Thesis (M.S.M.E.)--University of Massachusetts Amherst, 2008. / Includes bibliographical references (p. 68-71).

Made available in DSpace on 2014-06-11T19:27:18Z (GMT). No. of bitstreams: 0 Previous issue date: 2011-03-18Bitstream added on 2014-06-13T19:55:45Z : No. of bitstreams: 1 araujo_ma_me_araca.pdf: 707645 bytes, checksum: fce723ba876ab19ebb750f9f92ee7b46 (MD5) / Foram analisados os efeitos cardiorrespiratórios e as variações do índice biespectral após a administração da infusão contínua de lidocaína em bezerros anestesiados com isofluorano sob ventilação controlada. Oito bezerros receberam infusão contínua de lidocaína (GL) ou salina 0,9% (GC). Após MPA com xilazina 0,05 mg/kg/IV e indução anestésica com quetamina 2mg/kg associada com midazolam o,1mg/kg, com os bezerros em decúbito lateral procedeu-se a intubação e administrou-se isofluorano 1,3%. Subsequentemente institui-se a VPPI com PPI de 15 cmH2O e fR de 6mpm. Decorridos 40 minutos sob anestesia com isofluorano com ventilação mecânica, aplicou-se lidocaína 2mg/kg e iniciou-se infusão contínua na taxa de 100 µg/kg/minuto (GL). Anotaram-se as variações da FC, PA, fR, SpO2, BIS e TR antes da MPA (MB) e 15 minutos após a MBA (MX) antes da administração da lidocaína (M0) e em intervalos de 20 minutos após o início da infusão dos fármacos (M20, M40, M60 e M80). As demais variáveis foram mensuradas a partir de M0. Após o final da infusão e desconexão, foram avaliados o período de tempo para a adoção de decúbito esternal e posição quadrupedal. Também foi mensurada a concentração sérica da lidocaína. A infusão continua de lidocaína não alterou as variáveis ventilométricas, hemogasométricas, índice biespectral e recuperação, porém diminuiu FC e IC. Conclui-se que apesar de ter causado redução da atividade cardíaca, a infusão contínua de lidocaína pode ser empregada como técnica anestésica em bezerros / Cardiorespiratory effects and bispectral index were analised after continuous rate infusion of lidocaine in calves isoflurane-anesthetized under controlled ventilation. Eight calves received continuous rate infusion of lidocaine (LG) or saline 0.9% (CG). After premedication with xylazine 0.05 mg kg -1 IV and induction of anesthesia with ketamine 2 mg kg -1 associated with the midazolam, 1 mg kg -1 , with the calves in lateral recumbence preceded the intubation and was administered isoflurane 1.3%. IPPV was instituted with PIP of 15 cmH2O and RR of 6 beats min -1 . After 40 minutes with isoflurane anesthesia and mechanical ventilation was applied lidocaine 2 mg kg -1 and continuous rate infusion was started at a rate of 100 mg kg -1 min -1 (LG). Were recorded variations in HR, AP, fR, SPO2, BIS and RT before administration of premedication (MB) and 15 minutes after administration (MX) before administering lidocaine (M0) and every twenty minutes after the start of the infusion of drugs (M20, M40 M60 and M80).The other variables were measured from M0. After the end of infusion and disconnection, were evaluated the time to adopt sternal recumbency and standing position. Also measured the serum concentration of lidocaine. Continuous rate infusion of lidocaine did not change the ventilometry, blood gas, bispectral index and recovery, but decreased HR and CI. We conclude that although there was a reduction in cardiac activity, the continuous infusion of lidocaine may be used as anesthesia in calves

It is generally accepted that alcohol impairs haemodynamic physiology in normal subjects. Alcohol is also thought to have a detrimental effect in shock states. However, most research has concentrated on haemorrhagic shock, whereas in cardiac tamponade, the pathophysiology of shock is very different. Although some studies have mentioned alcohol as a negative factor in patients with cardiac tamponade, none have adequately assessed its effect. In a clinical study of 50 patients who presented to Groote Schuur Hospital Trauma Unit with acute cardiac tamponade due to penetrating chest injury, those who were intoxicated fared the same as their sober counterparts. Although more patients in the intoxicated group were "moribund" or "in extremis" on admission, this did not lead to a higher overall mortality. Haemodynamic parameters and results of special investigations in the two groups were also similar. These findings suggested that intoxicated patients with cardiogenic shock, specifically acute cardiac tamponade, behaved differently from intoxicated patients with haemorrhagic shock. However, the multitude of variables and the stress involved in treating patients with life-threatening acute conditions, makes studies such as this difficult. Because of these limitations, an animal model of acute cardiac tamponade was developed, so that actions of alcohol on haemodynamic physiology could be studied in a controlled environment. Fourteen young pigs were randomly assigned to receive either 30% alcohol or tap-water via a gastrostomy. The former resulted in blood alcohol levels which were compatible with moderate to severe intoxication. Cardiac tamponade was then induced by instilling warmed plasmalyte-8 into the pericardia! sac using a pressure-cycled system. Despite the fact that animals in the tamponade/alcohol group were more hypotensive, and reflex increase in heart rate was inhibited, cardiac output was similar in the two groups. The actions of alcohol in isolation were also studied in eight sham-operated pigs. The only noticeable effect in this instance were higher pulmonary artery wedge pressures in the sham/non-alcohol group. In other words, cardiac performance in both the tamponade/alcohol and sham/alcohol groups was at least equal to, or even better than that in animals that did not receive alcohol. It would seem therefore, that alcohol does not have a negative effect on haemodynamic physiology of acute cardiac tamponade. Theoretically, alcohol may "protect" patients with acute cardiac tamponade by decreasing peripheral vascular resistance and "afterload". It is also possible that inhibitory actions on the respiratory centre may prevent hyperpnoea or tachypnoea, and thereby diminish competitive filling of the right and left ventricles. However, further studies of cardiac function in intoxicated subjects with tamponade using more sophisticated techniques are necessary, before mechanisms will become apparent. In practice, an aggressive approach should be adopted towards moribund patients with penetrating chest injuries; if they have acute cardiac tamponade and are intoxicated, their prognosis is not necessarily dismal. This is of particular relevance in Cape Town, where both alcohol abuse and assault are endemic. As for a therapeutic effect of alcohol, these studies do not support its use for pharmacological manipulation of cardiac tamponade.

<p dir="ltr">The movement of Cerebrospinal Fluid (CSF) within the brain's ventricles and the subarachnoid spaces of both the cranium and spine is crucial for the health and functioning of the central nervous system. Recent research has emphasized CSF movement's importance in metabolic waste clearance and its effect on the pathophysiology of neurodegenerative and neurodevelopmental disorders. Additionally, CSF movement is significantly enhanced during Non-rapid eye movement (NREM) sleep. Despite the critical role of CSF in maintaining brain health, a comprehensive understanding of the mechanisms driving its movement across different states of wakefulness and sleep is lacking. In this work, multimodal imaging was utilized to simultaneously monitor CSF movement and brain hemodynamics via functional Magnetic Resonance Imaging (MRI), neural activity through Electroencephalography (EEG), and non-neuronal systemic physiology via peripheral functional Near-Infrared Spectroscopy (fNIRS). Our findings reveal that CSF movement is influenced by multiple physiological forces concurrently. During wakefulness, both low-frequency vasomotion and respiration interact to regulate CSF movement. Furthermore, systemic physiological changes significantly impact CSF movement during light NREM sleep, even in the presence of autonomic neural activity. Notably, during deep NREM3 sleep, CSF movement magnitude increases independent of the magnitude of brain hemodynamics, suggesting a decrease in impedance to CSF movement and an enhanced exchange between CSF and interstitial fluid (ISF) in the brain. Building on these observations, significant enhancement of CSF movement was also achieved via simple respiratory interventions, thereby demonstrating their potential to be used as clinical protocols across pathologies characterized by reduced CSF movement.</p>

Currently, the surgical procedure followed by the majority of cardiac surgeons to address right ventricular dysfunction is the Fontan procedure, which connects the superior and inferior vena cava directly to the left and right pulmonary arteries bypassing the right atrium. However, this is not the most efficient configuration from a hemodynamics perspective. The goal of this study is to develop a patient-specific 4-way connector to bypass the dysfunctional right ventricle and augment the pulmonary circulation. The 4-way connector was intended to channel the blood flow from the inferior and superior vena cava directly to the right and left pulmonary arteries. By creating a connector with proper hemodynamic characteristics, one can control the jet flow interactions between the inferior and superior vena cava and streamline the flow towards the right and left pulmonary arteries. In this study, the focus was on creating a system that could identify the optimal configuration for the 4-way connector for patients from 1-20 years of age. A platform was created in ANSYS that utilized the design of experiments (DOE) function to minimize power-loss and blood damage propensity in the connector based on junction geometries. A CFD model was created to simulate the blood flow through the connector. Then the geometry of the bypass connector was parameterized for the DOE process. The selected design parameters included inlet and outlet diameters, radius at the intersection, and length of the connector pathways. The chosen range for each geometric parameter was based on the relative size of the patient’s arteries found in the literature. It was confirmed that as the patient’s age and artery size change, the optimal size and shape of the connector also changes. However, the corner radius did not decrease at the same rate as the opening diameters. This means that creating different sized connectors is not just a matter of scaling the original connector to match the desired opening diameter. However, it was found that power losses within the connector decrease and average and maximum blood traversal time through the connector increased for increasing opening radius. A follow up study was conducted to try to reduce or negate a consistent recirculation area found at the center of the connectors. To accomplish this a flow diverter was added to the center of the connector and optimized for each of the connectors found for the age groups used. From this study, it was found that the diverter did negate the recirculation area form the centers of the connectors. A separate Blood Damage Index (BDI) study was also run on this optimized connector with a diverter, the optimized connectors from the first study and a baseline connector. This showed a decrease in IVC sourced BDI for the optimized versions of the connector compared to the baseline geometries. This information could be used to create a more specific relationship between the opening radius and the flow characteristics. So in order to create patient specific connectors, either a new more complicated trend needs to be found or an optimization program would need to be run on each patient’s specific geometry when they need a new connector. / Master of Science / Currently, the surgical procedure followed by the majority of cardiac surgeons to address a nonfunctioning right portion of the heart is the Fontan procedure, which connects the two major inflow venous structures from the right side of the heart directly to the two major outflow venous structures, bypassing the right nonfunctioning right portion of the heart. However, this is not the most efficient configuration from a fluid flow perspective. The goal of this study is to develop a patient-specific 4-way connector to bypass the nonfunctioning right side of the heart and aid in overall circulation. Just like the Fontan procdure, the 4-way connector was intended to channel the blood flow from the two main inflow venous structures directly to the two major outflow venous structures. By creating a connector with proper fluid flow characteristics, one can control the flow interactions between the two inflows and streamline the flow towards the two outflow venous structures. In this study, the focus was on creating a system that could identify the optimal configuration for the 4-way connector for patients from 1-20 years of age. A platform was created in a modeling and simulation program, called ANSYS, that utilized the design of experiments (DOE) function to minimize power-loss and the likelihood of blood damage in the connector based on connector geometries. A CFD model was created to simulate the blood flow through the connector. Then the geometry of the bypass connector was parameterized for the DOE process. The selected design parameters included inlet and outlet diameters, radius at the intersection, and length of the connector pathways. The chosen range for each geometric parameter was based on the relative size of the patient’s arteries found in the literature. It was confirmed that as the patient’s age and artery size change, the optimal size and shape of the connector also changes. From the results of the first study showed a very decreasing relationship between the opening radius and the corner radius as the opening radius increased in size. It was also found that power losses within the connector decrease and average and maximum blood traversal time through the connector increased for increasing opening radius. A follow up study was conducted to try to reduce or negate a consistent recirculation area found at the center of the connectors. To accomplish this a flow diverter was added to the center of the connector and optimized for each of the connectors found for the age groups used. From this study, it was found that the diverter did negate the recirculation area form the centers of the connectors. A separate Blood Damage Index (BDI) study was also run on this optimized connector with a diverter, the optimized connectors from the first study and a baseline connector. This showed a decrease in BDI from the venous structure with the larger inlet flow for the optimized versions of the connector compared to the baseline geometries. This information could be used to create a more specific relationship between the opening radius and the flow characteristics. So in order to create patient specific connectors, either a new more complicated trend needs to be found or an optimization program would need to be run on each patient’s specific geometry when they need a new connector.

Hypotension is a common finding in hospitalized, critically ill neonatal foals. Hypotension may be a function of low cardiac output or increased cardiac output and decreased systemic vascular resistance. In the first instance, treatment would include fluids and/or inotropes and in the second, fluids and/or vasopressors. Therefore, cardiac output measurements are expected to help guide the treatment of hypotension associated with critical illness and/or anesthesia in neonatal foals. However, a practical and safe method of measuring cardiac output has not been described for the foal. Lithium dilution, a new method of cardiac output determination not requiring cardiac catheterization, has recently been reported in adult horses. We compared this method to thermodilution in isoflurane anesthetized, 30 to 42 hour old foals and found good agreement (mean bias 0.0474L/min; limits of agreement -3.03 to 3.12) between the two methods in a range of cardiac outputs from 5.4 to 20.4 liters/min. The lithium dilution technique is a practical and reliable method of measuring cardiac output in anesthetized neonatal foals, and warrants investigation in critically ill conscious foals. / Master of Science

published_or_final_version / abstract / Mechanical Engineering / Doctoral / Doctor of Philosophy

在這篇論文中，我們提出了在醫學模擬應用的血管或傷口上作相互作用的粒子血流變模型框架。通過平滑粒子流體動力學（SPH）制定的非牛頓流體，進行了血液流變學的模擬。通過建模血管壁結構虛擬粒子，流體 - 結構相互作用（FSI）是一個純粹的拉格朗日(Lagrange)顆粒模型進行建模的血管或血液的交互。我們的建議的方法基於純粹的非網格方法，可用於常見的動脈瘤和血管狹窄等病症的建立上。如需模擬開放性傷口在手術部位中發生較大的變形情況時，我們則採用質量 - 彈簧系統進行血顆粒的交互，此交互框架可應用到幾個開放性手術模擬，如骨科或胃鏡檢查為基礎的手術。無論是常見的醫療圖像：如CT血管造影（CTA）、磁共振血管造影（MRA）或基於網格的數據也可以 作為系統輸入的數據。血栓形成與溶解模型也被集成到這個流固耦合框架中。實驗結果證明採用我們建議的粒子互相作用框架在模擬血管中的凝血過程是可行的。受益於簡潔的拉格朗日粒子交互作用模擬，我們的系統可以保持在互動幀速率中。 / 首先，我們在這篇論文中建議把無網格流變模擬框架應用於血管手術的建模中。於非牛頓粘性流動的假設下，我們建立了血液結構的一般模型方程：以平滑粒子流體動力學實現多血粘度模型與低彈性血管壁模型。血流動力學和軟組織都可以於相同的拉格朗日粒子為基礎下模擬。在這個意義上說，通過延伸平滑粒子流體動力學的密度和動量求和不管顆粒的性質下，本論文提出了一個有效的流體 - 固體交互作用模型。該模型是特別有利於整合多種類型的介質（包括固體或液體）的。在這方面，我們進一步提出了一個與流體相關的血塊凝集溶解模型，可以適用於許多不同種類的醫學模擬：例如血栓栓塞。 / 其次，本論文亦提出了如何基於粒子的血液建模框架的前提下，擴展到大變形的軟組織互動。我們是以耦合雙向階段性質量 - 彈簧系統與固體顆粒，去代替無網格粒子固體的建模，用以維持真正人體組織的高保真度，此方法可以實現類似軟組織的皮膚或真皮的交互式模擬。而耦合血顆粒與平滑粒子方面，則由一個聰明的碰撞模塊處理，使得利用模擬皮膚表面之上，可以模擬出真實的表皮出血現象。該模型的動態計算進一步以物理學處理單元加速；而渲染的模型則是通過一個強大的圖形處理單元為基礎的立方體運行（marching cubes）的方法來實現。該模型已應用於全身血液管理培訓中。 / In this thesis, we propose particle-based rheological modeling frameworks for blood-vessel and blood-wound interaction in medical simulation applications. The effect of blood rheology has been simulated through a smoothed particle hydrodynamics (SPH) formulation of non-Newtonian flow. By modeling the vessel wall structure as virtual particles, a pure Lagrange particle formulation for fluid-structure interaction (FSI) is proposed for modeling the blood-vessel or blood-device interaction. Our proposed framework synthesizes common vascular complication sites such as stenosis and aneurysm based on purely mesh-less approach. For larger deformation situations happened in surgical sites such as open wound, we adopt a mass-spring system to interact with the blood particles; the blood-wound interaction framework can be applied to several open surgery simulations such as orthopedics or endoscopy-based interventions. Input of the data can be obtained from either common medical modalities like computed tomographic angiography (CTA), magnetic resonance angiography (MRA) or processing mesh-based data. A thrombus (clot) formation-dissolution model is also integrated into this fluid-solid interaction framework. Results have demonstrated the feasibility of employing our proposed particle framework in simulating blood-vessel interaction in the clotting process which is essential to vascular procedure simulations. Having benefited from the elegant formulation of Lagrangian particle interaction; the simulation can be maintained at interactive frame-rates. / In this thesis, first, a meshless rheological modeling framework for medical simulation of vascular procedures is proposed. Instead of assuming a Newtonian non-viscous flow, we have built our model based on the general constitutive equation of blood. The multi-regime of viscosity in blood model with a hypoelastic model of vessel wall has been realized under a SPH formulation. The hemodynamic and the soft tissue can all be simulated under the same Lagrangian particle-based formulation. In this sense, an efficient formulation of fluid-solid interaction is proposed through extending SPH summations of density and momentum regardless the nature of particles. This model is particularly beneficial to the integration of multiple types of media (including solids or fluids). With this regards, we further propose a flow related clot aggregation-dissolution model which can be applicable to many different kinds of medical simulation e.g. thrombo-embolization. / Second, the proposed particle-based blood modeling framework has been extended to interact with large deformation of soft tissue. Instead of modeling the solid as meshless particles, a bi-phasic mass-spring system is coupled with solid particles so that an interactive simulation of skin or dermis like soft tissue can be realized with high fidelity to real human tissue. To couple with the SPH formulation of blood particles, a smart collision handling module is exploited so that a realistic bleeding simulation on top of the skin surface can be created. The dynamic computation of this model is further accelerated by the physics processing unit; while the rendering of the model is realized through a robust graphics processing unit based marching cube approach. The proposed model has been applied to provide general blood management training. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Chui, Yim Pan. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2013. / Includes bibliographical references (leaves 98-113). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts also in Chinese. / Abstract --- p.ii / Chapter 1 --- Introduction --- p.1 / Chapter 2 --- Related works on physically based fluid-structure models --- p.7 / Chapter 2.1 --- Eulerian grid-based methods --- p.8 / Chapter 2.2 --- Lagrangian grid-based methods --- p.9 / Chapter 2.3 --- Lagrangian meshfree methods --- p.11 / Chapter 2.4 --- Fluid-structure interaction (FSI) --- p.12 / Chapter 2.5 --- Endovascular simulation --- p.14 / Chapter 2.6 --- Overview of Our Model --- p.15 / Chapter 3 --- Meshless blood-clot interaction --- p.16 / Chapter 3.1 --- Basic equations of fluid dynamics --- p.17 / Chapter 3.2 --- SPH basics --- p.18 / Chapter 3.3 --- SPH Rheological hemodynamics of blood --- p.20 / Chapter 3.4 --- SPH modeling of the hypoelastic vessel --- p.26 / Chapter 3.5 --- Fluid-solid interaction model --- p.28 / Chapter 3.6 --- Flow-related clot aggregation-dissolution model --- p.33 / Chapter 3.7 --- Time integration --- p.36 / Chapter 3.8 --- Hardware-friendly formulation --- p.37 / Chapter 3.9 --- Results --- p.39 / Chapter 3.9.1 --- Classical Dam-break problem --- p.41 / Chapter 3.9.2 --- Poiseuille flow --- p.43 / Chapter 3.9.3 --- Couette flow --- p.45 / Chapter 3.9.4 --- Mechanical model with material strength --- p.47 / Chapter 3.9.5 --- Hemoelastic feedback system --- p.49 / Chapter 3.9.6 --- Clotting in a stenosed vessel --- p.52 / Chapter 3.9.7 --- Timing results --- p.53 / Chapter 4 --- Meshless modeling of thrombo-embolization --- p.55 / Chapter 4.1 --- Modeling framework for thrombus formation within blood vessel . --- p.60 / Chapter 4.2 --- Geometric Modeling and Flow Simulation --- p.61 / Chapter 4.2.1 --- Data processing on vascular data --- p.61 / Chapter 4.2.2 --- Blood-Vessel particle distribution --- p.62 / Chapter 4.2.3 --- Blood-structure Interaction --- p.65 / Chapter 4.3 --- Visualization and Thrombosis Simulation --- p.66 / Chapter 4.3.1 --- Flow Visualization --- p.66 / Chapter 4.3.2 --- Thromb-Embolization Simulation --- p.68 / Chapter 4.4 --- Conclusion and discussion --- p.72 / Chapter 5 --- Lagrangian modeling framework for bleeding simulation --- p.76 / Chapter 5.1 --- SPH-based bleeding model --- p.78 / Chapter 5.2 --- Biphasic Soft-tissue deformation --- p.79 / Chapter 5.3 --- Interaction between blood and soft tissue --- p.83 / Chapter 5.4 --- Integrated training for blood management --- p.87 / Chapter 6 --- Discussion and Conclusion --- p.93 / Bibliography --- p.98

The purpose of my study was to determine and compare the effects of three calcium antagonists on systemic hemodynamics, ECG, blood flow distribution, tissue conductance and venous tone of the rat. The effects of a representative drug from Spedding's (1985) three subclasses of calcium antagonists on systemic hemodynamics, ECG, cardiac output and the distribution of blood flow were investigated by the microsphere technique in pentobarbital-anesthetized rats. The representative drugs were: I, nifedipine (12 and 35 µg/kg/min); II, verapamil (43 and 83 µg/kg/min) and III, flunarizine (174 and 275 µg/kg/min). Low and high doses were selected to give a decrease in mean arterial pressure of 10 and 20 mmHg, respectively, compared with control rats. At equal depressor levels, all the drugs similarly decreased total peripheral resistance while slightly but not significantly increasing cardiac output (CO) and stroke volume. Heart rate was decreased by verapamil and flunarizine, but increased by nifedipine. The high dose of nifedipine decreased contractility as measured by dP/dt and had no effect on PR-interval, while verapamil decreased dP/dt and prolonged the PR-interval. The low dose of nifedipine and both doses of flunarizine slightly but not significantly decreased dP/dt and had no effect on PR-interval. All three drugs similarly affected the distribution of blood flow. Blood flow to lungs, liver, and heart was increased while flow to the intestine, kidneys, spleen and skin was decreased. Arterial conductances in lungs, liver, heart and skeletal muscle were increased by the three drugs. These results show that representative drugs from the three subclasses of calcium antagonists had similar effects on the distribution of blood flow and arterial conductances but different chronotropic, dromotropic and inotropic effects. A final set of experiments were designed to evaluate calcium antagonist actions on venous tone, as venous tone is a primary determinant of CO and the calcium antagonists generally increase CO. The effects of three calcium antagonists, verapamil, nifedipine and flunarizine on mean arterial pressure (MAP), heart rate (HR) and mean circulatory filling pressure (MCFP), an index of total body venous tone, were investigated in the. conscious rat. Infusions of all three drugs caused a dose-dependent decrease in MAP and an increase in MCFP, compared with the corresponding values in control rats. HR was decreased by verapamil and flunarizine and slightly increased by nifedipine. Further experiments investigated whether the increase in MCFP by verapamil was indirectly caused by reflex activation of the autonomic nervous system. Rats were pretreated with a continuous infusion of the ganglionic blocker hexamethonium prior to infusion of verapamil. After treatment with hexamethonium, verapamil did not increase the MCFP. In fact the highest dose of verapamil significantly decreased MCFP. The results suggest that calcium antagonists have greater dilator effects in arterioles compared to veins. It appears that any direct venodilator effects of verapamil in conscious rats are masked due to reflex activation of the autonomic nervous system. / Medicine, Faculty of / Anesthesiology, Pharmacology and Therapeutics, Department of / Graduate

Sickle cell disease is a genetic disorder that affects 100,000 Americans and millions more worldwide. Although the sickle mutation affects one protein, which is only expressed in a single cell type, it has profound detrimental effects on nearly every organ system in the body. Young children with sickle cell disease have an 11\% chance of suffering a major stroke event by the age of 16, and a 35\% chance of developing ÒsilentÓ strokes that often result in significant learning and mental disabilities. Clinical investigations suggest that stroke development in people with sickle cell disease results from luminal narrowing of the carotid and cerebral arteries due to excess matrix deposition and fragmentation of the elastic lamina; however, the underlying cellular mechanisms that initiate arterial remodeling in sickle cell disease remain relatively unknown. Cathepsins K and V are members of the cysteine family of proteases and represent two of the most potent elastases yet identified in humans. Furthermore, the role of Cathepsins has been well established in other cardiovascular remodeling diseases, such as atherosclerosis. Due to the compelling histological similarities between vasculopathy in sickle cell disease and atherosclerosis, we tested the hypothesis that the unique inflammatory milieu, in conjunction with the biomechanical vascular environment of sickle cell disease upregulates cathepsin K and V activity in large artery endothelial cells, ultimately leading to arterial remodeling and stroke. Currently, there are few therapeutic options for the prevention of stroke in sickle cell disease; those that do exist carry significant health risks and side effects. Together, this body of work has generated a more mechanistic understanding of how the sickle milieu stimulates the endothelium to initiate arterial remodeling, which has enabled us to identify important pathways (JNK, NF$\kappa$B) downstream of inflammatory and biomechanical stimuli and validate new therapeutic targets within the JNK pathway to establish preclinical proof of efficacy for the prevention of arterial remodeling in sickle cell disease.