain in a native system. Further, the pressure rise downstream of the pump improves the blood perfusion in the renal artery. The pulse wave analysis show that the placement of the pump in the descending aorta leads to improved pulsatility which is beneficial for end-organ functionality in the native cardiovascular system.

Intracranial pressure (ICP) is an important monitoring modality in the clinical management of several neurological diseases carrying the risk of fatal intracranial hypertension. However, this parameter is not always considered due to its invasive assessment. In this scenario, a non-invasive estimation of ICP (nICP) may be essential, and indeed it has become a Holy Grail in Clinical Neurosciences: extensively searched, albeit never found. This thesis is devoted to the assessment, applications and development of transcranial Doppler (TCD)-based non-invasive methods for ICP and cerebral perfusion pressure (CPP) monitoring. The thesis is divided into three sections: I) The accuracy of existing TCD-based nICP estimators in various scenarios of varying ICP (traumatic brain injury, rise of ICP during plateau waves, and rise in ICP induced by infusion of cerebrospinal fluid during infusion test). The estimators of nICP consisted of a mathematical black box model, methods based on non-invasive CPP, and a method based on TCD pulsatility index. II) The feasibility of the best performing nICP estimator in clinical practice, including patients with closed TBI and brain midline shift, patients with acute liver failure during liver transplant surgery, and patients during non-neurosurgical surgery in the beach chair position. III) The description and assessment of a novel methodology for non-invasive assessment of cerebral perfusion pressure (nCPP) based on spectral arterial blood volume accounting. As main results, TCD-based non-invasive methods could replicate changes in direct ICP across time confidently, and could provide reasonable accuracy in comparison to the standard invasive techniques. Furthermore, in feasibility studies, nICP in association with other TCD physiological parameters provided a comprehensive interpretation of cerebral haemodynamics in conditions presenting impairment of cerebral blood flow circulation. The new method of nCPP estimation could identify changes in CPP across time reliably in conditions of decreasing and increasing CPP. These findings support the use of TCD-based nICP methods in a variety of clinical conditions requiring management of ICP and brain perfusion. More importantly, the low costs associated with nICP methods, since TCD is a widely available medical device, could contribute to its widespread use as a reliable alternative for ICP monitoring in everyday clinical practice.

Ho Sin Yee, Stella. / "August 2002." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2002. / Includes bibliographical references (p. 167-193). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

Doctor of Philosophy / Department of Kinesiology / Carl Ade / During exercise, muscle blood flow (Q ̇m) increases to match metabolic demand of the active skeletal muscle. In order for this matching to take place, ‘competition’ between local vasodilating metabolites and sympathetically mediated vasoconstriction, termed “functional sympatholysis,” must take place. A key feature of functional sympatholysis is that it is driven largely by metabolic rate (i.e., a higher work rates lead to greater sympatholysis), but may also be largely dependent on nitric oxide bioavailability and oxidative stress in certain disease states (e.g., hypertension). Thus, evaluation of these factors may provide valuable insight into the vascular control mechanisms during exercise in both health and disease. Therefore, the purpose of this dissertation was to 1) determine the role metabolic rate and blood flow on mediating functional sympatholysis, 2) determine the role of nitric oxide bioavailability on functional sympatholysis with high salt intake, a risk factor for primary hypertension, and 3) determine the effect of increases in nitric oxide bioavailability on functional sympatholysis in primary hypertension patients. In the first investigation (Chapter 1), we increased the relaxation phase of the contraction-relaxation cycle to increase active skeletal muscle blood flow (Q ̇m) and see if this would impact vasoconstriction of the active skeletal muscle. We showed that a decreased relaxation time led to greater functional sympatholysis. Interestingly, despite a lower metabolic rate (15% and 20% MVC), we showed that there was no difference in vasoconstriction between the increased relaxation times. These results may show that increases in Q ̇m play a role in functional sympatholysis when mechanical compression is minimized. In the second investigation (Chapter 2), we sought to determine if high dietary sodium (HS) intake would impact functional sympatholysis. We showed that HS intake (15g/day for 7 days) did not impact functional sympatholysis during exercise. Importantly, we show a significant increase in mean arterial pressure (i.e., pressor response) during handgrip exercise. These findings show the deleterious changes in blood pressure, but further work is needed to pinpoint specific mechanisms causing the responses. In the final investigation (Chapter 3), we used an acute nitrate rich (NR) supplement to improve NO bioavailability in hypertensive post-menopausal women (PMW), and observe the impact on functional sympatholysis. We provide novel evidence that functional sympatholysis is improved (~50%) with a NR supplement. The finding that a NR supplement can attenuate vasoconstriction in hypertensive PMW sheds light on the complexities of hypertension, functional sympatholysis and NO bioavailability. The current results indicate that the ‘competition’ between vasodilating metabolites and sympathetically mediated vasoconstriction can be independently modified in health and disease. In individuals with impairment to local vasodilation (e.g., hypertension), the ability to increase functional sympatholysis and muscle blood flow may lead to improvements in cardiovascular health. Taken together, the present results suggest that modifying duty cycle, sodium intake, and NO bioavailability are important factors to be considered with regard to overall cardiovascular health.

Emphysema, a subset of COPD, occurs due to an abnormal inflammatory response to noxious gases or particles leading an influx of immunologic cells. Recent studies have demonstrated endothelial dysfunction in COPD subjects and are suggestive of a vascular phenotype present in COPD that is not fully characterized. We hypothesize that processes affecting the pulmonary vasculature lead to early changes important in the pathogenesis of COPD. This work focuses on the use of multidetector-row computed tomography (MDCT)-based measures of pulmonary blood flow (PBF), mean transit time (MTT) and pulmonary vascular volume (TPVV) to gain new insights into vasculature-related changes present in COPD. As a precursor to using perfusion MDCT imaging to phenotype lung disease, we demonstrated good regional correlation of PBF measurements obtained with MDCT imaging and fluorescent microspheres (FMS) at a FMS piece size resolution of 1.9 cm3 and regional volume level of 8-10 cm3. Additionally, we developed an ex vivo perfusion system, and applied quantitative image analysis techniques to study the lung preparation's stability over 120 minutes. We further validated CT-based PBF and MTT measurements by demonstrating physiologically appropriate responses to a range of flow rates with this new system. Finally, quantitative MDCT-based measurements were used to characterize a novel phenotype of emphysema and test hypotheses regarding vasculature-related changes in smokers and COPD subjects. We demonstrated increased heterogeneity in regional MTT and PBF measurements in smokers with preclinical emphysema compared with smokers with normal lung function and imaging studies and nonsmokers. This data is supportive of the notion that inflammatory-based vascular responses to hypoxia are occurring in smokers susceptible to COPD, but are successfully blocked in smokers without signs of emphysema. A new CT-based measure, TPVV, was studied and we demonstrate its association with total lung volume and body size metrics. TPVV measurements correlated with measures of COPD severity. A trend linking increased TPVV with increased endothelial dysfunction was observed, suggesting that pathological changes of COPD have an effect on the pulmonary vasculature. This work demonstrates the importance of functional information that can compliment structural, anatomical information to answer questions based on the lung physiology and pathological disease processes.

Aging is associated with attenuated blood flow and vasodilator responses during rhythmic exercise. Older adults also demonstrate attenuated blood flow and vasodilator responses following single skeletal muscle contractions (contraction-induced rapid onset vasodilation, ROV) within the forearm. These age-associated attenuations within the forearm have been demonstrated to be a result of endothelial and neural mechanisms. The objective of this research was to examine: 1) whether age-associated attenuations within the forearm are from mechanical factors; 2) whether age-associated attentions in ROV are present within the leg, as well as explore potential mechanisms for these age-associated attenuations in ROV; 3) examine whether aging is associated with a slower rate of adjustment in vasodilation (vasodilator kinetics) during rhythmic exercise preceding steady-state exercise; and 4) examine approaches to ameliorate age-related attenuations in blood flow and vasodilation within the leg across the entire exercise transient (onset to steady-state). The novel findings of this research are that 1) age-associated attenuations in ROV within the forearm are independent of mechanical factors; 2) older adults demonstrate attenuated ROV responses within the leg; 3) age-related attenuations in ROV within the leg are not explained by enhanced sympathetic adrenergic vasoconstriction; 4) older adults exhibit prolonged vasodilator kinetics preceding steady-state exercise; and 5) when examined in a cross-sectional design chronic exercise training improves ROV, vasodilator kinetics, as well as steady-state blood flow and vasodilator responses in older adults; 6) acute supplementation with dietary nitrate fails to exert any effect on blood flow and vasodilator responses during any domain of exercise. Collectively, this work establishes that aging is associated with reductions in blood flow and vasodilation across the entire exercise transient (onset to steady-state) within the leg, which is offset by chronic exercise training. Mechanistically, the current data suggests that mechanical and sympathetic factors do not explain age-related reductions in ROV in the arm and leg, respectively. Furthermore, acute supplementation of dietary nitrate does not impact leg blood flow and vasodilator responses in older adults during any domain of the exercise transient.

Abstract not available

<p>Positron Emission Tomography, PET, is a noninvasive medical imaging technique to get functional information of the kinetics of radioactive compound injected in the body. The data used in this thesis comes from a total of five H₂¹⁵O PET studies of one patient. This was done in order to study the blood flow in liver metastasis of the patient, before and after treatment.</p><p>A one compartment model was used to do the ROI based analyses. With a least square method in Matlab the unknown parameters in the model, such as the kinetic rate constants, the dispersion and the fraction of blood in the tissue, was extracted. Also a brief analysis of different parts of the metastases, edge and center, was done to see the variations within the metastases. The results show some increase of the blood flow after the treatment, and two of the three studied metastases showed a distinct difference of the activity in the center versus the edge. Given in the thesis are also some basic PET and compartmental modeling theory.</p> / <p>Positronemissionstomografi, PET, är en icke-invasiv medicinsk bildteknik för att få funktionell information om kinetiken av radioaktiva föreningar injicerade i kroppen. Det data som används i denna kandidatuppsats kommer från totalt fem H₂¹⁵O PET-studier av en patient. Detta gjordes för att studera blodflödet i levermetastaser hos patienten före och efter behandling.</p><p>En 1-kompartmentmodell användes för att göra ROI-baserade analyser. Med en minsta kvadrat-metod i Matlab kunde de okända parametrarna i modellen, såsom den kinetiska hastighetskonstanten, spridningen och andelen blod i vävnaden, fås ut. En kort analys gjordes också av olika delar av metastaserna, kanten och mitten, för att se variationerna inuti metastaserna. Resultaten visar en viss ökning av blodflödet efter behandlingen, och två av de tre studerade metastaser visade en tydlig skillnad av aktiviteten i mitten jämfört med kanten. I rapporten ges också grundläggande teori om bland annat PET och kompartmentmodellering.</p>