Academic literature on the topic 'Vascular disturbances'

Retina of rats OXYS 6 months of age by treatment of 4-methyl-2,6-diisobornylphenol (dibornol) was researched. Mainly, rats OXYS have of vascular disturbances such as reduction open functional vasculars of choroidea, destruction of retinal pigmental epithelium and retinal neurons. Dibornol was protected of retina increased area of open vascular and safety of retinal neurons. Besides dibornol was prevented thrombosis in retinal vasculars.

21 patient with different clinical patterns of non-insult course of developing vascular brain disturbance were included into investigation. Standard neurological examination was fol lowed by MR-tomography. Different degress of intellectualmnestic disorders and various locomotor disturbances correspond to the depicted in tomograms multiple brain lesions with cortical and subcortical foci. Comparison of clinical and MRT-data didnt reveal in full measure correlations between them.

Flow disturbances in tapered arterial grafts of angles of taper between 0.5 and 1.0 deg were measured in vitro using a pulsed ultrasound Doppler velocimeter. The increase in transition Reynolds numbers with angle of taper and axial distance was determined for steady flow. The instantaneous centerline velocities were measured distal to a 50 percent area stenosis (as a model of a proximal anastomosis), in steady and pulsatile flow, from which the disturbance intensities were calculated. A significant reduction in post-stenotic disturbance intensity was recorded in the tapered grafts, relative to a conventional cylindrical graft. In pulsatile flow with a large backflow component, however, there was an increase in disturbance intensity due to diverging flow during flow reversal. This was observed only in the 1.0 deg tapered graft. These findings indicate that taper is an important consideration in the design of vascular prostheses.

Rosacea is a chronic skin disorder, characterized by redness and flushing of the cheeks, nose, chin or forehead. It has been proposed that rosacea is a result of frequent blushing (Miller, 1921; Klaber & Whittkower, 1939). However, the relationship between rosacea and blushing is uncertain. The aim of the present research was to investigate the relationship between psychological stress and vascular disturbances in rosacea. Five studies were conducted. The first study explored the relationship between rosacea and mental health while the next two investigated vascular responses in rosacea sufferers and controls to acetylcholine (which induces endothelial vasodilatation and axon reflexes) and psychological stress (embarrassment). The fourth study aimed to examine the relationship between psychological indicators and rosacea symptoms on a daily basis. The fifth study consisted of three case studies looking at the use of Cognitive Behavioural Therapy (CBT) and Task Concentration Training (TCT) with rosacea sufferers presenting with social anxiety and fear of blushing symptoms. In study 1, sixty-two participants were asked to complete the Blushing Propensity Scale (BPS), Fear of Negative Evaluation (FNE), Depression, Anxiety and Stress Scale (DASS), Social Interaction Anxiety Scale (SIAS) and Social Phobia Scale (SPS). Outcomes from the first study indicated that Type 2 rosacea sufferers (n= 12) perceived themselves as blushing more frequently and intensely than Type 1 rosacea sufferers (n=19) or controls (n=31). This suggested that Type 2 rosacea sufferers experiencing frequent blushing may have a lower sensitivity threshold to blushing episodes. In addition, Type 2 rosacea sufferers perceived themselves as more stressed than Type 1 rosacea sufferers or controls, possibly indicating that managing the condition can be stressful. Contrary to previous reports (Gupta et al., 2006; National Rosacea Society, 2005) severity of rosacea was not associated with depression, social anxiety or fear of negative evaluation. However, a few participants who reported high social anxiety and stress scores were offered psychological intervention (Study 5). The aim of the second study was to investigate vascular responses in rosacea sufferers. Cutaneous endothelial and axon reflex function was assessed using an acetylcholine dose response curve. The axon reflex was assessed by inducing a flare with ACh iontophoresis. Outcomes from this study indicated that Type 2 rosacea sufferers had a greater axon reflex response than Type 1 rosacea sufferers. Thus over-reactivity of the axon reflex in Type 2 rosacea sufferers might contribute to prolonged vasodilatation. However, cutaneous endothelial responses to ACh were similar in rosacea and control groups. The results suggested that neural pathways mediated the flushing response rather than cutaneous endothelial function. The third study investigated facial blood flow while participants attempted laboratory induced embarrassment tasks. Type 2 rosacea sufferers were found to have a greater blood flow in the facial region than Type 1 rosacea sufferers during singing and speech tasks, suggesting that Type 2 rosacea sufferers blushed more than type 1 rosacea sufferers or controls. Furthermore, Type 2 rosacea sufferers reported higher embarrassment and blushing ratings than Type 1 rosacea sufferers. This indicated that Type 2 rosacea sufferers perceived themselves as emotionally more aroused than other participants. Taken together, it would appear that a combination of physiological and cognitive factors increased facial blood flow in Type 2 rosacea sufferers in laboratory induced embarrassment tasks. The fourth study explored the relationship between stress and symptoms of rosacea. Using a diary, 15 rosacea sufferers recorded their stress, anxiety and mood and their intensity of rosacea symptoms daily. Stress was associated with increased stinging/facial redness on the same day for 1 to 2 months. Furthermore, it was associated with increased stinging ratings the next day. However, feeling anxious or having low mood was not related to increase stinging the next day. The presence of increased stress found in rosacea participants on the day where stinging and redness occurred should be taken into consideration when formulating psychological interventions for rosacea sufferers. In study 5, individual psychological intervention was provided to three participants experiencing stress, fear of blushing and social anxiety symptoms. Cognitive Behavioural Therapy (CBT) and Task Concentration Training (TCT) were helpful in managing stress, anxiety and fear of blushing symptoms in individual rosacea sufferers. Encouragingly, all participants reported a gain in their repertoire of strategies and showed a decrease in anxiety symptoms on assessment questionnaires following their intervention. Replication of the intervention protocol and investigation of other psychological approaches are required to establish best practise outcome for rosacea sufferers who require psychological interventions. The present findings suggest that over-reactivity of axon reflexes contributes to facial flushing. In addition, emotional flushing in rosacea sufferers appears to be maintained by a combination of cognitive and physiological factors. On a clinical level, the study recommends that emotional stress associated with facial flushing in rosacea sufferers to be targeted for psychological intervention.

La present tesi analitza els efectes de la fragmentació del bosc i les pertorbacions humanes associades sobre l'estructura, la composició i l'estat de conservació dels boscos en un paisatge peri-urbà mediterrani (la plana del Vallès), tenint en compte factors climàtics, topogràfics, de pertorbació humana i paisatgístics que operen a diverses escales. També es fa especial èmfasi en l'interès dels resultats obtinguts pel que fa a la conservació i la gestió de la biodiversitat forestal en aquestes àrees fortament humanitzades. Més concretament, s'analitzat:
- La importància de les variables ambientals, les pertorbacions antròpiques i l'estructura de la clapa i del paisatge sobre el recobriment arbori de Quercus i Pinus.
- La importància dels grups de variables esmentades sobre la composició florística de les clapes de bosc de la plana del Vallès. També la resposta individual de cada espècie per tal d'identificar espècies indicadores.
- Les preferències antròpiques a l'hora de gestionar i freqüentar les clapes de bosc peri-urbanes en relació a les característiques estructurals d'aquestes.
- L'efecte de la mida de la clapa de bosc, dels usos del sòl adjacents, de la distància al marge del bosc i de la interacció d'aquests tres factors sobre la riquesa i la composició florística del sotabosc.

Vascular dysfunction is a pivotal step in the aetiology of cardiovascular disease, the leading cause of global mortality. Certain metabolic disturbances (postprandial hypertriglyceridemia - PHTG, and impaired glucose tolerance - IGT) have been identified as risk factors for vascular dysfunction, via an oxidative stress mechanism. Exercise has long been regarded as beneficial in tackling CVD but its role on oxidative stress and su~sequent vascular function is less well defined. The principal . . aim of this thesis is to examine the effects of exercise intervention on oxidative stress generation and vascular function in conditions of metabolic disturbance. The findings of Study 1 demonstrate that an acute bout of moderate intensity aerobic exercise did not change arterial function (as measured by pulse wave velocity - PWV) when compared to rest alone. However, a 1 hour bout of moderate exercise did increase the levels of the antioxidants lycopene and retinol suggesting a decrease in oxidative stress. Studies 2 and 3 illustrates that acute moderate intensity exercise can ameliorate the. postprandial vascular dysfunction induced by the ingestion of a highfat meal via a reduction in oxidative stress (LOOH) and an increase in antioxidant activity (Study 2; SOD, Study 3; retinol and lycopene). Study 3 demonstrated that an acute bout ofpre meal exercise had no effect on measures ofgastrointestinal transit. Study 4 illustrates that acute aerobic exercise can improve arterial function in obese individuals with IGT, a group who are known to be more susceptible to vascular disease. These changes were directly correlated with reductions in glucose concentrations but were not associated with changes in lipid metabolism and oxidative stress biomarkers. An exercise training regime (Study 5) was shown to improve arterial function in the same group of obese subjects with IGT. This was in combination to reductions in body mass, glucose and TG concentrations, and oxidative stress. The improvements in arterial function are perhaps due to the effects of exercise on glucose and lipid metabolism and the subsequent effect on free radical generation. The results of the studies described within this thesis provide evidence for acute and chronic exercise as key interventions to modulate the vascular dysfunction associated with PHTG and IGT. However, further research is required to define the precise biochemical mechanisms that perpetuate such adaptations.

Verhaltensstörungen bei Demenz sind von zentraler klinischer Bedeutung. Zur Beurteilung solcher Phänomene liegen eine Anzahl standardisierter Beobachtungsbögen vor. Problematisch sind diese Skalen im Hinblick auf ihre Reliabilität bei der Anwendung durch Angehörige und Pflegende. Wir schlagen daher die aktometrische Darstellung von motorischer Aktivität, wie sie etwa aus der Schlafforschung bekannt ist, vor. In dieser Dissertation wurde zunächst die Reliabilität und konkurrente Validität der Messung von motorischer Unruhe bei Demenz mittels eines aktometrischen Gerätes untersucht. Die Ergebnisse zeigen, dass die aktometrische Messung von Verhaltensstörungen eine valide und reliable Methode auch bei schwerer Demenz darstellt. Im zweiten Teils dieser Arbeit wurde unter quasiexperimenteller Kontrolle von Modulatoren der circadianen Rhythmizität Unterschiede der circadianen Rhythmik zwischen vaskulärer Demenz und Demenz vom Alzheimer-Typ untersucht. Dabei konnte gezeigt werden, dass es bei Patienten mit Demenz vom Alzheimer-Typ und bei Patienten mit vaskulärer Demenz in Abhängigkeit von der motorischen AktivitŠt zu einer charakteristischen Phasenverschiebung der circadianen Rhythmik kommt. Dieser Zusammenhang ist jedoch bei Alzheimer-Demenz, bei der von einer neurobiologischen Störung des suprachiasmatischen Nukleus ausgegangen werden kann, stärker ausgeprägt. Dieses Befundmuster unterstützt theoretische Modelle der circadianen Rhythmik und ihrer Störung bei Demenz und legt nahe, dass der suprachiasmatischen Nukleus bei Demenz vom Alzheimer-Typ eine zentrale Rolle bei der circadianen Regulation des Verhaltens einnimmt.
Behavioural signs and symptoms in dementia are of central clinical significance. There are a number of standardised rating scales available for the assessment of motor phenomena in dementia. However, there is no objective method of assessing these symptoms. In addition, the reliability of these scales, especially when used by caregivers from within families, has been questioned. In order to overcome this flaw, we propose the use of an actometric device for assessing behaviour motor symptoms in dementia. In the first part of this dissertation we assessed the reliability and the concurrent validity of an actometric device against two behavioural scales. Results show satisfactory validity and good reliability of this method. In the second part of this dissertation, we reanalysed data from our validation study, investigating whether the pattern of circadian rhythm disturbances is different in patients suffering from Alzheimer disease and patients suffering from vascular dementia, controlling experimentally for the severity of behaviour disturbances. With regards to circadian motor activity, we found increased nocturnal activity and fragmentation of diurnal rhythm in both groups. In patients showing an equal severity of behaviour disturbances, the phase-delay of the rest-activity rhythm was delayed in patients with Alzheimer disease as compared to patients with vascular dementia. These findings suggest that, in Alzheimer disease, structural changes in the SCN might induce disturbance in the circadian pacemaker, leading to a phase shift in the circadian rhythm. The differential pattern of rhythm disturbance found in this study could be indicative of different processes involved in sleep disorders in the dementias.

Swedish forests are mostly used for timber harvesting and 96 % of this harvesting is made by clear cutting while only 4 % is effected through other methods such as single tree harvesting. All species are not affected by forestry to same magnitude. Some specifically generalists are not affected at all. Hence, this study, had its aim to find out vascular plant species that persist, disappear or colonize other species as a result of anthropogenic disturbances in different production forests, so as to determine not only if canopy openness affects the species distribution but also the magnitude of the effects. I examined 10 different forest localities during May and June 2008. Three of these localities were made up of clear cut forest plots, 3 with partially cut down forest plots and 4 with undisturbed production forest plots. Species composition and diversity were then compared between these plots. A total of 34 different species were found. Statistical Analysis was made on how well the species in the partially cut down forest plots fitted into the undisturbed forest group as well as comparing this results with results of how counterpart species in the clear cut forest plots fitted into the undisturbed forest groups. These results showed that there was no significant difference, ANOVA values of P = 0.839, 0.602 and 0.564 respectively among the species composition between the forest, partially cut down and clear cut forest groups between the forest, partially cut down and clear cut forest plots. However, among the 54 species found in all study plots, 11 were common between the forest and partially logged sites whereas only Carex sp in the clear cut forest was common to those in the forest plots implying that canopy openness did not affect the total species number but had an effect in species composition. Clear cutting seems to kill off everything but trees and generalists. Hence, resiliency of vegetation should be increased by management practices that ensure the maintenance of prior species.

Une des causes de handicap chez le patient victime d’un AVC sont les perturbations posturales à l’origine d’un plus grand risque de chute. A ce jour, bien qu’un trouble de la représentation spatiale semble être impliqué dans ces mécanismes d’action, ceux-ci ne sont pas encore totalement compris. L’objectif de cette thèse est d’étudier l’implication de la représentation spatiale dans les troubles posturaux suite à un AVC et plus spécifiquement dans l’asymétrie d’appui puis d’évaluer l’effet de stimulations proprioceptives par vibration des muscles du cou à la fois sur l’asymétrie d’appui et sur la représentation spatiale afin de mieux appréhender les mécanismes d’action de cette stimulation sensorielle. Nos travaux confirment la présence d’asymétrie d’appui en phase aiguë mais également persistante en phase chronique avec un déficit légèrement plus marqué pour les patients AVC droit. Les troubles de la représentation spatiale semblent être plus impliqués dans les mécanismes de ce comportement postural que le déficit moteur et/ou sensitif. Nos travaux vont dans le sens du rôle de l’hémisphère droit dans la représentation spatiale. Ces résultats pourraient expliquer l’asymétrie d’appui plus marqué dans le groupe de patients avec une lésion au niveau de l’hémisphère droit dû à un trouble de la représentation spatiale. Les stimulations sensorielles par vibration musculaire constituent un outil intéressant dans le domaine de la rééducation de par leur action à la fois sur la posture et la représentation spatiale. L’application de stimulations sensorielles de façon répétée réduit l’asymétrie d’appui dans le groupe de patients AVC droit chroniques à la fin du programme de 10 sessions avec un léger maintien à distance, suggérant l’intérêt d’appliquer ces stimulations en rééducation et, notamment, dans la prise en charge de patients avec un trouble de l’équilibre secondaire à un trouble de la représentation spatiale
One of the causes of disability in stroke patients is postural disturbances which increases the risk of falls. To date, even though a spatial representation disorder appears to be involved in these mechanisms of action, they are yet not fully understood. The objective of this thesis is to study the involvement of spatial representation in postural disorders following a stroke and more specifically in supporting asymmetry and then to evaluate the effect of proprioceptive stimuli by vibration of the neck muscles on both supporting asymmetry and spatial representation in order to better understand the mechanisms of action of this sensory stimulation. Our work confirms the presence of support asymmetry in the acute phase, but also persistent in the chronic phase with a slightly more pronounced deficit for patients with a right brain stroke. Disorders of spatial representation seem to be more involved in the mechanisms of action of this postural behavior rather than motor and/or sensory deficits. Our work supports the role of the right hemisphere in spatial representation; and these results could explain the more pronounced asymmetry of support in the group of patients with a lesion in the right hemisphere due to a spatial representation disorder. Sensory stimulation by muscle vibration is an interesting tool in the field of rehabilitation because of its action on both posture and spatial representation. The repeated application of sensory stimuli reduces the support asymmetry in the group of chronic right brain damage stroke patients at the end of the 10-sessions program, with a slight distance maintenance, which suggests the value of applying these stimuli in rehabilitation and particularly in the management of patients with a secondary balance disorder in a spatial representation disorder

Tese de doutoramento, Ciências e Tecnologias da Saúde (Desenvolvimento Social e Humano), Universidade de Lisboa, Faculdade de Medicina, 2013
In this thesis we investigated apathy secondary to stroke, both in acute and in post-acute phases. We aimed at studying apathy at 1-year after stroke and its relationship with apathy in acute stroke, demographic, pre-stroke predisposing conditions and clinical features (stroke type and location), post-stroke depression and cognitive impairment, functional outcome, and Quality of Life and Health. Apathy is a disturbance of motivation evidenced by low initiative, difficulties in starting, sustaining or finishing any goal-directed activity, low self-activation or self-initiated behaviour and/or emotional indifference. Caregivers often describe patients as presenting loss of initiative, emotional indifference and unconcern, which only became apparent after stroke. This disturbance is defined by the DSM-IV-TR clinical criteria as Personality Change Due to Stroke-Apathetic Type. Apathy may be mistaken as depression or as a detachment on caregivers to whom patients were emotionally attached previously. This state is not seen by the patient as a reason to complain to relatives or doctors, and patients accepted this new way of living and often do not report as problematic. To start our research on post-stroke apathy we performed a systematic review to better estimate its rate and relationship with associated factors, as well as to explore if apathy is associated with a poorer clinical outcome (Chapter 3: Apathy secondary to stroke: a systematic review and meta-analysis). A total of 19 different stroke samples were included for analysis. The frequency of apathetic patients ranged between 15.2 to 71.1%. Pooled rate of apathy secondary to stroke was 36.3% (95%CI 30.3 to 42.8%). In the acute phase the rate of apathy was 39.5%, and in the post-acute phase the rate was 34.3%. Apathy rate was significantly higher in any-stroke (first-ever or recurrence of stroke) studies (41.6%; I2=44.9%) compared with studies including only first-ever strokes. Apathetic patients are about 3 years older than non-apathetic patients. Apathy was a common condition in older persons and in particular in older cognitively impaired people and stroke is a risk factor for apathy in both. The rate of “pure” apathy (without concomitant depression) was twice as frequent as the rate of “pure” depression (without concomitant apathy). These two neuropsychiatric disturbances were not associated, in spite of the concomitance of both in one third of the samples of stroke patients. Apathetic patients were more frequently and severely depressed in comparison to non-apathetic patients. The rate of apathy secondary to stroke was similar for left and right-sided hemispheric stroke lesions and for ischemic and hemorrhagic stroke type. Finally, apathy secondary to stroke had a negative impact on clinical global outcome only if apathetic patients were first-ever stroke and were younger. The apparent discrepancy of our finding may be related to characteristics of apathy itself because apathetic patients may be less aware or report fewer complains about a loss of functionality. It also can be due to the fact that not all the original studies present a relationship between apathy and the factors. We performed a preliminary study aiming at describing the metric properties of the clinical-rated (AES-C) and self-rated (AES-S) versions of the Apathy Evaluation Scale (Chapter 4: Metric properties of the Portuguese version of the Apathy Evaluation Scale). This study was the baseline for the achievement of the other five goals proposed (Chapter 5: Post-Stroke apathy: An Exploratory longitudinal study), which depended on this one. The AES-C and the AES-S are validated for English language. The Apathy Evaluation Scale is useful to characterize and quantify apathy. We included 156 “healthy participants”, 40 healthy “elderly participants”, 21 patients with dementia, and 21 patients with depression, comprising a sample of 238 individuals. The AES-C (Cronbach α=.82; Split-half=.67) and the AES-S (Cronbach α=.81; Split-half=.60) showed good construct validity and high internal consistency. The items that loaded onto the analysis of principal components for the AES-C and AES-S were quite similar. The cut-off point of AES-C was dependent on the educational level (0-4 years of education= 38; 5-9 years=37; ≥10 years=30). The cut-off point of the AES-S was 39 points. The comparison among the four samples revealed that patients with dementia had higher scores in the AES-C. For the AES-S healthy participants scored themselves with the lowest mean scores. The Portuguese versions of the AES-C and of the AES-S were reliable and valid instruments to measure apathy in Portuguese speaking individuals. The first goal of our principal study aimed at describing the frequencies of post-stroke apathy at 1-year after stroke. Additionally, we aimed at finding out, which was the relationship between apathy in acute stroke and post-stroke apathy. (Chapter 5: Post-Stroke Apathy: An Exploratory Longitudinal Study). In the study on post-stroke clinical-rated apathy we identified 22.4% in acute stroke phase and 23.7% of post-stroke apathy at 1-year follow-up. In our multivariate model apathy in acute stroke (OR=3.8) was an independent factor for post-stroke apathy at 1-year follow-up. Apathy in acute stroke was a predictor of 41% of post-stroke apathy; two-fifths of the patients with acute apathy may still be apathetic at 1-year follow-up. We found that apathy in acute stroke increased the risk of post-stroke apathy in almost four-time fold. Nevertheless, 61% of the post-stroke apathy cases were identified at follow-up, which highlights for the importance of the evaluation of apathy at follow-up. The second goal aimed at analysing the relationship between post-stroke apathy and a specific acute stroke location (Chapter 5: Post-Stroke apathy: An Exploratory longitudinal study). No associations were found between post-stroke apathy and stroke location, but we found a trend of an association with hemispheric stroke location. Lesions in the cerebellum or at the brainstem are not involved in motivation disturbances and were not related to post-stroke apathy. In our systematic review there was no sufficient data to support conclusions, however one fact became apparent that older patients presenting left-sided stroke lesions had a significant higher rate of apathy (either acute or post-acute). The third goal of our principal study had the purpose to analyse the relationship between post-stroke apathy and post-stroke cognitive impairment (Chapter 5: Post-Stroke apathy: An Exploratory longitudinal study). We found that, at 1-year follow-up, post-stroke verbal abstract reasoning impairment was an independent risk factor for post-stroke apathy, increasing the risk of post-stroke apathy by seven-time fold. Apathetic patient’s thinking relies on a non-abstract process but instead on a concrete dimension. Abstract reasoning ability is an important prerequisite for the use of prior learning in new contexts or to the way in which prior learning affects new learning and performance. The improvement of abstract reasoning is important for patients who, due to brain lesion, have difficulties in their daily living activities. The fourth goal of our study aimed at making the analysis of the relationship between post-stroke apathy and post-stroke depression (Chapter 5: Post-Stroke apathy: An Exploratory longitudinal study). In our sample post-stroke apathy and depression were present in a quarter of our patients, but in three quarters the two clinical neuropsychiatric disturbances were independent one from the other. In our systematic review (Chapter 3: Apathy secondary to stroke: a systematic review and meta-analysis) apathetic patients were more severely depressed mostly in the acute phase of stroke and for younger patients. The fifth goal aimed at analysing the relationship between post-stroke apathy and late outcome (Chapter 5: Post-Stroke apathy: An Exploratory longitudinal study). We found a relationship between post-stroke apathy and bad functional outcome. Nevertheless, apathetic post-stroke patients did not report a loss in quality of life or in self-perception of health, when compared with non-apathetic post-stroke patients. In our systematic review (Chapter 3: Apathy secondary to stroke: a systematic review and meta-analysis) we did not confirm that apathetic patients had worse clinical global outcome, however there is a trend for patients with first-ever stroke and younger patients present poorer clinical global outcome.
Nesta tese investigámos a apatia secundária ao Acidente Vascular Cerebral (AVC), tanto durante a fase aguda como na fase pós-aguda do AVC (após AVC). Tivemos como objetivo o estudo da apatia ao 1º ano após o AVC e a relação desta com a presença de apatia na fase aguda do AVC, fatores demográficos, condições predisponentes prévias ao AVC e variáveis clínicas (tipo e localização do AVC), depressão e defeito cognitivo após AVC, estado funcional e Qualidade de Vida e perceção de saúde. A apatia é um distúrbio da motivação que se evidencia por baixa da capacidade de iniciativa, por dificuldades em iniciar, suster e finalizar uma atividade dirigida a um objetivo, por uma auto-ativação ou comportamento auto-iniciado baixo e/ou indiferença emocional. Os cuidadores frequentemente descrevem os seus pacientes como apresentando perda da iniciativa, indiferença emocional e despreocupação, apenas observáveis após o AVC. Esta perturbação pode ser clinicamente definida no DSM-IV-TR como uma Perturbação da Personalidade secundária ao AVC – Tipo Apático. A apatia pode ser confundida com depressão ou desapego aos cuidadores, aos quais o paciente esteve emocionalmente ligado. Este estado não é visto ou sentido pelo paciente como um estado que requeira preocupação e consequentemente como algo de que se queixar ao seu médico ou aos seus familiares. Os pacientes frequentemente aceitam esta nova forma de estar ou de viver e não a reportam como algo problemático. Para iniciar a nossa investigação sobre a apatia após o AVC fizemos uma revisão sistemática e recorremos à meta-análise. Pretendemos estimar a frequência da apatia secundária ao AVC e a relação desta com fatores associados, bem como explorar se a apatia estaria associada a um mau prognóstico clínico (Capítulo 3: Apathy secondary to stroke: a systematic review and meta-analysis). No total foram incluídas na análise sistemática 19 amostras de pacientes com AVC. A frequência de pacientes apáticos variou entre 15.2 e 71.1%. O global das frequências de apatia secundária ao AVC foi de 36.3% (IC 95% 30.3 a 42.8%). Especificamente na fase aguda do AVC a frequência de apatia foi de 39.5% e na fase após AVC a frequência foi de 34.3%. A frequência de apatia foi significativamente maior nos estudos que incluíam qualquer tipo de pacientes (incluindo 1º AVC e recorrência de AVC) (41.6%; I2=44.9%) comparativamente aos estudos incluindo apenas pacientes com 1º AVC. Os pacientes apáticos eram cerca de 3 anos mais velhos que os pacientes não apáticos. A apatia era uma condição comum em pacientes mais velhos e, em particular, em pacientes mais velhos com defeito cognitivo. O AVC é um fator de risco para o surgimento de apatia em qualquer destes. A frequência de apatia “pura” (sem depressão concomitante) foi o dobro da frequência de depressão “pura” (sem apatia concomitante). Estes dois distúrbios neuropsicológicos não estavam associados, apesar de cerca de um terço das amostras de pacientes com AVC apresentar ambos. Os pacientes apáticos eram mais frequente e severamente depressivos comparativamente aos pacientes não apáticos. A frequência de apatia secundária ao AVC foi similar em doentes com AVC do hemisfério direito e esquerdo, bem como para pacientes com AVC isquémico ou hemorrágico. Finalmente, a apatia secundária ao AVC teve um impacto negativo no estado clínico global final apenas em pacientes com 1º AVC e em pacientes mais jovens. A aparente discrepância entre os nossos dados obtidos através da meta-análise e os estudos originais pode estar relacionada com as características da própria apatia, porque os doentes apáticos podem reconhecer menos frequentemente e queixarem-se menos da perda da sua funcionalidade. Também pode dever-se ao facto de nem todos os estudos constatarem uma relação entre a apatia e os fatores estudados. Realizámos também um estudo preliminar que teve como objetivo descrever as propriedades métricas das versões clinica (AES-C) e de auto-avaliação (AES-S) da Escala de Avaliação da Apatia (Capítulo 4: Metric properties of the Portuguese version of the Apathy Evaluation Scale). Este objetivo foi o ponto de partida para atingirmos os outros cinco objetivos a que nos propusemos no estudo principal (Capítulo 5: Post-Stroke apathy: An Exploratory longitudinal study), os quais estavam dependentes deste. A AES-C e a AES-S estão validadas na versão original inglesa. A AES é utilizada para caracterizar e quantificar a apatia. Estudámos uma amostra de 156 “participantes saudáveis”, 40 “participantes idosos saudáveis” de um centro de dia, 21 pacientes com demência e 21 pacientes com depressão, perfazendo uma amostra total de 238 indivíduos. Estudámos o nível de fidelidade através do Alpha (α) de Cronbach e do método Split-half, bem como a validade de constructo através da análise dos componentes principais com rotação de Varimax. Na sua versão Portuguesa, tanto a AES-C (Cronbach α=.82; Split-half=.67) como a AES-S (Cronbach α=.81; Split-half=.60) apresentaram boa validade de constructo e uma boa consistência interna. Os itens incluídos na análise de principais componentes da AES-C e AES-S eram similares. O ponto de corte da AES-C esteve dependente do nível de educação (0-4 anos de educação= 38 pontos; 5-9 anos=37 pontos; ≥10 anos=30 pontos) e o ponto de corte da AES-S foi de 39 pontos. A comparação entre as quatro amostras revelou que os pacientes com demência apresentaram pontuações mais altas na AES-C. Relativamente à AES-S, os participantes saudáveis apresentaram as pontuações mais baixas. As versões portuguesas da AES-C e da AES-S mostraram ser instrumentos válidos para medir a apatia em sujeitos portugueses. O nosso estudo principal teve como primeiro objetivo descrever as frequências da apatia 1 ano após AVC. Adicionalmente, tivemos como objetivo descobrir qual a relação entre a apatia na fase aguda e a apatia após AVC (Capitulo 5: Post-Stroke Apathy: An Exploratory Longitudinal Study). Neste estudo, a apatia avaliada clinicamente foi identificada em 22.4% dos pacientes na fase aguda e em 23.7% na fase após AVC. No modelo estatístico multivariado, a apatia na fase aguda (OR=3.8) foi um fator independente para a apatia após AVC. A apatia na fase aguda foi um preditor de 41% dos casos de apatia após AVC; ou seja, dois quintos dos pacientes com apatia na fase aguda permaneceram apáticos ao 1 ano após AVC. Descobrimos que a apatia na fase aguda do AVC quase quadruplicava o risco de apatia após AVC. Não obstante, 61% dos casos com apatia após AVC foram apenas identificados durante o seguimento, o que denota a importância da avaliação da apatia nas consultas de seguimento. O segundo objetivo teve como propósito analisar a relação entre a apatia após AVC e uma lesão aguda específica originada pelo AVC (Capítulo 5: Post-Stroke apathy: An Exploratory longitudinal study). Não se encontraram associações entre a apatia após AVC e a localização da lesão em fase aguda do AVC. No entanto, encontrou-se uma tendência associativa relativamente à localização hemisférica da lesão. As lesões do cerebelo e do tronco não estavam envolvidas nos distúrbios da motivação nem estavam relacionadas com a apatia após AVC. Na revisão sistemática que realizámos não houve dados suficientes que permitissem suportar qualquer conclusão; contudo, realçou o facto de os pacientes mais velhos e com lesões lateralizadas à esquerda apresentarem frequências de apatia mais elevadas (tanto na fase aguda como após AVC). O terceiro objetivo do nosso estudo principal pretendia analisar a relação entre a apatia após AVC e o defeito cognitivo após AVC (Capítulo 5: Post-Stroke apathy: An Exploratory longitudinal study). Após 1 ano de seguimento, o défice do raciocínio abstrato verbal foi identificado como sendo um fator de risco independente para a apatia após AVC, incrementando o risco de apatia após AVC em sete vezes. O raciocínio dos pacientes apáticos baseia-se não num pensamento abstrato mas sim num pensamento concreto. A capacidade de raciocínio abstrato é um pré-requisito importante para que o sujeito utilize a aprendizagem prévia em novos contextos ou para que essa aprendizagem afete as novas aprendizagens e as novas realizações. A possibilidade de recuperar o raciocínio abstrato é importante para os pacientes que, devido a uma lesão cerebral, têm dificuldades nas atividades de vida diária. O quarto objetivo do nosso estudo principal tinha como propósito analisar a relação entre a apatia após AVC e a depressão após AVC (Capítulo 5: Post-Stroke apathy: An Exploratory longitudinal study). Na nossa amostra, a apatia após AVC e a depressão estavam presentes em um quarto dos pacientes com AVC. No entanto, em três quartos do grupo de pacientes os dois distúrbios neuropsiquiátricos eram independentes um do outro. Na nossa revisão sistemática (Capítulo 3: Apathy secondary to stroke: a systematic review and meta-analysis) os pacientes apáticos estavam mais severamente deprimidos, particularmente na fase aguda do AVC e os pacientes mais novos. O quinto objetivo do nosso estudo pretendeu analisar a relação entre a apatia após AVC e a funcionalidade clínica (Capítulo 5: Post-Stroke apathy: An Exploratory longitudinal study). No nosso estudo encontrámos uma relação entra a apatia após AVC e uma má funcionalidade. Contudo, os pacientes apresentando apatia após AVC não revelaram ter perdido nem Qualidade de Vida nem saúde em comparação com pacientes sem apatia. Na nossa revisão sistemática (Capítulo 3: Apathy secondary to stroke: a systematic review and meta-analysis) não confirmámos que os pacientes apáticos apresentassem pior funcionalidade clínica. No entanto, identificámos uma tendência de associação entre a perda de funcionalidade clínica e o facto de serem pacientes com primeiro AVC ou pacientes mais novos.
Fundação para a Ciência e a Tecnologia (FCT, SFRH/BD/22282/2005)

Vascular cognitive impairment (VCI) refers to the spectrum of cognitive disturbances that result from cerebrovascular brain injury. Cerebrovascular disease is associated with multiple underlying pathologies. Risk factors, clinical features, and treatment options overlap with those associated with Alzheimer’s disease, another common cause of cognitive decline. The complexity of vascular cognitive impairment and, notably, the interplay between clinical, pathologic, genetic, and biomarker characteristics of VCI and Alzheimer’s disease are discussed. The chapter places an emphasis on vascular cognitive impairment resulting from disease affecting small vessels, in contrast to that due to disease involving large vessels, in an effort to focus on a large body of evolving work and ongoing attempts at improving understanding of this complex entity.

Chronic kidney disease is associated with the inability to control normal mineral homeostasis, resulting in abnormalities in serum levels of calcium, phosphorus, parathyroid hormone, fibroblast growth factor 23 (FGF23) and vitamin D metabolism. These disturbances lead to the development of secondary hyperparathyroidism, skeletal abnormalities, vascular calcifications, and other systemic manifestations. Traditionally, mineral and bone abnormalities seen in chronic kidney disease were included in the term ‘renal osteodystrophy’. More recently, the term chronic kidney disease-mineral and bone disorder was introduced to define the biochemical abnormalities of phosphorus, parathyroid hormone, FGF23, calcium, or vitamin D metabolism, abnormalities in bone remodelling and mineralization, and vascular or other soft tissue calcifications.

Delirium is the most common acute cognitive disorder seen in critically ill patients in the cardiovascular intensive care unit. It is defined as a disturbance of consciousness and cognition that develops suddenly and fluctuates over time. Delirious patients can become hyperactive, hypoactive, or both. The occurrence of delirium during hospitalization is associated with increased in-hospital and long-term morbidity and mortality. The cause of delirium is multifactorial and may include imbalances in neurotransmitters, inflammatory mediators, metabolic disturbances, impaired sleep, and the use of sedatives and analgesics. Patients with advanced age, dementia, chronic illness, extensive vascular disease, and low cardiac output are at particular risk of developing delirium. Specialized bedside assessment tools are now available to rapidly diagnose delirium, even in mechanically ventilated patients. Increased awareness of delirium risk factors, in addition to non-pharmacological and pharmacological treatments for delirium, can be effective in reducing the incidence of delirium in cardiac patients and in minimizing adverse outcomes, once delirium occurs.

Delirium is the most common acute cognitive disorder seen in critically ill patients in the cardiovascular intensive care unit. It is defined as a disturbance of consciousness and cognition that develops suddenly and fluctuates over time. Delirious patients can become hyperactive, hypoactive, or both. The occurrence of delirium during hospitalization is associated with increased in-hospital and long-term morbidity and mortality. The cause of delirium is multifactorial and may include imbalances in neurotransmitters, inflammatory mediators, metabolic disturbances, impaired sleep, and the use of sedatives and analgesics. Patients with advanced age, dementia, chronic illness, extensive vascular disease, and low cardiac output are at particular risk of developing delirium. Specialized bedside assessment tools are now available to rapidly diagnose delirium, even in mechanically ventilated patients. Increased awareness of delirium risk factors, in addition to non-pharmacological and pharmacological treatments for delirium, can be effective in reducing the incidence of delirium in cardiac patients and in minimizing adverse outcomes, once delirium occurs.

Hypertension affects multiple groups of patients characterized by different clinical presentations and a spectrum of potential causes. The pathophysiology is complex and multifactorial. Although most patients are labelled ‘essential hypertension’, multiple mechanisms are involved in blood pressure regulation. Factors that influence blood pressure homeostasis include endothelial function, the renin-angiotensin system, and the sympathetic nervous system. In elderly patients, hypertension is common as the vascular system and arterial stiffness also contribute. Other important factors include inflammatory processes as part of systemic diseases, including atherosclerosis,which may contribute to renal and vascular injury. Hypertension is also associated with metabolic disturbances including dyslipidaemia that manifests in obese patients who also have insulin resistance. These different pathways all represent potential targets for treatment, but also increase the challenge of multimodal pathophysiology.

The brain is protected by the cranial skeleton. Within the intracranial compartment are also cerebrospinal fluid, CSF, and the blood contained within the brain vessels. These intracranial components are in dynamic equilibrium due to the pulsations of the heart and the respiratory regulated return of venous blood from the brain. Normally the mean arterial blood pressure, systemic venous pressure, and brain volume are regulated to maintain physiological values for intracranial pressure, ICP. There are a range of very common disorders such as stroke, and much less common, such as idiopathic intracranial hypertension, that are associated with major disturbances of intracranial pressure dynamics. In some of these the contribution to pathophysiology is relatively minor whereas in others it may be substantial and be a major contributory factor to morbidity or even death.Intracranial pressure can be disordered because of brain oedema, disturbances in CSF flow, mass lesions, and vascular engorgement of the brain. Each of these may have variable causes and there may be interactions between mechanisms. In this chapter the normal regulation of intracranial pressure is outlined and some common disease states in clinical neurological practice that are characterized by either primary or secondary problems in intracranial pressure dynamics described.

This chapter reviews bladder disturbances in non-traumatic neurological conditions and provides an approach to its evaluation and management. The pattern of bladder dysfunction depends upon the level of neurological localisation and accordingly, lesions can be suprapontine, infrapontine/suprasacral (spinal), or infrasacral. The importance of the frontal lobes for bladder control has been confirmed and vascular disease or tumour can result in incontinence. There is better understanding about the very different urological profile of the two sometimes confused conditions, multiple system atrophy and Parkinson’s disease. Guidelines for the management of lower urinary tract dysfunction in multiple sclerosis are reviewed. Lower urinary tract (LUT) dysfunction is common in neurological disease and its importance to patient health and quality of life is now widely recognized.

After control of the primary process causing acute neurological injury, further control of secondary injury pathways can be achieved by manipulating brain temperature, and achieving biochemical and metabolic homeostasis. Surgical techniques are routinely used to remove blood or trapped cerebrospinal fluid, control mass effect, or repair unstable vascular abnormalities. Therapeutic temperature management to a defined target can be achieved and maintained using cold fluids, ice packs, body surface cooling pads, and surface and intravascular devices with servo (feedback) mechanisms. Successful temperature management requires attentive surveillance and control of shivering and other potential complications, such as bleeding, infection, cardiac arrhythmias, and electrolyte and metabolic disturbances. Extremes of oxygenation and ventilation are associated with worse long-term functional outcomes, and should be avoided.

The liver may be involved in systemic diseases that primarily affect other organs. In most cases, the systemic disease should be treated effectively first. Circulatory disturbances can cause liver dysfunction by ischaemia (due to arterial hypoperfusion) and hepatic venous congestion. The liver is a key organ in sepsis, both as source of inflammatory mediators and as a victim of the inflammatory response. An oncological process may affect hepatic function in a number of ways. For example, tumours in and around the liver can affect function by directly reducing the volume of healthy, functioning tissue or by causing biliary obstruction, and portal venous infiltration or hypercoagulability may compromise the liver’s vascular supply. This chapter discusses the liver in systemic disease, including sections on etiology, symptoms, demographics, complications, diagnosis, and treatment.

After its introduction, continuous renal replacement therapy (CRRT) has found widespread acceptance amongst physicians taking care of critically ill patients. Various modalities (haemofiltration, haemodialysis, haemodiafiltration) are used. As for all types of renal replacement therapy, a good functioning vascular access is an absolute requirement. Whether CRRT is to be preferred over intermittent haemodialysis remains a matter of debate, but haemodynamic instability and risk of cerebral oedema are generally considered indications for CRRT. Whereas under-dosing should certainly be avoided, increasing the dose over an actually delivered effluent flow of 20–25 mL/kg/hour does not appear to improve outcome.One of the major drawbacks of CRRT is the requirement for continuous anticoagulation. Citrate anticoagulation is gaining popularity and represents a valuable alternative, especially in patients with bleeding risk. Other potential complications of CRRT include thermal, nutrient, and drug losses, and acid–base and electrolyte disturbances.

The endothelium is an organ with a key role in the maintenance of cardiovascular health through the regulation of vascular tone, vascular resistance, blood flow, and arterial pressure. These functions are related with the synthesis and release of vasoactive molecules, mainly vasodilators like nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF). Both factors are released and diffused from endothelial cells to the smooth muscle cells, where there is a subsequent activation of signaling pathways that finally decrease the intracellular calcium to induce the vascular relaxation. The study of the molecular mechanisms that underlie the endothelial function still is in development, but from the evidence obtained from the endothelial cells in vitro studies are possible to partially describe the pathways to regulate the physiological endothelial function and the disturbances in pathological conditions. In this mini-review, we describe the main mechanisms for NO synthesis and the role of potassium channels related with EDHF. We include schemes and graphical summaries for better understanding of the molecular regulation of vascular tone in the human cardiovascular system.

• Primary hyperlipidaemias are autosomal dominant or recessive inherited disturbances in lipid metabolism, which become manifest either from early childhood or later in life. • Clinical manifestations are premature ischaemic vascular disease, xanthomatosis and other lipid depositions in the body, and acute pancreatitis. • The molecular defect is explained by mutations in genes, which encode proteins that play a major role in the formation, secretion, transport, or uptake of lipoproteins. • The most common forms of primary dyslipidaemias are multifactorial heterogeneous disorders with several genetic, metabolic, and environmental factors interacting and contributing to the clinical phenotype. • Family investigation is usually crucial for proper diagnosis and case finding of persons at risk for vascular disease.

End-stage renal disease (ESRD) occurs as a result of any renal injury that chronically decreases renal excretory and regulatory function. ESRD patients are most commonly treated with hemodialysis (HD) to manage their renal failure while awaiting kidney transplant. Current practices for maintenance of HD vascular access consist of arteriovenous fistulas (AVFs) or grafts (AVGs), which are both fraught with problems that compromise the patency and use of these surgically created shunts. The major cause of shunt failure is thrombosis caused by occlusion of the outflow venous anastomosis and draining vein. Intimal hyperplasia (IH), which consists of the thickening of the innermost layer of the vessel wall, is the initial pathological event leading to shunt stenosis/thrombosis and has been associated with the presence of flow disturbances and abnormal wall shear stress (WSS) at the graft-vein anastomosis. Therefore, the improvement of HD via the enhancement of vascular access patency requires the development of a novel vascular access technology preserving the normal hemodynamics of the native vein.

In the cardiovascular system, the flow of blood within the complex vascular network creates hemodynamic shear forces experienced by cells. Situated between the circulating blood and the bulk vascular tissue, the endothelium is a cell monolayer acting as a barrier that protects the underlying arterial tissue. Shear forces have been seen to interact with and regulate endothelial cells through mechanotransduction induced cytoskeletal changes within the cell [1]. Shear forces can be beneficial in cases of laminar flow, which are thought to be atheroprotective by aligning and organizing endothelial cells [2]. However, disturbances to a smooth flow field, caused by vessel bifurcations or obstructions like an implanted stent or a bulging atherosclerotic lesion, can cause recirculation zones to form downstream. In these flow regions, detrimental monolayer remodeling occurs which breaks down the endothelial barrier function [3]. Biochemically, it has been seen that shear forces drive signaling cascades in the Rho/Rac pathways that cascade into morphological changes in the cytoskeleton [4].

The in vivo dynamics of thrombus formation have not been extensively studied, mainly due to technical limitations. We assessed the dynamics and localization of platelet deposition on a prosthetic vascular graft for the first 24 hours after implantation in swine, with continuous monitoring during the initial 6 hours, and the effect of heparin. Polytetrafluoro-ethylene (PTFE) grafts (5cm. L × 0.5 cm. ID) were inplanted in one of the common carotids of 13 normal pigs; 8 received iv heparin (150uAg) perioperatively. 111 In-labelled autologous platelets were injected 5 min before reperfusion of the graft. From 10 min to 24 hrs after unclamping the vessel sequential gamma camera images of the neck were taken and stored in an on-line computer. Pinpoint analysis of the platelet deposition was performed by creating seven regions of interest of 5 × 5 pixels over both graft and contralateral carotid territories. We obtained the ratio of the 111 In-activity in each region of the graft, including both anastomoses, with respect to its contralateral homologous region. The ratios differed along the graft in both groups of animals, with maximal values at the anastomosis. Peak ratios were reached within 1 to 3 hrs, and were significatively lower in heparinized pigs (anastomosis: 1.95±0.36; graft: 1.3±0.66) than in rion-heparinized-pigs (anastomosis: 3.23±0.66; graft: 2.16±0.41; p<0.05). Heparinized pigs showed a progressive decrease of the ratios up to 24 hrs. In contrast, platelet deposition in non-heparinized-pigs continued up to 6 hrs. Patency at 24 hrs was 88% in heparinized-pigs versus 20% in non-heparinized-pigs. We conclude that computer assisted pinpoint analysis of platelet deposition may help to a better understanding of the thrombotic process differentiating platelet-graft interaction from platelet anastomosis interaction. The deposition of platelets and graft patency is strongly influenced by the stabilizing effect of procoagulant moieties, and the presence of the anastomosis (release of vessel wall procoagulant and platelet activating products and induction of blood flow disturbances) induces localized activation and deposition of platelets.

We have reported cerebrovascular injuries induced by platelet aggregation in vivo. Appearance of vacuoles in endothelial cells and eventual deendothelialization are characteristic in large cerebral arteries (Stroke, 16:245, 1985). Minor changes are observed in brain capillaries, but disturbances of blood-brain barrier (BBB) are seen. To analyse changes in BBB, enzymatic activities in capillary endothelial cells before and after ADP-induced platelet aggregation in vivo were investigated.80 mg/kg of ADP was injected through a catheter into the right internal carotid artery of 32 rabbits. One hr later, right and left cortexes freed from pial membranes were homogenized and microvessels were isolated using discontinuous sucrose gradient ultracentrifugation. Purity of microvessel fraction was ascertained microscopically. The follwing enzymatic activities in these samples were measured.; cytochrome C oxydase (CCO), monoamine oxidase (MAO), p-nitrophenyl-phosphatase transferase (pNPPase, K-dependent component of Na, K-ATPase), gamma-glutamyl transferase (GT) and adenylate cyclase (AC). The enzymatic activities did not change after a vehicle-injection and did not show any differences between capillaries of both the cortexes before the ADP-injection. One hr after the ADP, GT and CCO activities decreased significantly in the capillaries of injection side. MAO activity also reduced without significance. The other enzymes did not show significant changes in their activities. Although pNPPase and AC which are associated with inner surface of plasma membrane were preserved well, activity of GT which is associated with outer portion of the membrane decreased significantly. It suggests superficial luminal injury and that plasma membrane might be affected from the side of vascular lumen. Reduced CCO activity suggests that disturbance in BBB is probably related to the increase in vesicular transportation and/or energy failure. Reduction of MAO activity indicates that damages to mitochondria exist in the capillaries. Cerebral blood vessels are prone to damage by released substances from activated platelet in vivo.

The initiation and progression of vessel wall pathologies have been linked to disturbances of blood flow and altered wall shear stress. The development of computational techniques in fluid dynamics, together with the increasing performances of hardware and software allow to routinely solve problems on a virtual environment, helping to understand the role of biomechanics factors in the healthy and diseased cardiovascular system and to reveal the interplay of biology and local fluid dynamics nearly intractable in the past, opening to detailed investigation of parameters affecting disease progression. One of the major difficulties encountered when wishing to model accurately the cardiovascular system is that the flow dynamics of the blood in a specific vascular district is strictly related to the global systemic dynamics. The multiscale modelling approach for the description of blood flow into vessels consists in coupling a detailed model of the district of interest in the framework of a synthetic description of the surrounding areas of the vascular net [1]. In the present work, we aim at evaluating the effect of boundary conditions on wall shear stress (WSS) related vessel wall indexes and on bulk flow topology inside a carotid bifurcation. To do it, we coupled an image-based 3D model of carotid bifurcation (local computational domain), with a lumped parameters (0D) model (global domain) which allows for physiological mimicking of the haemodynamics at the boundaries of the 3D carotid bifurcation model here investigated. Two WSS based blood-vessel wall interaction descriptors, the Time Averaged WSS (TAWSS), and the Oscillating Shear Index (OSI) were considered. A specific Lagrangian-based “bulk” blood flow descriptor, the Helical Flow Index (HFI) [2], was calculated in order to get a “measure” of the helical structure in the blood flow. In a first analysis the effects of the coupled 0D models on the 3D model are evaluated. The results obtained from the multiscale simulation are compared with the results of simulations performed using the same 3D model, but imposing a flow rate at internal carotid (ICA) outlet section equal to the maximum (60%) and the minimum (50%) flow division obtained out from ICA in the multiscale model simulation (the presence of the coupled 0D model gives variable internal/external flow division ratio during the cardiac cycle), and a stress free condition on the external carotid (ECA).

Research has been conducted by the authors with the objective to produce a computational model that will clearly display the coupled nature of the hemodynamics/fluid mechanics of blood flow and atherosclerotic plaque growth in the human carotid artery. The motivation for this investigation is the serious nature of atherosclerosis. Atherosclerosis is an inflammatory disease, which occurs in medium and large size arteries. Among the many effects stemming from the disease are heart attack, stroke, ischemia, and peripheral vascular disease. In healthy arteries, the collagen and elastin allow the artery to expand and contract with blood flow. This function enables the artery to maintain constant wall shear stress [1]. Plaque existence in the arterial wall results in decreased ductility of the wall, which inhibits the wall from maintaining constant shear stress. Plaque formations along the arterial wall then protrude into the artery, disturbing the blood flow. Characteristics of the fluid flow in the artery are also altered due to the presence of a plaque. Areas of low shear stress and recirculation move downstream from the plaque. These disturbances act not only to further the plaque formation at the site, but also to make the wall around the plaque formation more prone to lesions that could lead to new plaque initiation. Complex characteristics of the blood flow give areas of an artery such as bends and bifurcations a predisposition for the disease, whereas plaques affect blood flow, creating flow patterns that promote new plaque initiation. This interdependency makes atherosclerosis a very serious disease and one which is of great importance in research.

Red blood cell (RBC) filtration in platelet rich plasma (PRP) and platelet poor plasma (PPP) was equally decreased (p < 0.0001) in 120 patients with acute myocardial infarction (AMI) as compared to a control group. In a double-blind experiment 2 groups of 30 patients with AMI received an acute oral dose of 60 mg of ketanserin, a serotonin (5-HT) antagonist at 5-HT2-receptors, or placebo. Ketanserin treatment improved RBC filtration in PRP with an average increase of 30%. A similar experiment using PPP showed a significant increase of 10%. Filtration of plasma improved after ketanserin treatment in PRP, but not in PPP. Cross-exchange experiments showed the ketanserin-induced improvement of RBC filtration in PRP and PPP to be also plasmadependent. 5-HT in vitro at 10−9M deteriorated RBC filtration in PPP (p < 0.05), and ketanserin in vitro at 10−7M counteracted this phenomenon (p < 0.001). Finally we found that the effect of a subacute treatment with ketanserin on the filtration of RBC Suspensions, enriched with a constant amount of white blood cells (WBC), was more pronounced than on control RBC suspensions of patients with AMI.These results indicate that the impaired RBC filtration, reported in vascular diseases may be dependent on a subtle interaction between platelets, WBC, RBC and plasma. Treatment with ketanserin is capable to interrupt this vicious circle of rheological disturbances at different levels, first of all, by improving RBC deformability, but also by counteracting the platelet mediated effects on RBC and by favourably influencing the physical properties of WBC and so preventing clogging phenomena. Serotonin probably plays a pivotal role in these cascade of events and therapy with ketanserin might be of clinical value in diseases where microcirculatory flow is compromised.

Although the use of endovascular stents has significantly reduced the incidence of restenosis following balloon angioplasty, restenosis rates remain unacceptably high (20–35% of all angioplasty procedures [1]). Placement of a stent within an arterial segment locally injures vascular endothelium thereby stimulating thrombotic responses that contribute to the development of in-stent restenosis. Recent research suggests that the local fluid mechanical environment in the vicinity of a stent impacts the rate of vessel re-endothelialization following stent-induced injury [2]. This is supported by in vitro data demonstrating that endothelial repair after injury is sensitive to fluid mechanical forces [3]. Recent in vivo data suggest that in-stent restenosis preferentially develops in arterial regions exposed to low and/or oscillatory shear stress [1]. Therefore, it is essential to establish the detailed flow environment in the vicinity of a stent and to investigate the impact of this environment on EC function.

Atherosclerotic lesions tend to develop in regions where there are separations from unidirectional laminar blood flow, typically near branches, bifurcations, regions of arterial narrowing, and curvatures in the arteries (1, 2). Obviously, homodynamic forces play a key role in atherosclerosis. Studies also indicate that vascular endothelium function disturbance, especially impairment of endothelium dependent vasodilation, is involved (3). Shear stress affects endothelial cells in many ways, such as cytoskeletal rearrangement, decrease of intracellular pH, release of PGI2 and some growth factors (PDGF, FGF, ECGF, TGF-b, etc), activation of IP3 and mitogen-activated protein kinases, and the significant increase in the production of nitric oxide (1,2,4,5). As an important function factor of vascular endothelial cells, nitric oxide (NO) is closely related to the endothelial dysfunction and atherosclerosis (6). Endothelial derived nitric oxide involves in many events in the vasculature, including vasodilation, inhibition of platelet aggregation, adhesion molecule expression, and vascular smooth muscle proliferation, which are directly or indirectly related to atherosclerosis. Endothelial cells release NO more potently in response to increased shear stress than to agonists that raise intracellular free calcium concentration [Ca2+]i. Studies have indicated that NO production increases with a calcium/CaM dependent manner in the first few minutes after exposed to shear stress, followed by a sustained NO production that occurs more than 30min which is Ca2+ independent (7). The activation of eNOS by shear stress, which modulated by Ca/CaM, G protein, tyrosine kinase phosphorylation and eNOS gene expression, is responsible for the increase of NO production (8). However, the contribution of extracellular calcium to the production of NO is somewhat contradictory.

Compliance mismatch between a host artery and a vascular graft causes hemodynamic disturbance and stress concentration, which may lead to thrombus formation at an early stage and to neointimal hyperplasisa near the anastomosis at a later stage [1]. To optimal design artery substitutes, the requirements of geometric and compliance matching at mean blood pressure must be determined and used to guide the fabrication of the unloaded conduit with proper diameter and wall thickness. Given the range and complexity of structural behaviors that can be produced by independently varying structural properties of individual layers (fiber type, density, orientation and layer thickness), a sophisticated computational model is required to determine these conduit design parameters. In this paper, a novel nearly incompressible structural model was formulated and implemented into the commercial finite element code ABAQUS (Pawtucket, RI) for finite element artery inflation simulations. The profound artery compliance changes due to variations of fiber properties, the nearly incompressibility control parameter D, and different properties of intima-media and adventitia were investigated.