Auswahl der wissenschaftlichen Literatur zum Thema „Calcification, Physiologic“

Calcification of the vessel wall contributes to high cardiovascular morbidity and mortality. Vascular calcification (VC) is a systemic disease with multifaceted contributing and inhibiting factors in an actively regulated process. The exact underlying mechanisms are not fully elucidated and reliable treatment options are lacking. Due to the complex pathophysiology, various research models exist evaluating different aspects of VC. This review aims to give an overview of the cell and animal models used so far to study the molecular processes of VC. Here, in vitro cell culture models of different origins, ex vivo settings using aortic tissue and various in vivo disease-induced animal models are summarized. They reflect different aspects and depict the (patho)physiologic mechanisms within the VC process.

Degenerative changes, atherosclerotic process and calcification of valvular leaflets are mostly responsible for valvular aortic valve stenosis, but congenital bicuspid aortic valve and rheumatic fever in history are also known predisposing factors. Aortic valve stenosis is frequently associated with different functional vascular alterations. The aim of this review is to demonstrate these vascular alterations evaluated by non-invasive methods and underlying physiologic and pathophysiologic processes. Orv. Hetil., 2011, 152,993–999.

Calcification of biomaterials used in prosthetic heart valves has been a challenging issue in cardiovascular surgery. The objective of this work is to compare the efficiency of polyvinyl alcohol (PVA) and tannic acid (TA) modification of xenomaterials, pre-stabilized with glutaraldehyde (GA) and ethylene glycol diglycidyl ether (EGDE), in reducing calcification. Analysis of mechanical properties evaluated under uniaxial tension, showed a significant increase in the tensile strength of the test samples compared to the control (unmodified) samples (p < 0.05). Additional treatment of GA-fixed tissue with PVA and TA significantly reduced the amount of calcium in the samples implanted into rats for a 60-day follow-up (p < 0.05). The level of calcification of samples prestabilized with EGDE and treated with PVA and TA did not differ from the control group (p = 0.063). Cumulative analysis of the study results demonstrated that the GA-fixed biomaterial modified with PVA and TA can reduce calcium-binding activity and increase strength. This indicates the prospects for clinical application of the proposed treatment methods. This being said, the issue of long-term body response requires further study of the long-term stability of the modified biomaterial under physiologic blood flow conditions.

Thesis (Ph. D.)--School of Dentistry. University of Missouri--Kansas City, 2006.
"A dissertation in oral biology and cell biology and biophysics." Advisor: Lynda F. Bonewald. Typescript. Vita. Title from "catalog record" of the print edition Description based on contents viewed Nov. 12, 2007. Includes bibliographical references (leaves 121-139). Online version of the print edition.

Orientador: Cristina Antoniali Silva
Banca: Alberto Carlos Botazzo Delbem
Banca: Carlos Ferreira dos Santos
Resumo: O tratamento da hipertensão durante a gravidez visa diminuir os riscos maternos e fetais. Entre os diferentes tipos de anti-hipertensivos que podem ser utilizados durante este período, estão os antagonistas dos receptores β-adrenérgicos. O atenolol é um antagonista seletivo de receptores 1-adrenérgicos que atravessa a barreira placentária e é excretado no leite materno chegando com facilidade ao feto de mães tratadas e aos recém-nascidos amamentados. Embora vários estudos em humanos e animais tenham avaliado os efeitos tóxicos do atenolol no período pré-natal (alterações placentárias, retardo de crescimento intra-uterino, diminuição do peso fetal) e pós-natal (diminuição do ganho de peso), pouca atenção foi direcionada aos efeitos do atenolol sobre os tecidos mineralizados, quando administrado durante a organogênese e o período pós-natal. Estudos clínicos e experimentais têm sugerido a participação do sistema nervoso autônomo simpático (SNS) no metabolismo ósseo e no crescimento dental. O objetivo do presente estudo foi avaliar se o tratamento com atenolol de ratas hipertensas (SHR) e normotensas (Wistar) durante a prenhez e lactação altera a formação dental e óssea dos filhotes. Filhotes de ratas Wistar e SHR não tratadas e tratadas com Atenolol (100mg/kg,v.o) foram sacrificados aos 30 dias de vida e as análises da densidade mineral óssea (DMO), comprimento e largura e de microdureza foram feitas nos dentes incisivos inferiores, crista óssea alveolar, fêmur, tíbia e 4a vértebra lombar (L4). As imagens digitais foram obtidas em placas ópticas, lidas em escaner a laser e analisadas no programa de computador Digora. As medidas do comprimento e largura foram feitas nas mesmas imagens utilizadas para a análise da DMO, com uso do mesmo programa de computador. A leitura da microdureza do esmalte foi realizada em microdurômetro HMV-2 Shimadzu... (Resumo completo, clicar acesso eletrônico abaixo)
Abstract: Treatment of hypertension during pregnancy aims at reducing the risks for mother and foetus. Among the different types of antihypertensive drugs that may be used during this period are the β-adrenergic antagonists. Atenolol is a selective antagonist towards 1-adrenergic receptors, which crosses the placental barrier and is excreted in breast milk coming easily to the fetus of treated mothers and breastfed newborns. Although several studies in humans and animals have evaluated the toxic effects of atenolol in prenatal (placental changes, intrauterine growth-retardation, decreased fetal weight) and postnatal (decreased weight gain) periods, little attention has been directed to the effects of atenolol on mineralized tissues, when administered during organogenesis and postnatal period. Clinical studies with humans and experimental studies with animals have suggested the involvement of the sympathetic autonomic nervous system (SNS) in bone metabolism and in dental growth. The aim of this study was to evaluate whether treatment of hypertensive rats (SHR) and normotensive ones (Wistar) during pregnancy and lactation with atenolol alters bone and dental formation of puppies. Offspring of female Wistar and SHR rats untreated and treated with Atenolol (100 mg / kg, per day) were sacrificed at 30 days and the analyses of bone mineral density (BMD), length and width, and microhardness were made in their lower incisor teeth, alveolar bone crest, femur, tibia and 4th lumbar vertebra (L4). Digital images were obtained with optical plates read in a laser scanner and manipulated in software Digora. The measurements of length and width were performed in the same images obtained for the analysis of BMD, and with the same software. The reading of the enamel microhardness was performed with Shimadzu HMV-2000 microhardness meter. The results were expressed as mean SEM and compared between the groups... (Complete abstract click electronic access below)
Mestre

RESUMO: A presente dissertação para tese de doutoramento apresenta o desenvolvimento e a validação de um método simples e original para o diagnóstico de calcificações vasculares em doentes em diálise, utilizando um score semiquantitativo criado por nós e obtido em RX simples da bacia e das mãos, denominado score de calcifi cação vascular simples. Demonstramos que este score vascular simples é preditor de risco cardiovascular nos doentes em diálise. O score de calcificação vascular simples associou-se ainda à baixa densidade mineral óssea avaliada por dual energy X -ray absortiometry (DXA) no colo do fémur. Verifi camos igualmente que, em doentes em diálise, as calcifi cações coronárias quantifi cadas pelo score de Agatston e o score de calcifi cação vascular simples se associaram a um menor volume ósseo avaliado em biopsias ósseas. Estes trabalhos corroboram a hipótese da existência de um elo de ligação entre a doença óssea e a doença vascular nos doentes em diálise, e um dos elementos que contribuem para este elo de ligação podem ser as calcificações vasculares. Este score de calcificação vascular simples avalia calcifi cações em artérias de grande, médio e pequeno calibre, e inclui os dois padrões radiológicos de calcificação: calcificação linear, associada à calcifi cação da camada média da parede arterial, e calcificação irregular, associada à calcifi cação da camada íntima arterial1. Nos diferentes trabalhos por nós publicados demonstramos que as calcificações vasculares avaliadas por este método simples e barato permitem a identificação de indivíduos com elevado risco cardiovascular. Este score vascular associa -se a maior risco de mortalidade cardiovascular2, de mortalidade de causa global3, de internamentos cardiovasculares2, de doença ardiovascular2, de doença arterial periférica2,4,de calcifi cações valvulares5 e de rigidez arterial3. As guidelines KDIGO (Kidney disease: improving global outcomes), publicadas em 2009,sugerem que os doentes renais crónicos nos estadios 3 a 5, com calcificações vasculares e valvulares, devem ser considerados como apresentando o mais elevado risco cardiovascular6. A elevada mortalidade dos doentes renais crónicos não é totalmente explicada pelos fatores de risco tradicionais7. A organização KDIGO defende, desde 2006, a hipótese da existência de um elo de ligação entre a doença óssea e a doença vascular8. Esta ligação pode ser explicada pelas alterações do metabolismo mineral e ósseo e pela sua interação com as calcificações vasculares. Verificamos, nos nossos trabalhos, uma associação entre calcifi cações vasculares e doença óssea. O baixo volume ósseo diagnosticado por análise histomorfométrica de biopsias ósseas foi preditor de maior risco de calcificações vasculares avaliadas pelo score de calcifi cação vascular simples (dados apresentados nesta dissertação, no capítulo 6) e pelo score coronário de Agatston num grupo de doentes em diálise9. A contribuição original deste artigo9 foi considerada merecedora de um editorial feito pelo Dr. Gérard London10, investigador líder na área da calcificação vascular dos doentes renais crónicos e actual Presidente da EDTA (European Dialysis and Transplantation Association). Fomos também os primeiros a descrever uma associação independente e inversa entre a densidade mineral avaliada no colo do fémur por DXA (dual energy X -ray absortiometry) com calcificações vasculares avaliadas pelo score de calcificação vascular simples, com rigidez arterial avaliada por velocidade de onda de pulsocarotidofemoral e com doença arterial periférica diagnosticada por critérios clínicos11. Fomos igualmente os primeiros a mostrar uma correlação signifi cativa entre a densidade mineral óssea avaliada por DXA no colo do fémur, mas não na coluna lombar, com a espessura cortical avaliada por análise histomorfométrica em biopsia óssea12. O nosso estudo atribui pela primeira vez à DXA um papel no diagnóstico de porosidade cortical nos doentes em diálise. A utilidade da avaliação diferencial da densidade mineral óssea cortical e trabecular necessita ainda de ser confirmada em estudos prospectivos. Este achado inovador do nosso estudo foi mencionado pela ERBP (European Renal Best Practice) no comentário feito à posição da KDIGO que considera ser reduzida a utilidade da densidade mineral óssea nos doentes em diálise13. Dois dos trabalhos incluídos nesta dissertação foram referenciados nas guidelines KDIGO 2009 para avaliar a prevalência das calcificações vasculares (KDIGO 2009: Tabela suplementar 10, Fig. 3.6) e para validar a associação entre calcificações vasculares e mortalidade cardiovascular (KDIGO 2009: Tabela suplementar 12, Fig. 3.7)6. A inclusão destes nossos dois estudos nas referências destas guidelines, que utilizaram o exigente sistema GRADE (Grades of recommendation, assessment, development, and evaluation) na classificação e selecção dos estudos, valida o interesse científico dos nossos trabalhos. O diagnóstico de calcificações vasculares tem um interesse prático para os doentes renais crónicos. A presença de calcifi cações vasculares é um sinal de alerta para a existência de um elevado risco cardiovascular, e esta informação pode ser utilizada para modificar a terapêutica nestes doentes6. Diferentes métodos podem ser usados para diagnosticar calcificações vasculares nos doentes em diálise14,15. O score de calcificação vascular simples tem a vantagem da simplicidade e de poder ser facilmente interpretado pelo nefrologista, sem necessidade de um radiologista. A reprodutibilidade deste score já foi demonstrada por diferentes grupos em estudos nacionais e internacionais16-24. Nestes estudos foi demonstrado que as calcifi cações vasculares avaliadas pelo método criado por nós são preditoras de maior risco de eventos cardiovasculares16, de amputações dos membros inferiores17, de velocidade de onda de pulso18,19, de calcificações corneanas e conjuntivais20 e de calcifi cações coronárias21. Também foi demonstrada uma associação inversa entre o score de calcificação vascular simples com os níveis séricos de PTH21, com os níveis de 25(OH)vitamina D 22,23 e com os níveis de fetuína A19,24. Todos estes estudos, realizados por diferentes grupos, que utilizaram o score de calcificação vascular simples na sua metodologia, comprovam a facilidade de utilização deste score e a concordância de resultados atestam a sua reprodutibilidade e a utilidade na avaliação dos doentes renais crónicos. ---------------------------ABSTRACT: This thesis presents the development and validation of a simple and original method to identify vascular calcifications in dialysis patients, using a semi -quantitative score that we have created and that is obtained in plain X -ray of pelvis and hands. This score was named in different publications as “simple vascular calcifi cation score”. We have demonstrated that this score is a predictor of higher cardiovascular risk in dialysis patients. The simple vascular calcification score was also associated with lower mineral bone density evaluated by DXA in femoral neck. In hemodialysis patients coronary calcifications evaluated by the coronary Agatston score and by the simple vascular calcification score were associated with lower bone volume analysed in bone biopsies. These studies corroborate the hypothesis of the existence of a link between bone disease and vascular disease in dialysis patients and one of the elements of this link may be vascular calcifications. This simple vascular calcification score identifi es calcifications in large, medium and small calibre arteries and includes the two radiological patterns of arterial calcifi cation: linear calcification which has been associated with the calcifi cation of the media layer of the arterial wall and irregular and patchy calcification which has been associated with the calcifi cation of the intima layer of the arterial wall1. In the several studies that we have published we have demonstrated that vascular calcifications evaluated by this simple and inexpensive method allow the identification of patients with high cardiovascular risk. This simple vascular calcification score is an independent predictor of cardiovascular mortality2, all -cause mortality3, cardiovascular hospitalizations2, cardiovascular disease2, peripheral artery disease2,4, valvular calcifi cations5 and arterial stiffness3.KDIGO (Kidney Disease: Improving Global Outcomes) guidelines published in 2009 suggest that chronic kidney disease patients in stages 3 to 5, with vascular and valvular calcifications should be considered to be at the highest cardiovascular risk6. The high mortality of chronic kidney disease patients is not completely explained by the traditional risk factors7 and KDIGO group supports, since 2006, the hypothesis of the existence of a link between bone disease and vascular disease8.This link may be explained by the alterations of the bone and mineral metabolism and their interaction with development and progression of vascular calcifications. We have also verifi ed in our studies the existence of an association between vascular calcifications and bone disease. Low bone volume diagnosed by histomorphometric analysis of bone biopsies, in a group of dialysis patients, was independently associated with the simple vascular calcification score (data presented in this thesis,chapter 6) and with coronary calcifications evaluated by the Agatston score9. The original contribution of this article published in CJASN9 deserved a commentary in an Editorial written by Prof. Gérard London10 leader investigator in this area and current EDTA (European Dialysis and Transplantation Association) President. We were also the fi rst group to describe an independent and inverse association between bone mineral density evaluated in the femoral neck by DXA (dual energy X -ray absortiometry) with vascular calcifications evaluated by the simple vascular calcification score, with arterial stiffness evaluated by carotid-femoral pulse wave velocity and with peripheral artery disease diagnosed by clinical criteria11. We were also the first group to demonstrate a significant correlation between bone mineral density evaluated by DXA in femoral neck but not in lumbar spine, with cortical thickness evaluated by histomorphometric analysis of bone biopsy12. Our study has attributed to DXA, for the first time, a role in the diagnosis of cortical porosity in dialysis patients. The clinical utility of the differential evaluation of bone mineral density in cortical or trabecular bone needs, however, to be confi rmed in prospective studies. This original fi nding of our study was mentioned by ERBP (European Renal Best Practice) commenting the KDIGO position in relation with the reduced utility of bone mineral density evaluation in dialysis patients13. Two of the studies included in this thesis have been integrated in a group of studies selected as references by the KDIGO guidelines published in 2009 to evaluate the prevalence of vascular calcifications in CKD patients (KDIGO 2009: Supplementary Table 10, Fig. 3.6) and to corroborate the association between vascular calcifications and cardiovascular mortality (KDIGO 2009: Supplementary Table 12, Fig. 3.7)6. The inclusion of both studies as references in the KDIGO guidelines that have used the exigent GRADE system (Grades of Recommendation, Assessment, Development, and Evaluation) in the classifi cation and selection of studies, validates the scientifi c value of our studies. The diagnosis of vascular calcifi cations has a practical interest for chronic kidney disease patients. The presence of vascular calcifications is an alert sign to the existence of a high cardiovascular risk and this information may be used to modify the treatment of these patients6. Different methods may be used to detect the presence of vascular calcifications in dialysis patients14,15. The simple vascular calcifi cation score has the advantage of being simple, inexpensive and easily evaluated by the Nephrologist without the need for a Radiologist interpretation. The reproducibility of this method has already been demonstrated by other groups in national and international studies16 -24. It was demonstrated in those studies that vascular calcifi cations evaluated by the method created by us, predict higher risk of cardiovascular events16, higher risk of lower limbs amputations17, higher pulse wave velocity18,19, corneal and conjuntival calcifi cations 20 and coronary calcifi cations21. A negative association between the simple vascular calcification score and PTH levels21, 25(OH) vitamin D levels22,23 and Fetuin A levels19,24 has also been demonstrated. All these studies performed by different groups that have used the simple vascular calcifi cation score in their methods demonstrate that this score is simple, useful and reproducible in the evaluation of chronic kidney disease patients simple, useful and reproducible in the evaluation of chronic kidney disease patients.

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O tratamento da hipertensão durante a gravidez visa diminuir os riscos maternos e fetais. Entre os diferentes tipos de anti-hipertensivos que podem ser utilizados durante este período, estão os antagonistas dos receptores β-adrenérgicos. O atenolol é um antagonista seletivo de receptores 1-adrenérgicos que atravessa a barreira placentária e é excretado no leite materno chegando com facilidade ao feto de mães tratadas e aos recém-nascidos amamentados. Embora vários estudos em humanos e animais tenham avaliado os efeitos tóxicos do atenolol no período pré-natal (alterações placentárias, retardo de crescimento intra-uterino, diminuição do peso fetal) e pós-natal (diminuição do ganho de peso), pouca atenção foi direcionada aos efeitos do atenolol sobre os tecidos mineralizados, quando administrado durante a organogênese e o período pós-natal. Estudos clínicos e experimentais têm sugerido a participação do sistema nervoso autônomo simpático (SNS) no metabolismo ósseo e no crescimento dental. O objetivo do presente estudo foi avaliar se o tratamento com atenolol de ratas hipertensas (SHR) e normotensas (Wistar) durante a prenhez e lactação altera a formação dental e óssea dos filhotes. Filhotes de ratas Wistar e SHR não tratadas e tratadas com Atenolol (100mg/kg,v.o) foram sacrificados aos 30 dias de vida e as análises da densidade mineral óssea (DMO), comprimento e largura e de microdureza foram feitas nos dentes incisivos inferiores, crista óssea alveolar, fêmur, tíbia e 4a vértebra lombar (L4). As imagens digitais foram obtidas em placas ópticas, lidas em escaner a laser e analisadas no programa de computador Digora. As medidas do comprimento e largura foram feitas nas mesmas imagens utilizadas para a análise da DMO, com uso do mesmo programa de computador. A leitura da microdureza do esmalte foi realizada em microdurômetro HMV-2 Shimadzu...
Treatment of hypertension during pregnancy aims at reducing the risks for mother and foetus. Among the different types of antihypertensive drugs that may be used during this period are the β-adrenergic antagonists. Atenolol is a selective antagonist towards 1-adrenergic receptors, which crosses the placental barrier and is excreted in breast milk coming easily to the fetus of treated mothers and breastfed newborns. Although several studies in humans and animals have evaluated the toxic effects of atenolol in prenatal (placental changes, intrauterine growth-retardation, decreased fetal weight) and postnatal (decreased weight gain) periods, little attention has been directed to the effects of atenolol on mineralized tissues, when administered during organogenesis and postnatal period. Clinical studies with humans and experimental studies with animals have suggested the involvement of the sympathetic autonomic nervous system (SNS) in bone metabolism and in dental growth. The aim of this study was to evaluate whether treatment of hypertensive rats (SHR) and normotensive ones (Wistar) during pregnancy and lactation with atenolol alters bone and dental formation of puppies. Offspring of female Wistar and SHR rats untreated and treated with Atenolol (100 mg / kg, per day) were sacrificed at 30 days and the analyses of bone mineral density (BMD), length and width, and microhardness were made in their lower incisor teeth, alveolar bone crest, femur, tibia and 4th lumbar vertebra (L4). Digital images were obtained with optical plates read in a laser scanner and manipulated in software Digora. The measurements of length and width were performed in the same images obtained for the analysis of BMD, and with the same software. The reading of the enamel microhardness was performed with Shimadzu HMV-2000 microhardness meter. The results were expressed as mean SEM and compared between the groups... (Complete abstract click electronic access below)

Includes bibliographical references (leaves 226-273.) Investigates the regulation of the expression of CYP27B1, CYP24 and vitamin D receptor (VDR) mRNA, both in the bone and in the kidney, with the aim to determine whether the regulation of the vitamin D metabolism in the bone is independent from that in the kidney. The effects of age, dietary calcium and vitamin D status on the expression of these genes in both the kidney and the bone, as well as on a number of biochemical factors known to regulate the renal metabolism of 1,25D, such as PTH, calcium and 1,25D itself, were examined. CYP27B1 mRNA expression was also studied in histological sections of rat femoral bone.

The ageing population represents a unique challenge for cardiovascular care. Ageing causes remodelling of the cardiovascular system and commonly results in distinct degenerative changes. Most of these degenerative changes have significant interactions with cardiovascular risk factors by either being a marker of disease burden or being exaggerated by co-morbid conditions. Also, age-related degenerative conditions have physiological and prognostic implications. This chapter discusses several common degenerative cardiovascular conditions in the elderly such as cardiac fibrosis, amyloidosis, mitral annular calcification, and aortic valve sclerosis. Some of these conditions (such as cardiac fibrosis and amyloidosis) are implicated in pathogenesis of heart failure with preserved ejection fraction. Others (such as mitral annular calcification and aortic valve sclerosis) do not typically cause any measurable physiological abnormality but have prognostic significance.

The ageing population represents a unique challenge for cardiovascular care. Ageing causes remodelling of the cardiovascular system and commonly results in distinct degenerative changes. Most of these degenerative changes have significant interactions with cardiovascular risk factors by either being a marker of disease burden or being exaggerated by co-morbid conditions. Also, age-related degenerative conditions have physiological and prognostic implications. This chapter discusses several common degenerative cardiovascular conditions in the elderly such as cardiac fibrosis, amyloidosis, mitral annular calcification, and aortic valve sclerosis. Some of these conditions (such as cardiac fibrosis and amyloidosis) are implicated in pathogenesis of heart failure with preserved ejection fraction. Others (such as mitral annular calcification and aortic valve sclerosis) do not typically cause any measurable physiological abnormality but have prognostic significance.

This chapter reviews the physiological and cellular functions of vitamin K in the cardiovascular system based on the latest pre-clinical and clinical evidence. Vitamin K belongs to a family of structurally similar fat-soluble vitamins, actively required by the body for the synthesis of essential proteins as well as regulate blood clotting, bone metabolism and calcium level. The authors emphasize the quintessential association between dietary vitamin K2 and cardiovascular diseases shown in various studies. The association, through the vitamin K - dependent hormones, plays a primary role in regulating calcification of different cell types, especially their role in calcification of the vascular endothelial cells. The consequences of vitamin K deficiency in the vascular system are unfavorable, shown in various clinical studies on statins - well-known inhibitors of vitamin K production in the body. New clinical insights suggest that vitamin K levels in the body and its dietary supplementation play a crucial role in cardiovascular disease prevention. There is negative influence of these antagonist’s pate in vascular composition and functions. Therefore, there is a need for prospective studies to make more in-depth exploration and increase the current understanding of this critical relationship to confidently apply such knowledge to prevent cardiovascular diseases and improve their outcomes.

Aortic valve diseases such as congenital bicuspid aortic valve (BAV) and progressive calcification in tricuspid valves affect the hemodynamics in the aortic arch. In addition to leaflet calcification, BAVs are associated with other ailments such as aortic coarctation, aneurysm and dissection [1]. It has also been observed that progressive calcification is accelerated in the case of BAVs compared to normal tricuspid valves. While it is not yet known whether the geometric distortion in BAVs is the main cause of calcification [2] in these valves, the distortion in the leaflets may give rise to altered stresses during the deformation processes which might play a role in accelerating the calcification process in BAVs. In addition, the altered flow caused by the change in geometry could alter the local fluid stresses during the opening phase, which might affect the endothelial lining of the aortic wall. Analyzing and comparing BAV and tricuspid aortic valves as a fluid-structure interaction problem will help determine the stress distribution on the leaflets during opening phase, and enable the examination of altered flow dynamics in the ascending aorta. In this study, the opening phase of a patient-specific bicuspid aortic valve is analyzed at physiological conditions and compared with the opening phase of a tricuspid aortic valve.

Congenital Bicuspid Aortic Valve (BAV) is a valvular anomaly where a patient is born with a valve with two leaflets instead of a normal tri-leaflet valve. It has also been reported that BAVs are prone to progressive calcification and also other complications such as ascending aortic dilatation, dissection and rupture [1]. The geometrical variations with the BAV may be a factor in altering the deformation and stresses on the leaflets resulting in calcification of the leaflets earlier than with normal tri-leaflet aortic valves. Altered flow patterns past BAV into the ascending aorta can also be anticipated. Analysis of flow dynamics during the opening phase, and the resultant fluid forces on the aortic root could improve our understanding of aortic aneurysms and dissections observed in patients with BAV [2]. In this study, the valvular deformation and the flow across a patient-specific BAV and root are simulated using the method of fluid structural interaction analysis. The patient-specific geometry is obtained employing 3D ultrasound images segmented as point cloud data and surfaces are constructed with commercial software GAMBIT using NURBS based connectivity. The opening phase of the valve is simulated under flow with physiological Reynolds number and with realistic material properties for the leaflets and the aortic root. Such an analysis on the dynamics of BAV with patient-specific geometry may be a useful tool in stratifying BAV patients that may be at risk in developing valvular and ascending aortic pathology.

Intravascular nitinol stents are used in the treatment of atherosclerosis and intracranial aneurysms. Despite the unique physical properties of shape memory and superelasticity, the chemical composition of NiTi has raised concerns due to the presence of nickel ions within the alloy which can have adverse effects on human health. Currently, stents are manufactured from corrosion resistant alloys which form protective titanium oxide films, insulating the bulk material from the corrosive physiologic fluid. However, nanometer thick regions of oxides are lost at locations of high strain due to significant bending, micromotion between overlapping stents or local calcification1‐2. Recent studies have revealed that some stents undergo corrosion in vivo, with significant release of metallic ions into surrounding tissues3–4. In this project, a range of techniques has been employed to modify the surface of miniature NiTi stents in order to mimic in vivo corrosion and correlate the amount of nickel ions released with the findings in explanted tissue.

Carotid endarterectomy is the procedure of choice in patients with a recent symptomatic stenosis of 70–99%. Currently, the selection of candidates eligible for carotid endarterectomy is based on stenosis size only. However, the treatment is only beneficial for patients with unstable plaques, which comprises only 16% of the patient population [1]. Hence, identifying plaque stability at an early stage would permit timely intervention, while substantially reducing overtreatment of stable plaques. The objective of this study is to distinguish between stable and unstable carotid atherosclerotic plaques by determining the plaque geometry, the plaque composition and the mechanical properties of plaque components in three dimensions (3D). Mechanical properties from healthy vessels were assessed earlier by van den Broek et al. [2] using ultrasound (US) imaging. They obtained a dynamic dataset in 2D + t. When blood pressure and vessel wall movement are known, mechanical properties can be extracted from these data using a constitutive model. However, atherosclerotic plaques are mostly asymmetric, and present calcifications will cause unfavorable acoustic shadowing when using US. In this study, the focus is on the assessment of plaque geometry, from in vitro echo-CT data, overcoming the aforementioned problems. In an experimental set-up (Fig. 1) both healthy and endarterectomy specimens were mounted, and exposed to physiological intraluminal pressures. Echo-CT was used to image the arterial segments in 3D+t. Automated geometry assessment of the arterial segments will be demonstrated and validated using microCT (μCT).