Made available in DSpace on 2016-07-18T17:53:09Z (GMT). No. of bitstreams: 1 beth[1].pdf: 1005574 bytes, checksum: 2fa927c95f66ff65dd7b52a8dbeedd7a (MD5) Previous issue date: 2012-03-26 / This study aimed to evaluate the efficacy of dobutamine comparatively with electroacupuncture and sham treatment to reversion of isoflurano-induced hypotension in equine. Six adult horses were evaluated using a crossover design with at least 15 days between treatments. All the horses were medicated with xylazine (0.5mg kg-1) by intravenous administration (iv). Guaifenesin (100mg/kg iv) and thiopental (5mg kg-1 iv) were administered, following the inhalation anesthesia with isoflurane. The horses were positionated in left lateral recumbency and they were maintained in mechanical ventilation. After anesthesia was established, the isoflurane concentration was raised until mean blood pressure was maintained between 40 to 45mmHg. After that, the animals were treated with a constant rate of 1.5mg kg -1min-1 intravenously dobutamine (DOB), electroacupunture to PC6 acupoint (EA) and sham treatment (Sham). All the treatments were maintained for 60 minutes. Heart rate, cardiac rhythms, median arterial blood pressure, rectal temperature, arterial blood gases, creatine kinase (CK), aspartate transaminase (AST), recovery time and quality of recovery were investigated. The mean blood pressure increased 50%, 36.5% and 7.5%% in DOB, EA and Sham treatment, respectively. Higher values were observed in the DOB treatment when compared with Sham treatment at 10, 20, 30 and 40 minutes and at 20 minutes when compared with EA treatment. Heart rate, blood gases, CK, AST, recovery time and quality of recovery did not differ among the treatments. It was concluded that the dobutamine treatment was more effective than electroacupuncture and Sham tretament for the reversion of isoflurane induced hypotension in horses. / Este estudo objetivou avaliar a eficiência do tratamento da hipotensão arterial induzida pelo isofluorano em equinos, com dobutamina comparativamente à aplicação de estímulo elétrico no acuponto pericárdio 6 (PC6) e em ponto falso de acupuntura. Foram avaliados seis cavalos adultos, saudáveis, provenientes do Hospital Veterinário da Unoeste. Os mesmos animais foram avaliados nos três tratamentos, com intervalo de 15 dias entre cada experimento. A medicação pré-anestésica foi feita com xilazina (0,5mg kg-1) por via intravenosa (iv). A indução anestésica foi realizada com éter gliceril guaiacol (100mg kg-1 iv, 10%) em associação ao tiopental sódico (5mg kg-1 iv), com posterior manutenção em anestesia geral inalatória com isofluorano, em ventilação mecânica. Após a estabilização da anestesia foi induzida a hipotensão arterial, mediante o incremento da concentração de isofluorano, até a obtenção de pressão arterial média (PAM) entre 40 a 45 mmHg. A partir do estabelecimento da hipotensão, os animais foram submetidos a um dos tratamentos: DOB: dobutamina (1,5µg kg-1 min-1) em infusão contínua iv; EA: aplicação de estímulo elétrico no acuponto PC6 bilateralmente; Sham: aplicação de estímulo elétrico em ponto falso de acupuntura. Todos os tratamentos foram mantidos durante 60 minutos. Foram mensurados: frequência cardíaca (FC) e ritmo cardíaco, pressão arterial média (PAM), temperatura retal (T), fração inspirada e expirada de isofluorano (ETiso), concentração final expirada de dióxido de carbono (ETCO2) e variáveis hemogasométricas (PaO2, PaCO2, pH, HCO3-1), concentração sérica de aspartato aminotransferase (AST) e creatina fosfoquinase (CK), tempo e qualidade da recuperação pós-anestésica. Houve incremento na PAM de 50%, 36,6% e 7,5% nos grupos DOB, EA e Sham, respectivamente. Valores superiores de PAM foram observados no tratamento DOB em relação ao tratamento Sham aos 10, 20, 30 e 40 minutos e aos 20 minutos em relação ao tratamento EA. A FC, as variáveis hemogasométricas, as enzimas CK e AST, o tempo e a qualidade de recuperação pós-anestésica não diferiram entre os grupos. Concluí-se que o tratamento com dobutamina foi mais efetivo para reversão de hipotensão em cavalos sob anestesia inalatória quando comparado ao estímulo elétrico do acuponto PC6 ou ponto falso de acupuntura.

The ability of an individual to withstand elevated head-to-toe gravitoinertial (+Gz) forces is determined by the capacity of their body to maintain sufficient head-level arterial pressure. Recent studies have shown a relationship between resting blood-vessel stiffness and an individual’s +Gz-tolerance, although the mechanisms behind this relationship are unclear. The aim of this project is to determine whether or not +Gz-tolerance is affected by a change inresting vasomotor tone. To evaluate this relationship, seven participants were asked to complete a +Gz-tolerance protocol using a human-use centrifugeon two different occasions. On both visits, gradual onset rate (0.1 G.s−1)and rapid onset rate (3.5 G.s−1) tests were done to evaluate the participants+Gz-tolerance. On one of the two visits, prior to the +Gz-tolerance testing,participants performed a 20-min cycle intervention to induce postexercisehypotension, with the aim of temporarily reducing participants’ resting bloodpressure and vasomotor tone. The cycling intervention was successful atinducing postexercise hypotension, as mean arterial pressure was significantlylower on the cycling visit (P<0.05). +Gz-tolerance was significantly lower(P<0.05) on the cycling visit compared with the non-cycling visit for both theGOR and ROR tests (absolute difference of 0.5 G and 0.25 G, respectively).The effect of the type of test on +Gz-tolerance was not influenced by the effectof the cycling intervention (P>0.05). Being the most documented mechanismlinked to postexercise hypotension, sustained vasodilation was assumed tohave occurred. This would have increased distensibility of the affected vessels,explaining the decrease in +Gz-tolerance. The decrease in +Gz-tolerance wassimilar for both tests, indicating that the baroreflex was not affected by thecycling intervention. Assuming that vasodilation occurred, this study showedthat a decrease in resting vasomotor tone decreased +Gz-tolerance, indicatingthe importance of this variable in the relationship between resting blood-vesselstiffness and an individual’s +Gz-tolerance.

Endomorphin 1 (10, 30, 100 nmol/kg) administered intravenously (i.v.) to urethane-anesthetized rats consistently and dose-dependently lowered heart rate (HR) and mean arterial pressure (MAP); the decrease in blood pressure recovered faster as compared to the HR. The effects of endomorphin 2 were qualitatively similar. Naloxone (2 mg/kg, i.v.) completely antagonized the bradycardia and hypotension caused by endomorphin 1. Pretreatment of the rats with atropine methylnitrate, atropine sulfate (2 mg/kg, i.v.) or bilateral vagotomy nearly abolished the bradycardia and attenuated the hypotensive effect of endomorphin 1. Our studies suggest that the bradycardia effect following systemic administration of the new opioid peptide may be explained by activation of vagal afferents and the hypotensive effect may be secondary to a reduction of cardiac output and/or a direct vasodilation.

I detta projekt har tiden för hur länge en patient befinner sig i hypotension samt hypotensionsdosen beräknats. Tiden i hypotension har beräknats med hjälp av episoder i över en minut och hypotensionsdosen har kalkylerats som integralen mellan hypotensionsgränsen 65 mmHg och den estimerade medelartärtryckskurvan (MAP-kurvan). Flera metoder användes, såsom klassificering av extrempunkter i rådata och kurvanpassning genom interpolation, vilket gav varierande och olika goda resultat. Detta framförallt beroende på hur datan behandlades med olika filter, till exempel så kallat “smoothing”-filter samt medianfilter. / In this project the time of how long a person is in hypotension and the hypotension exposure have been calculated. The time was calculated using episodes longer than one minute and the hypotension exposure has been calculated as the integral between the hypotension limit 65 mmHg and the estimated mean arterial pressure curve (MAP-curve). Several methods were used, such as classification of extreme values in raw data and curve fitting through interpolation, which gave diverse results and of varied accuracy. This primarily because of which filter that was used, for example smoothing and median filters.

Bakgrund: Andelen äldre över 60 år ökar och förväntas öka ytterligare framöver. Kognitiv svikt är en av de vanligaste åkommorna samt ett hälsoproblem över hela världen. En viktig riskfaktor för kognitiv svikt är åldrande. Ett annat tillstånd hos äldre som lätt förbises är ortostatisk hypotension (OH). Det finns studier som påvisar samband mellan OH och kognitiv svikt, likväl studier som inte påvisar något samband, vilket gör att det råder delade meningar. Ytterligare kunskap behövs för att stärka det vetenskapliga underlaget till distriktssköterskans hälsofrämjande arbete när det gäller patientutbildning och egenvårdsråd. Syfte: Syftet med studien var att undersöka om ortostatisk hypotension har ett samband med kognitiv svikt hos yngre äldre för att bidra med vetenskapligt underlag till distriktssköterskans hälsofrämjande arbete. Metod: Designen var en kvantitativ studie i samarbete med Swedish National Study on Aging and Care – Blekinge. Urvalet inkluderade yngre äldre (60-78år). Variabler som kön, ålder, utbildning, blodtrycksvärden samt resultat på Mini-Mental State Examination (MMSE) valdes ut. Analysen gjordes i statistikprogrammet SPSS och började med deskriptiv statistik. För att se signifikant skillnad genomfördes Mann-Whitney U-test och Chi-2. Till sist utfördes en logistisk regression för att undersöka vad som påverkade den kognitiva förmågan mest. Resultat: Hos yngre äldre påvisades ingen statistisk signifikans när det gäller sambandet mellan OH och kognitiv svikt. Däremot sågs en tendens som pekade på att av de som har kognitiv svikt så var det fler som hade OH. 72-åringarna hade lägst medelvärde på MMSE. Kvinnor hade i högre utsträckning både kognitiv svikt och låg utbildning än män. Lågutbildning var en riskfaktor för kognitiv svikt. Det sågs en markant ökning av OH där 14% av 60-åringarna hade OH och 36,7% av 72-åringarna. Generellt hade män i högre utsträckning OH än kvinnor.  Slutsats: Inget samband påvisades mellan OH och kognitiv svikt, däremot sågs en visuellt synlig skillnad i alla grupper utom 60 år. Prevalensen av OH ökade efter 60 år. Låg utbildningsnivå var en riskfaktor för kognitiv svikt. Genom ökad kunskap kan distriktssköterskan ge egenvårdsråd och säker hälsovägledning till patienter och närstående för att främja hälsan hos äldre individer

Introduction - Pure autonomic failure is a rare disorder characterized by orthostatic hypotension, absence of a compensatory rise in heart rate, and abnormal autonomic functions. In most cases, supine hypertension is seen coupled with orthostatic hypotension, making the management of these patients a big challenge. We present the case of a 74-year-old gentleman, who presented to the ED with altered mental status for a day; weakness, and falls for 3 weeks. The patient had a past medical history of Hypertension, alcoholism, and REM sleep disorder. He was being treated for erectile dysfunction for the last 10 years and had a family history of Parkinson's disease in his mother and sister. The patient was compliant with Lisinopril 40 mg, Amlodipine, and Rosuvastatin, Tamsulosin 0.4 mg. His blood pressure(BP) on presentation was ranging between 109/74-194/76 mm of Hg. Systolic BP dropped by 30mmHg after tilting the angle of the bed to 45 degrees for 1 minute with no change in HR and the patient became symptomatic in this position. Orthostatic vitals showed a dramatic drop in Systolic BP of >80mmHg with no change in heart rate. MRA and MRI showed chronic microvascular changes. The Echocardiogram, Cortisol, and TSH levels were all normal. All anti-hypertensives were discontinued and supportive treatment was started with Midodrine, Droxidopa, and Pyridostigmine, thigh-high TED hose and abdominal binders at bedtime, and Nitroglycerin patch at night for hypertension. The patient was started on fludrocortisone as he continued to drop his BP by 80 mmHg on standing. The use of TED stockings and bed tilting improved the issue of uncontrolled supine hypertension at night. Conclusion- Treatment of autonomic dysfunction continues to be challenging. There are no definitive guidelines and management is largely individualized. Both pharmacological and non-pharmacological measures are used.

<p>Reduced kidney function around the time of surgery is an important risk factor for postoperative mortality. Despite this there is limited information on how reduced kidney function prior to surgery alters prognosis, what causes sudden decrements in kidney function after surgery (known as acute kidney injury), or how they might be avoided. The studies in this thesis inform these knowledge gaps. Chapter 2 describes the results of a post hoc analysis of the interaction between preoperative estimated glomerular filtration rate, a marker of kidney function, and postoperative cardiac troponin T, a marker of heart damage, for predicting 30-day mortality in a prospective cohort study of patients undergoing noncardiac surgery. Chapter 3 uses administrative and clinical data from a single centre to inform the risk of acute kidney injury after noncardiac surgery by concentrations of preoperative hemoglobin and change in postoperative hemoglobin. Chapter 4 uses the same data to determine a definition of intraoperative hypotension that is prognostic of acute kidney injury, myocardial injury and death. Chapter 5 describes a randomized controlled trial that compares a novel therapeutic procedure called remote ischemic preconditioning to a sham procedure in patients undergoing cardiac surgery.</p> / Doctor of Philosophy (PhD)

Three clinical investigations together with a combined editorial and review of the cardiovascular physiology of spinal anaesthesia in normal and preeclamptic pregnancy form the basis of a thesis to be submitted for the degree of Doctor of Medicine at the University of St Andrews. First, the longstanding consensus that spinal anaesthesia could cause severe hypotension in severe preeclampsia was examined using three approaches. The doses of ephedrine required to maintain systolic blood pressure above predetermined limits were first compared in spinal versus epidural anaesthesia. The doses of ephedrine required were then similarly studied during spinal anaesthesia in preeclamptic versus normal control subjects. The principal outcome of these studies, that preeclamptic patients were resistant to hypotension after a spinal anaesthetic, was then further investigated by studying pulse transit time (PTT) changes in normal versus preeclamptic pregnancy. PTT was explored both as beat-to-beat monitor of cardiovascular function and also as an indicator of changes in arterial stiffness. The cardiovascular physiology of obstetric spinal anaesthesia was then reviewed in the light of the three clinical investigations, developments in reproductive vascular biology and the regulation of venous capacitance. It is argued that the theory of a role for vena caval compression as the single cause of spinal anaesthetic induced hypotension in obstetrics should be revised.

L’encéphalopathie hépatique (EH) est une complication neuropsychiatrique de la maladie de foie telle que la cirrhose, caractérisée par des dysfonctions cognitives et motrices. Le seul traitement curatif est la transplantation hépatique (TH). Historiquement, l’EH est considérée comme un désordre métabolique réversible et il est attendu qu’il soit résolu suivant la TH. Cependant, il a été démontré que des complications neurologiques persistent chez 47% des patients transplantés. La TH est une opération chirurgicale complexe accompagnée de stress péri-opératoire telle que la perte sanguine et l’hypotension. L’hypothèse de ce projet d’étude est que l’EH minimale (EHm) rend le cerveau plus susceptible à une perte neuronale suite à une insulte hypotensive. Nous avons donc caractérisé un modèle d’hypotension chez des rats cirrhotiques avec ligation de la voie biliaire (BDL) dans lequel une hypovolémie de l’artère fémorale a été faite. Avec ce modèle, nous avons étudié l’impact de différentes pressions sanguines de 120 minutes sur le compte neuronal. Nos résultats démontrent que les BDL hypotendus à une pression artérielle moyenne de 60 mmHg et 30 mmHg ont une diminution du compte neuronal et que les neurones mourraient par apoptose (observée par la présence de caspase-3 clivée). Nous avons également déterminé que le flot sanguin cérébral était altéré chez les rats cirrhotiques BDL. Le second objectif était d’évaluer si le traitement de l’EHm par l’ornithine phénylacétate (OP) permettait d’éviter la perte neuronale chez les BDL hypotendus. Nos résultats ont démontrés que l’OP permettait de partiellement rétablir les fonctions cognitives chez les rats BDL. De plus, les rats BDL traités avec l’OP peuvent éviter la mort neuronale. Cependant, le processus apoptotique est toujours enclenché. Ce résultat suggère la possibilité de mort cellulaire retardée par l’OP. Ces résultats suggèrent que les patients cirrhotiques avec EHm sont plus susceptibles à une mort neuronale induite par hypotension. La combinaison de l’EHm et l’hypotension permet d’expliquer les complications neurologiques rencontrées chez certains patients. Le diagnostic et le traitement de ce syndrome doit donc être fait chez les patients cirrhotiques pour éviter ces complications post-TH. / Hepatic encephalopathy (HE) is a major neuropsychiatric complication caused by chronic liver disease such as cirrhosis and is characterized by cognitive and motor dysfunction. The only curative treatment to date remains liver transplantation (LT). Historically, HE has always been considered to be a reversible metabolic disorder and has therefore been expected to completely resolve following LT. However, persisting neurological complications remain a common problem affecting as many as 47% of LT recipients. LT is a major surgical procedure accompanied by intraoperative stress and confounding factors, including blood loss and hypotension. We hypothesize, in the setting of minimal HE (MHE), the compromised brain becomes susceptible to hypotensive insults, resulting in cell injury and death. To investigate this hypothesis, six-week bile-duct ligated (BDL) rats with MHE and respective controls (SHAM) were used. Blood is withdrawn from the femoral artery (inducing hypovolemia) until a mean arterial pressure of 30, 60 and 90 mmHg (hypotension) and maintained for 120 minutes. Our results demonstrated that BDL with following hypotension of 30 and 60 mmHg have a lower neuronal cell count compared to SHAM-operated animals. Furthermore, we provide evidence neuronal cell death is occurring due to apoptosis (observed by presence of cleaved caspase-3). In addition, cerebral blood flow is reduced in BDL rats compared to SHAM-operated controls. Second objective was to assess the therapeutic potential of the ammonia-lowering agent ornithine phenylacetate (OP) in preventing hypotension-induced neuronal loss in BDL rats. OP-treated BDL rats, in addition to lowering blood ammonia, also ameliorated cognitive function. However, cleaved caspase-3 levels were still elevated in the brains of OP-treated BDL rats therefore suggesting OP delays the onset of neuronal death in BDL rats. Overall, these findings strongly suggest that cirrhotic patients with MHE are more susceptible to hypotension-induced neuronal cell loss. Moreover, these results suggest a patient with HE (even MHE), with a “frail brain”, will fare worse during LT transplantation and consequently result in poor neurological outcome. Combination of MHE and hypotension may account for the persisting neurological complications observed in a number of cirrhotic patients following LT. Therefore, MHE, i) should not be ignored and therefore diagnosed and ii) merits to be treated in order to reduce the risk of neurological complications occurring post-LT

La dépression (caractérisée ou subsyndromique) est fréquente tout au long de la vie et les démences sont des pathologies fréquentes du sujet âgé. Une association longitudinale entre la dépression ou les symptômes dépressifs et la démence a été rapportée. Cependant, le sens de cette association demeure incertain et ses mécanismes pathogéniques selon l’âge de l’apparition des manifestations dépressives sont largement méconnus. Les facteurs de risque vasculaires sont associés à la démence et une comorbidité vasculaire est également retrouvée chez le sujet âgé dépressif. L’hypothèse qu’un ou des facteurs de risque cardiovasculaires constitue(nt) l’ultime dénominateur commun des troubles de l’humeur et de démences devrait être vérifié. L’objectif de cette thèse était d’étudier les liens entre la pression artérielle, la dépression et la démence. Dans un échantillon de 9294 sujets âgés de 65 ans et plus (Etude 3C), non institutionnalisés, suivis pendant 4 ans, nous avons retrouvé une association entre les symptômes dépressifs sévères à l’inclusion et le risque de démence (en particulier vasculaire) incidente. A l’opposé, les antécédents dépressifs n’augmentaient pas le risque de démence. Nos analyses transversales indiquaient une pression artérielle plus basse chez les sujets dépressifs comparés aux sujets non dépressifs. Pour terminer, l’association entre les symptômes dépressifs sévères et la démence n’était pas médiée par l’hypertension artérielle. Nos résultats indiquent que les symptômes dépressifs semblent constituer une expression non cognitive de la phase prodromale de la démence plutôt que d’en être un facteur de risque. L’explication d’une pression artérielle plus basse chez les sujets dépressifs comparés aux sujets non dépressifs n’est pas univoque. Une pression artérielle basse pourrait conduire à une hypoperfusion cérébrale, corrélée aux lésions de la substance blanche dans les régions les plus sensibles aux modifications du flux sanguin cérébral et dont l’altération est associée aux manifestations dépressives et cognitives. Ce travail offre de nouvelles perspectives de définition des groupes de population à haut risque de démence, et des perspectives de recherche sur les mécanismes biologiques liant la pression artérielle et la dépression. D’un point de vu méthodologique, il met l’accent sur la nécessité des méthodes d’évaluation fiables et précises des cas pathologiques (dépressifs et déments), lesquels influencent réciproquement l’évaluation de chacun. / Depression is highly common throughout the life course and dementia is common in late life. Depression has been linked with dementia, yet the direction and pathological mechanisms of this association (whether depression is a prodromal feature or consequence of, or a risk factor for dementia) remains unclear. Vascular risk factors are associated to the risk of incident cognitive impairment and dementia and comorbid vascular disease is a feature of depression in latelife. Therefore, the hypothesis that vascular risk factors are the ultim denominator of psychological perturbations and dementia is to be verified. The aim of this work was to study the links between blood pressure, depression and dementia. In a cohort of 9294 community-dwelling elderly individuals aged 65 years and over, participating to the longitudinal population-based 3 City Study, followed up for 4 years, we found an association between baseline depressive symptoms’ severity and the incident dementia risk (particularly of vascular type). Conversely, we found no association between history of depression and incident dementia. Moreover, our cross sectional analyses exhibited an inverse association between systolic and diastolic blood pressure values and depression. Overall, however, the association between depressive symptoms and dementia was not mediated by hypertension. These results indicate that depression is rather a prodromal symptom of vascular dementia than a risk factor for it. The explanation for the inverse association found between blood pressure values and depression is not straightforward. Low blood pressure may lead to cerebral hypoperfusion found to be associated with white matter lesions in cerebral regions vulnerable to alterations of cerebral blood flow, and associated with cognitive impairment and depression. This work offers the opportunity for the definition of group of populations at high risk to develop dementia, vascular one in particular. It also gives the perspective of research on the biological mechanisms linking blood pressure and depression. From a methodological point of view, it emphasizes the need for instruments assessing precisely and thoroughly these two conditions which influence the assessment of each other.