Dissertations / Theses on the topic 'Renal blood flow'

Autosomal dominant polycystic disease (ADPKD) is the most common hereditary renal disease and is characterized by renal cyst growth and enlargement. Hypertension occurs early when renal function is normal and is characterized by decreased renal blood flow. Accordingly, the measurement of blood flow in the renal arteries can be a valuable tool in evaluating disease progression. In studies performed in conjunction with this work, blood flow was measured through the renal arteries using magnetic resonance imaging (MRI). In order to validate these in vivo measurements, a vascular phantom was created using polyvinyl alcohol (PVA) and also scanned using MRI under controlled steady flow conditions. Ranges of vessel diameters and flow velocities were used to simulate actual flow in a normal and diseased population of adults and children. With the vessel diameters studied in this experiment, minimization of field of view and an increase in spatial resolution is important in obtaining accurate data. However, a significant difference does not exist between the results when using the 160 or 200 mm FOV. An increase in the number of phase encodings provides improved results, although an increase in image acquisition time is observed. Velocity-encoding in all three orthogonal directions does not improve image data. This method of using MRI to measure flow through a vessel is shown to be both accurate and reproducible, and the protocol providing the most correct results is prescribed. Breath-hold phase-velocity encoded MRI proves to be an accurate and reproducible technique in capturing flow and has the potential to be used for the purpose of observing hemodynamic changes in the renal arteries with the progression of ADPKD.

Acute renal failure (ARF) is a common condition on the intensive care unit (ICU) and may affect up to 40% of patients (de Mendonca, A. et al., 2000), (Korkeila, M. et al., 2000). Pathophysiological mechanisms remain unclear. Patients who die from sepsis have kidneys that look histologically normal (Hotchkiss, R.S. et al., 1999), while the renal prognosis in survivors is good with < 2% requiring long-term renal replacement therapy (Noble, J.S. et al., 2001). This has led some authors to suggest that acute renal failure is a physiological process designed to shut down vital processes and protect the kidney from irreversible damage during a severe insult (Singer, M. et al., 2004). As ninety percent of oxygen consumption is utilised by the mitochondrion (Babcock, G.T. and Wikstrom, M., 1992), metabolic control may be regulated by mitochondrial activity (Beltran, B. et al., 2000). This may be an important mechanism underlying renal failure but is difficult to assess in the intact animal.

Dissertation (MD)--Stellenbosch University, 2000.
ENGLISH ABSTRACT: Acute renal failure still is, with the exception of cardiac deaths, the most important pathological process associated with perioperative mortality in patients operated for abdominal aortic aneurysms. The intraoperative change in renal blood flow (RBF) and glomerular function have been investigated in human and animal models, particularly over the past 15 years. Despite large variation in study populations, measurement techniques and study designs in general, a significant body of evidence has developed which suggests infrarenal aortic clamp-induced renal ischemia to be the cause of postoperative acute renal failure when this complication does occur. It is rather surprizing then that, despite some recent studies which have reported on various pharmacological interventions to prevent intraoperative renal ischemia (with variable success), very little has apparently been done to unravel the pathogenesis and exact pathophysiology of this potentially lethal complication. Although a number of investigators suggest the possibility of hormonal involvement (particularly reninangiotensin, antidiuretic hormone (ADH) and catecholamines) in the process, the exact role of these mediators have not been explored (or reported) in a structured fashion. In an initial human study, renal hemodynamics and function were measured from the preoperative period, during the intraoperative phase and at least until 4 hours after aortic unclamping. To investigate the possibility of a temporal relationship between renal changes and fluctuations in hormonal concentrations, plasma concentrations of relevant hormones were determined at every sampling period where renal parameters were measured. The decrease in RBF and glomerular filtration rate (GFR) which we demonstrated to coincide with infrarenal aortic cross clamping, is consistent with results previously published. We demonstrated persistence of the impairment of these parameters as long as 4 hours into the postoperative phase; which has previously only been reported for the period until immediately after aortic unclamping with the abdomen still open. The persistence of a depressed GFR until the time of discharge of patients is cause for concern, particularly in patients with compromised renal function prior to surgery. Of the measured hormones with a potential influence on RBF and nephron function, renin was the only mediator where changes in plasma concentrations coincided with the depression of RBF and GFR after aortic cross clamping. The design of our study did not allow us to conclude whether the concomitant increase in angiotensin II was primarily responsible for the change in renal hemodynamics, or whether the raised renin (and angiotensin) levels were stimulated by the decrease in RBF induced by another mechanism. In another patient group, we demonstrated that the combination of mannitol and dopamine provided no protection against the deleterious effects of aortic cross clamping. In fact, the high urine volumes produced under the influence of these agents (which did not correlate with RBF at the corresponding periods), is likely to prompt a false sense of security. Given the lack of any objective benefit afforded by these agents, their use in these clinical circumstances should be discouraged. The animal studies were aimed at elucidation of the exact role of angiotensin in the pathogenesis and pathophysiology of the renal changes associated with infrarenal aortic clamping, as well as the interaction of angiotensin with other modulators for which an interactive relationship had been described previously under other experimental and/or clinical circumstances. The first study showed that, although renin (and thus angiotensin) concentrations were high after aortic unclamping, the hormone had no pathogenic or pathophysiological role of significance in the observed renal changes during this period (since blocking angiotensin II activation by the prevention of renin release, or by inhibiting the conversion enzyme, did not prevent a substantial decrease in RBF or GFR during that period). Preventing angiotensin II activation did, however, prevent renal changes during aortic clamping. This beneficial effect did not establish a primary role for angiotensin during that period, since the favourable influence could also (at least partially) be explained by prevention of the permissive influence of angiotensin on other vasoconstrictors and/or other vasodilatory influences of ACE inhibition and [1- blockade which are unrelated to angiotensin. This study did indicate that (at least partially) different mechanisms are responsible for the renal changes seen during aortic clamping, and after aortic unclamping. The second study explored the role of calcium in the renal pathophysiological changes during aortic clamping and after unclamping. The protective influence effected by the administration of a Ca2 + -blocker suggest the dependence of the renal vasoconstrictive and glomerular pathophysiological process( es) on the cellular influx of Ca2 + through voltage-gated channels. It unfortunately provides no definitive insight into the primary instigators of these processes. However, it does offer a clinically useful method of preventing these changes and protecting the kidney against ischemic injury during abdominal aortic surgery. The third component of the animal studies demonstrates the importance of the protective effect of renal prostaglandins during the specific experimental (and probably also the clinical) circumstances. Again, it does not provide definitive information on the mediators responsible for the renal changes, since the deleterious effects of numerous endogenous substances have previously been shown to be counterbalanced by intrarenal synthesis of prostaglandins under various experimental and clinical circumstances. The extent of the pathophysiological and ultrastructural changes which occurred under the influence of a NSAID does, however, suggest that these drugs should not be used under these clinical circumstances. The last component of the study provides evidence that angiotensin only plays a secondary/supplementary role in the renal pathophysiological process even during aortic clamping. This may explain the contradictory evidence regarding the potential beneficial effect of ACE inhibition (on renal hemodynamics and glomerular function) during abdominal aortic surgery (Licker et al. 1996, Colson et al. 1992a). Based on our studies, ACE inhibition can not be supported for this purpose.
AFRIKAANSE OPSOMMING: Akute nierversaking is met die uitsondering van kardiale sterftes, steeds die belangrikste patologiese proses wat geassosieer is met perioperatiewe mortaliteit in pasiënte wat opereer word vir abdominale aorta aneurismes. Die intraoperatiewe veranderinge in renale bloedvloei (NBV) en glomerulêre funksie is die afgelope 15 jaar ondersoek en gerapporteer in pasiënte- sowel as diere-modelle. Ten spyte van groot variasies in studie-populasies, meettegnieke en ontwerp van studies in die algemeen, dui 'n wesenlike hoeveelheid getuienis daarop dat infrarenale klemming van die aorta renale isgemie induseer, wat die oorsaak is van postoperatiewe akute nierversaking wanneer hierdie komplikasie voorkom. Dit is verbasend dat, ten spyte van sommige onlangse studies wat rapporteer oor 'n verskeidenheid farmakologiese ingrepe om intraoperatiewe renale isgemie te voorkom (met wisselende sukses), baie min oënskynlik gedoen is om die patogenese en die presiese patofisiologie van hierdie potensieel dodelike komplikasie te ontrafel. Hoewel verskeie outeurs die moontlikheid van hormonale betrokkenheid (veral renienangiotensien, antidiuretiese hormoon en katekolamiene) in hierdie proses suggereer, is die presiese rol van hierdie mediators nog nie op 'n gestruktureerde wyse ondersoek (of rapporteer) nie. In ons aanvanklike pasiënte-studie is renale hemodinamika en -funksie gemeet vanaf die preoperatiewe periode, gedurende die intra-operatiewe fase en tot minstens vier uur na ontklemming van die aorta. Serumkonsentrasies van relevante hormone is bepaal tydens elke metingsperiode waar renale parameters gemeet is, ten einde die moontlikheid van 'n temporale verwantskap tussen renale veranderinge en variasies in hormoonkonsentrasies te ondersoek. Die vermindering in NBV en glomerulêre filtrasiespoed (GFS) wat ons aangetoon het om saam te val met infrarenale aortaklemming, stem ooreen met resultate wat tevore deur ander navorsers publiseer is. Ons het aangetoon dat die inkorting van hierdie parameters voortduur tot minstens vier uur na aorta-ontklemming. Hierdie veranderinge is tevore slegs rapporteer vir periodes tot kort na aorta-ontklemming voor sluiting van die buikwond. Die feit dat die GFS steeds verlaag is met ontslag van hierdie pasiënte, skep rede tot kommer, veral in pasiënte wat alreeds ingekorte nierfunksie het voor die chirurgiese prosedure. Van die gemete hormone wat moontlik 'n invloed sou kon uitoefen op NBV eh nefronfunksie, was renien die enigste waarvan verandering in plasmakonsentrasies saamgeval het met die onderdrukking van NBV en GFS na aortaklemming. Die ontwerp van ons studie het ons nie toegelaat om 'n besliste uitspraak te maak of die geassosieerde verhoging in angiotensien II primêr verantwoordelik was vir die verandering in renale hemodinamika, of dat die verhoogde renien (en angiotensien) bloedvlakke moontlik sekondêr stimuleer is deur die verandering in NBV wat deur 'n ander meganisme induseer is. In 'n ander pasiëntegroep het ons aangetoon dat die kombinasie van mannitol en dopamien geen beskerming verleen het teen die nadelige effekte van aorta-klemming nie. Die groot volumes uriene wat uitgeskei is onder die invloed van hierdie middels (wat nie korreleer het met NBV tydens ooreenstemmende periodes nie), het inderwaarheid 'n ontoepaslike gerustheid uitgelok. Weens die ooglopende gebrek aan objektiewe voordeel wat verleen word deur hierdie middels, behoort hulle gebruik tydens hierdie kliniese omstandighede ontmoedig te word. Die doel van die diere studies was die identifisering van die presiese rol van angiotensien in die patogenese en patofisiologie van die renale veranderinge geassosieer met infrarenale aortaklemming, sowel as die interaksie van angiotensien met ander modulators waarvoor 'n interaktiewe verwantskap voorheen beskryf is onder eksperimentele en/of kliniese omstandighede. Die eerste studie het getoon dat alhoewel renien (en dus angiotensien) konsentrasies hoog was na aorta-ontklemming, die hormone geen betekenisvolle patogenetiese of patofisiologiese rol in die waargenome renale veranderinge gedurende hierdie periode het nie (aangesien blokkade van angiotensien aktivering deur voorkoming van renien vrystelling, of deur inhibisie van angiotensien omsettingsensiem (AOE), nie 'n daling in NBV of GFS kon voorkom nie). Voorkoming van angiotensien II aktivering het egter wel renale verandering voorkom gedurende aortaklemming. Dié voordelige effek het nie 'n primêre rol vir angiotensien gedurende die periode bevestig nie, aangesien die gunstige invloed ook (ten minste gedeeltelik) verduidelik kon word deur die voorkoming van die fassiliterende invloed van angiotensien op ander vasokonstriktore en/of ander vasodilator-invloede van die onderdrukking van AOE en ïs-blokkers (wat geen verband het met angiotensien of die blokkade daarvan nie). Die studie het aangetoon dat (ten minste gedeeltelik) verskillende meganismes verantwoordelik is vir renale veranderinge wat gesien is gedurende aortaklemming en na -ontklemming. Die tweede studie het die rol van kalsium in die renale patofisiologiese veranderinge gedurende aortaklemming en na ontklemming ondersoek. Die beskermende invloed wat deur die toediening van Ca2 + -blokkers bewerkstellig is, het bevestig dat die renale vasokonstriktoriese en glomerulêre patofisiologiese prosesse afhanklik is van sellulêre influks van kalsium deur spannings-afhanklike kannale. Dit het ongelukkig geen definitiewe insig verleen ten opsigte van die primêre inisieerders van die proses nie. Dit verskaf nogtans 'n bruikbare kliniese metode om daardie veranderinge te voorkom en die niere teen isgemiese besering gedurende abdominale aorta-chirurgie te beskerm. Die derde komponent van die diere-studies demonstreer die belangrikheid van die beskermende effek van renale prostaglandiene tydens die spesifieke eksperimentele (en waarskynlik ook die kliniese) omstandighede. Weereens gee dit nie definitiewe inligting oor die bemiddelaars wat verantwoordelik is vir die renale veranderinge nie, aangesien die skadelike effekte van verskeie endogene stowwe voorheen aangetoon is om beperk of voorkom te word deur die intrarenale vrystelling van prostaglandiene. Die omvang van die patofisiologiese en ultrastrukturele veranderinge wat ontstaan het onder die invloed van nie-steroïed anti-inflammatoriese middels (wat gebruik is om prostaglandien sintese te inhibeer), dui aan dat hierdie middels vermy moet word onder soortelyke kliniese omstandighede. Die laaste komponent van die studie verskaf 'n sterk aanduiding dat angiotensien slegs 'n sekondêre/aanvullende rol speel in die renale patofisiologiese proses, selfs gedurende aortaklemming. Dit mag die weersprekende getuienis oor die potensiële voordeel van AOE onderdrukking (op renale hemodinamika en glomerulêre funksie) gedurende abdominale aortachirurgie (Licker et al. 1996, Colson et al. 1992a) verklaar. Gebaseer op ons studies, kan AOE onderdrukking nie ondersteun word vir hierdie doel nie.

The etiology of renal dysfunction in sepsis is currently attributed to altered perfusion, microcirculatory abnormalities and cellular alterations. To clarify these mechanisms, we characterized the changes in renal perfusion and cortex metabolism in a large animal model of sepsis. In this model, sepsis was associated with metabolic alterations that may reflect early induction of cortical glycolysis. Septic shock was associated with reduced renal perfusion and decreased cortical and medullary blood flow, followed by signs of anaerobic metabolism in the cortex when flow reductions became critical. Attempts to correct renal hypoperfusion and alleviate the associated perfusion/metabolism mismatch with fenoldopam or renal denervation were unsuccessful. In the final study we focussed on the role of renal autoregulation in experimental sepsis and septic shock. Evidence suggests that higher blood pressure targets are needed in patients with impaired renal autoregulation and septic shock, but the effects of vasopressors should also be considered. We therefore investigated the effects of arginine vasopressin and norepinephrine on renal autoregulation in ovine septic shock. In experimental septic shock, arginine vasopressin was associated with a lower autoregulatory threshold than norepinephrine. As vasopressors may have different effects on renal autoregulation, individualized therapy of blood pressure management in patients with septic shock should take into account drug-specific effects.
Doctorat en Sciences médicales (Médecine)
info:eu-repo/semantics/nonPublished

Orientador: Áureo Evangelista Santana
Resumo: A anemia é considerada um dos fatores para avaliar progressão da doença renal e diminuição da qualidade de vida do paciente. Conforme a doença renal progride, ocorre aumento gradativo na produção de toxinas urêmicas que reduz a meia vida dos eritrócitos circulantes por interferir na estabilidade da membrana eritrocitária. Para tanto, utiliza-se a contagem de reticulócitos para classificar a anemia como regenerativa ou não regenerativa. Objetivou-se neste estudo avaliar a resistência da membrana das hemácias, utilizando-se do teste de Fragilidade Osmótica Eritrocitária (FOE) em cães com doença renal crônica (DRC) e avaliação de reticulócitos. Foram avaliados 43 cães provenientes da rotina do Serviço de Nefrologia e Urologia do Hospital Veterinário Governador Laudo Natel da Faculdade de Ciências Agrárias e Veterinárias - UNESP - campus Jaboticabal. As referidas unidades experimentais foram distribuídas em três grupos, quais sejam, G0 (n=13), composto por cães hígidos e G1, DRC estádios 1 e 2 (n=14) e G2, DRC estádios 3 e 4 (n=16), classificados de acordo com o recomendado pela International Renal Interest Society. A fim de definir os critérios de inclusão dos cães foram feitos, além do exame físico, a avaliação de pressão arterial, hemograma, contagem de reticulócitos, exames bioquímicos, urinálise e relação proteína/creatinina urinária (UP/C). Para execução do teste de FOE as hemácias foram diluídas em concentrações decrescentes de cloreto de sódio e analisadas por citometria ... (Resumo completo, clicar acesso eletrônico abaixo)
Abstract: Anemia is considered one of the factors to assess the kidney disease progress and the decrease in patient's quality of life. As kidney disease progresses, there is a gradual increase in urinary toxin production that shortens the circulating erythrocyte half-life by interfering with erythrocyte membrane stability. To do this, use a reticulocyte count to classify anemia as regenerative or non-regenerative. The objectives of this study were to evaluate the resistance of the red blood cells, using the Erythrocyte Osmotic Fragility test in dogs with chronic kidney disease (CKD) and to evaluate reticulocytes. Forty-three dogs were charged, followed by the routine of the Nephrology and Urology Service of the Governor Laudo Natel Veterinary Hospital of the Faculty of Agricultural and Veterinary Sciences - UNESP - Campus Jaboticabal. The experimental units were divided into three groups, namely, G0 (n = 13), consisting of healthy dogs and G1, CKD stages 1 and 2 (n = 14) and G2, CKD stages 3 and 4 (n = 16), classification proposed by the International Renal Interest Society. In order to define the inclusion criteria of dogs made, in addition to physical examination, an assessment of blood pressure, blood count, reticulocyte count, biochemical tests, urinalysis, and urinary protein/creatinine ratio. To perform the erythrocyte osmotic fragility test, red blood cells were diluted in decreasing sodium chloride filters (0.9 to 0.0%) and analyzed by flow cytometry. As creatinine serum concen... (Complete abstract click electronic access below)
Mestre

Está bem documentada a importância da disfunção autonômica na evolução das complicações do Diabetes. Adicionalmente, novas e consistentes evidências indicam que o controle reflexo da circulação comandado pelos baroreceptores poderia ser um marcador prognóstico precoce no Diabete melito, clínico e experimental. No presente projeto, testamos a hipótese de que a disfunção barorreflexa interfere no desenvolvimento da nefropatia e cardiomiopatia diabética por alterar a modulação autonômica comandada pelos barorreceptores arteriais sobre vasos e coração. Foram utilizados ratos Wistar machos (230 a 260g) divididos em 4 grupos experimentais: controle (GC, n=9), diabético (GD, n=11), desnervado (GCD, n=9) e desnervado diabético (GDD, n=8). Após 7 dias de desnervação sinoaórtica, foi realizada a indução do diabetes (DM) por estreptozotocina (STZ). Foram realizadas avaliações metabólicas, teste de tolerância a glicose e avaliações ecocardiográficas durante a terceira semana do protocolo. A partir dos 28 dias de protocolo foram realizados registros diretos da pressão arterial (PA) e avaliações da sensibilidade barorreflexas, da modulação autonômica cardiovascular (variabilidade da freqüência cardíaca e da PA sistólica), análise dos fluxos sanguíneos regionais e avaliações renais ex vivo. Os grupos diabéticos (GD e GDD) apresentaram aumento da glicemia e redução do peso corporal, da PA e da freqüência cardíaca quando comparados com os grupos não diabéticos (GC e GCD). Os grupos diabéticos apresentaram uma maior área de resposta sob a curva de resposta glicêmica quando comparados aos grupos controle, indicando assim uma intolerância maior a glicose. Nos parâmetros morfométricos, o septo interventricular (SIVDIA) mostrou-se menor nos grupos diabéticos quando comparados ao GC. A parede posterior do ventrículo esquerdo (PPDIA) mostrou-se diminuída somente no grupo diabético. Com relação ao tamanho da cavidade do ventrículo esquerdo na diástole (VEDIA), observou-se uma tendência a aumento em todos os grupos quando comparados ao controle. A massa do ventrículo esquerdo (MVE) foi menor no grupo diabético em relação ao controle e maior nos grupos submetidos à DSA quando comparados ao GC. A função sistólica foi avaliada pela fração de ejeção (FE), na qual não foi observada diferença entre os grupos estudados. A função diastólica foi avaliada pelo tempo de relaxamento isovolumétrico (TRIV) que foi maior no grupo diabético quando comparado ao controle. Já o grupo desnervado apresentou valores próximos ao do GC. Entretanto, o grupo desnervado diabético apresentou valores menores de TRIV quando comparado aos animais apenas diabéticos. Disfunção autonômica, avaliada pela sensibilidade barorreflexa, pela variabilidade da FC (VFC) e da PA sistólica (VPAS), foram observadas nos grupos GD, GCD e GDD em relação ao grupo C. Os fluxos sanguíneos analisados nesse protocolo (coronariano, pulmonar, renal e muscular) apresentaram-se reduzidos em todos os grupos experimentais quando comparados ao GC. O grupo submetido à SAD mostrou uma redução mais acentuada em todos os fluxos sanguíneos estudados. A resistência vascular periférica total encontra-se aumentada em todos os grupos analisados com um aumento maior nos grupos diabéticos. O débito cardíaco mostrou-se reduzido em todos os grupos estudados, em especial no grupo desnervado diabético, quando comparados com o GC. Com relação ao índice cardíaco, também observamos uma redução em todos os grupos, com uma redução maior nos grupos diabéticos sendo que a desnervação não foi capaz de atenuar essa redução no grupo desnervado diabético. A avaliação renal mostrou um aumento da pressão de perfusão do GD, acompanhado por um aumento significativo na resistência vascular renal, no fluxo urinário, no ritmo de filtração glomerular. Dessa forma, os resultados obtidos no presente trabalho fornecem evidencias de que o papel homeostático do baroreflexo é essencial no curso das alterações cardíacas e renais tanto em animais normoglicêmicos como nos hiperglicêmicos, por sua ação não só no controle das variações momento a momento (labilidade) como também interferindo em alterações sustentadas da PA, como observado nesse trabalho. Esses resultados poderão dar suporte a estudos populacionais que associam maior sensibilidade do baroreflexo com melhor prognóstico e sobrevida após evento cardiovascular em indivíduos diabéticos
It is well documented the importance of autonomic dysfunction in microvascular complications of diabetes. Additionally, new and consistent evidence indicates that the reflex control of movement is controlled by the baroreceptors could be an early prognostic marker in diabetes mellitus, clinical and experimental. In this project, we tested the hypothesis that baroreflex dysfunction interferes with the development of nephropathy and diabetic cardiomyopathy by altering the autonomic modulation controlled by the arterial baroreceptors on heart and blood vessels. We used male Wistar rats (230 to 260g) were divided into four groups: control group (n = 9), diabetic (GD, n = 11), denervated (GCD, n = 9) and diabetic denervated (GDD, n = 8). After 7 days of sinoaortic denervation was performed we induced diabetes (DM) by streptozotocin (STZ). We evaluated metabolic, glucose tolerance test and echocardiographic evaluations during the third week of the protocol. After 28 days of protocol records were taken direct blood pressure (BP) and baroreflex sensitivity assessments of cardiovascular autonomic (heart rate variability and systolic BP), regional blood flow analysis and evaluations kidney ex vivo. Diabetic groups (GD and GDD) had higher blood glucose and reduced body weight, blood pressure and heart rate when compared with non-diabetic groups (GC and GCD). Diabetic groups showed a larger response area under the glycemic response curve when compared to control groups, thus indicating an increased glucose intolerance. The morphometric parameters, interventricular septum (IVSD) was lower in both diabetic groups compared to CG. The back wall of the left ventricle (PPDIA) was reduced only in diabetic mice. Regarding the size of the cavity of the left ventricle during diastole (Vedia), there was a tendency to increase in all groups compared to control. The left ventricular mass (LVM) was lower in the diabetic group compared to control, and higher in the groups submitted to DSA when compared to CG. Systolic function was evaluated by ejection fraction (EF), in which there was no difference between groups. Diastolic function was evaluated by isovolumic relaxation time (IVRT) was greater in the diabetic group compared to control. The denervated group showed similar to the CG. However, the denervated diabetic group showed lower values of IVRT as compared to diabetic animals only. Autonomic dysfunction, as assessed by baroreflex sensitivity by HR variability (HRV) and systolic (VPAS) were observed in groups GD, GCD and GDD than in group C. The blood flows analyzed in this protocol (coronary, pulmonary, kidney and muscle) were reduced in all experimental groups compared to CG. The group submitted to SAD showed a marked reduction in all blood flows studied. The total peripheral vascular resistance is increased in all groups with a greater increase in the diabetic group. Cardiac output was reduced in all groups, especially in denervated diabetic group compared with the GC. With respect to cardiac index, we also observed a reduction in all groups, with a greater reduction in the diabetic group and that denervation was not able to mitigate this reduction in denervated diabetic group. The evaluation showed an increase in renal perfusion pressure of the GD, accompanied by a significant increase in renal vascular resistance, urinary flow, the glomerular filtration rate. Thus, the results obtained in this study provide evidence that the homeostatic role of the baroreflex is essential in the course of changes in both heart and kidney as in hyperglycemic animals normoglycemic by acting not only in control of changes moment to moment (lability) as well as interfering with sustained changes in BP, as observed in this study. These results could support population studies linking higher sensitivity of the baroreflex with a better prognosis and survival after a cardiovascular event in diabetic subjects

The hypothalamic paraventricular nucleus (PVN) is known to be a major integrative region within the forebrain. It is composed of functionally different subgroups of neurons, including the parvocellular neurons that project to important autonomic targets in the brainstem e.g. the rostral ventrolateral medulla (RVLM) and the intermediolateral cell column (IML) of the spinal cord, where the sympathetic preganglionic motor-neurons are located. These regions are critical in cardiovascular regulation; hence, these projections are likely to mediate the effects of the PVN on sympathetic nerve activity and hence may contribute to the cardiovascular changes induced by physiological stimuli such as elevations in body temperature. The neurotransmitter such as nitric oxide (NO) is important in cardiovascular regulation and it is now emerging as a major focus of investigation in thermoregulation. One of the most striking accumulations of NO containing-neurons is in the PVN where it appears to be playing an important role in cardiovascular regulation and body fluid homeostasis. The results of the work show; 1. That spinally-projecting and nitrergic neurons in the PVN may contribute to the central pathways activated by exposure to a hot environment. 2. Suggests that nitrergic neurons and spinally- projecting neurons in the brainstem may make a small contribution to the central pathways mediating the reflex responses initiated by hyperthermia. 3. The present study also illustrates that these PVN neurons projecting to the RVLM may make a smaller contribution than the spinal-projecting neurons in the PVN to the cardiovascular responses initiated by heat. 4. The results of my studies showed that the microinjection of muscimol to inhibit the neuronal activity in the PVN abolished the reflex decrease in renal blood flow following an elevation of core body temperature. In addition, this effect was specific to the PVN, since microinjections of muscimol into areas outside the PVN were not effective. These findings demonstrate that the PVN is critical for this reflex cardiovascular response initiated by hyperthermia. In conclusion, PVN is critical for the reflex decrease in renal blood flow during elevations in core body temperature. We hypothesise that projections from the PVN to the spinal cord and the RVLM contribute to the reflex cardiovascular responses. Additionally, nitrergic neurons in the PVN may contribute but the physiological role of those neurons in the reflex responses elicited by hyperthermia needs to be investigated.

Diabetic nephropathy is the main cause for initiation of renal replacement therapy and early symptoms in patients include increased glomerular filtration rate (GFR), decreased oxygen tension and albuminuria, followed by a progressive decline in GFR and loss of kidney function. Experimental models of diabetes display increased GFR, decreased tissue oxygenation and nitric oxide bioavailability. These findings are likely to be intertwined in a mechanistic pathway to kidney damage and this thesis investigated their roles in the development of diabetic nephropathy. In vivo, diabetes-induced oxidative stress stimulates renal tubular Na+ transport and in vitro, proximal tubular cells from diabetic rats display increased transport-dependent oxygen consumption, demonstrating mechanisms contributing to decreased kidney oxygenation. In control animals, endogenous adenosine reduces vascular resistance of the efferent arteriole via adenosine A2-receptors resulting in reduced filtration fraction. However, in diabetes, adenosine A2-signalling is dysfunctional resulting in increased GFR via increased filtration fraction. This is caused by reduced adenosine A2a receptor-mediated vasodilation of efferent arterioles. The lack of adenosine-signaling in diabetes is likely due to reduced local adenosine concentration since adenosine A2a receptor activation reduced GFR only in diabetic animals by efferent arteriolar vasodilation. Furthermore, sub-optimal insulin treatment also alleviates increased filtration pressure in diabetes. However, this does not affect GFR due to a simultaneously induction of renal-blood flow dependent regulation of GFR by increasing the filtration coefficient. In diabetes, there is decreased bioavailability of nitric oxide, resulting in alterations that may contribute to diabetes-induced hyperfiltration and decreased oxygenation. Interestingly, increased plasma concentration of l-arginine, the substrate for nitric oxide production, prevents the development of increased GFR and proteinuria, but not increased oxygen consumption leading to sustained intra-renal hypoxia in diabetes. This thesis concludes that antioxidant treatment directed towards the NADPH oxidase as well maneuvers to promote nitric oxide production is beneficial in diabetic kidneys but is targeting different pathways i.e. transport-dependent oxygen consumption in the proximal tubule by NADPH oxidase inhibition and intra-renal hemodynamics after increased plasma l-arginine. Also, the involvement and importance of efferent arteriolar resistance in the development of diabetes-induced hyperfiltration via reduced adenosine A2a signaling is highlighted.

Diversos estudos epidemiológicos têm relacionado doenças na vida adulta, como diabetes tipo-2 e hipertensão, e ambiente inadequado durante a vida fetal. Fatores distintos relacionados aos hábitos alimentares, como ingestão de sal na dieta, podem ter impacto importante no período perinatal. Recentemente, demonstramos que dieta hipossódica (HO) durante a gestação está associada com baixo peso ao nascimento e alterações na vida adulta. O objetivo do presente estudo foi avaliar o efeito da dieta HO e hipersódica (HR) durante gestação em ratas. Ratas Wistar foram alimentadas com dieta HO, dieta normossódica ou HR desde a 8ª semana e foram acasaladas com 12 semanas de idade. Estes animais foram estudados na terceira semana de gestação e um grupo adicional de ratas virgens foi estudado como controle para o efeito da gestação. O peso da placenta e o do feto e o fluxo sangüíneo uterino foram menores e a resistência vascular periférica foi maior no grupo HO. Maior peroxidação lipídica e expressão gênica do receptor AT1 na placenta foram observadas no grupo HR. Em conclusão, peso do feto, peso da placenta e fluxo sangüíneo uterino são influenciados pelo consumo de sal durante a gestação.
Many epidemiological studies have linked diseases in adulthood, such as type-2 diabetes and hypertension, to adverse intrauterine environment during fetal life. Distinct factors related to dietary habits, such as salt intake, may have a major impact on the perinatal period. Recently, we have demonstrated that low-salt diet (LSD) during pregnancy is associated with low birth weight and diseases during adulthood. The aim of this study was to evaluate the effect of LSD and high-salt diet (HSD) during pregnancy in rats. Female Wistar rats were fed with LSD, normal-salt diet or HSD since 8 weeks of age and matted with 12 weeks of age. These animals were studied at the third week of gestation and one additional group of virgin rats was evaluated as a control for the gestation effect. Placenta and fetus weight and uterine blood flow were lower and peripheral vascular resistance was higher in the LSD group. In the placenta from HSD rats, higher lipid peroxidation and AT1 receptor mRNA were observed. In conclusion, fetal weight, placenta weight and uterine blood flow are influenced by the degree of salt consumption during pregnancy.

An 23 wachen Ratten wurde die dynamische Regulation der Nierengefäße als Antwort auf schwingungsförmige Änderung des renalen Perfusionsdruckes (RPP) gemessen. Es wurden der Renale Perfusionsdruck (RPP), der Nierenarterienfluss (RBF) sowie lokale Gefäßflüsse der Nierenrinde und des äußeren Nierenmark (Laser-Doppler) aufgezeichnet und daraus die entsprechende Conductance (Leitwert) der Gefäße errechnet. Der mittlere RPP wurde rampenförmig mit einer langsamen Änderungsrate gesenkt (dp/dt), wobei nach jeder absteigenden Flanke eine aufsteigende Rampe gleicher Geschwindigkeit gemessen wurde. Eine Überlagerung des RPP mit Schwingungen unterschiedlicher Frequenz (f=0,005, f=0,01 und f=0,02 Hz) bei einer Amplitude von 20 mmHg führte zu einem Anstieg von dp/dt und einem erhöhten Shearstress an der Gefäßwand (WSS). Der Einfluss der Schwingungen auf RCV war signifikant abhängig vom mittleren RPP. So war die Conductance in tieferen Druckbereichen des RPP mehrfach höher als in den Ausgangsdruckwerten. Innerhalb der absteigenden Rampen führte ein Erhöhung der Frequenz zu einem Anstieg der maximalen Amplitude des RVC des Nierengesamtflusses. Die größten Amplituden wurden bei RPP Werten zwischen 58 und 46 mmHg gemessen. Diese Abhängigkeit war bei den ansteigenden Flanken nicht gegeben. Außerdem zeigte sich in den abfallenden Versuchsteilen ein plötzlicher Phasenwechsel zwischen der RPP- und der RVC-Schwingung bei mittleren RPP-Werten zwischen 95 und 80 mmHg. Dies lässt schließen, dass oberhalb dieses Druckwertes aktive myogenen Vasokonstriktion die passiven Gefäßdilatation vollständig ausgleicht, während unterhalb dieses RPP-Wertes die Vasokonstriktion insuffizient reagiert, bis bei ca. 50 mmHg die RCV ausschließlich der passiven Vasodilatation folgt. Höhere Schwingungsfrequenzen führen durch einen Anstieg des WSS zu einer Erhöhung der Amplitude des RVC. Dies bewirkt eine Änderung der charakteristischen renalen Autoregulation des RPP. Auf diese Weise ändert sich die Effizienz der Autoregulation.
In 23 conscious rats, the dynamic features of renal vascular conductance (RVC) in response to oscillatory changes in renal perfusion pressure (RPP) were studied at different mean RPPs. RPP, renal blood flow, and regional cortical and outer-medullary fluxes (laser-Doppler) were continuously recorded and the respective RVCs calculated. Mean RPP was changed ramp-wise with a low rate of change (dp/dt), whereby a decremental ramp was immediately followed by an incremental ramp. Superimposing RPP oscillations (amplitude 20 mmHg) of different frequencies (f=0.005, f=0.01, and f=0.02 Hz) increased maximum dp/dt, and thus increased vascular wall shear stress (WSS). The impact of RPP oscillations on RVC critically depended on mean RPP. RVC oscillations were several times higher at lower mean RPPs than at control RPP During the decremental ramps, increasing the frequency led to an increase in the maximum amplitude of total RVC, and decreased mean RPP where maximum amplitude occurred from 58 to 46 mmHg. This frequency dependence was abolished during incremental ramps. Lowering mean RPP resulted in a sudden reversal of phase between RPP and RVC oscillations at mean RPP between 95 and 80 mmHg. It is concluded that, above this RPP, myogenic vasoconstriction fully counterbalances passive vasodilatation, whereas, below that RPP, myogenic constriction gradually tapers off until, at about 50 mmHg, RVC is exclusively determined by passive dilation. Higher oscillatory frequencies, assumed to be due to increased WSS, elicit a greater response in RVC amplitude as an expression of vessel compliance, and, thus change the RPP characteristics of renal autoregulation. However, the efficiency of autoregulation is thereby barely changed.

La sténose de l’artère rénale (SAR) est à l’origine d’une néphropathie dite « ischémique », dont les mécanismes conduisant au développement d’une insuffisance rénale sont mal connus. Il est utile de savoir à partir de quel degré de SAR surviennent des modifications hémodynamiques significatives dans le rein d’aval, et si une SAR chronique et hémodynamiquement significative peut entraîner une hypoxie rénale. Nous avons donc entrepris 2 études afin de préciser le lien entre degré de SAR et baisse du débit sanguin rénal (DSR), et de rechercher l’apparition d’une hypoxie dans le rein situé en aval d’une SAR chronique. Les résultats de la première étude montrent que la baisse du DSR reste modeste tant que le degré de SAR n’a pas dépassé 70%. Ces résultats nous permettent de conclure qu’une SAR de degré inférieur à 70% n’est probablement associée qu’à des modifications hémodynamiques mineures dans le rein d’aval. Dans la deuxième étude, nous avons décrit l’évolution du contenu rénal en oxygène (CRO) sur une période de 4 semaines après induction d’une SAR chez des rats. La méthode utilisée était l’IRM BOLD, qui permet d’étudier le CRO de manière non-invasive en mesurant le paramètre R2* dont la valeur est inversement proportionnelle au CRO. La mesure hebdomadaire de R2* dans le cortex, la médullaire externe et la partie externe de la médullaire externe des reins sténosés et des reins controlatéraux ne variaient pas au cours de l’étude, malgré l’apparition progressive d’une atrophie des reins en aval de la SAR. Ces données tendent à montrer qu’il n’y a pas d’hypoxie rénale dans notre modèle, et que l’atrophie rénale observée n’est donc pas secondaire à l’hypoxie
Renal artery stenosis (RAS) can lead to a so-called “ischemic” nephropathy but the mechanisms responsible for the development of chronic kidney disease in kidney downstream the RAS are largely unknown. There is an interest to know the degree of RAS that involves significant hémodynamic changes in the downstream kidney and if hypoxia occurs in this case. Therefore, we have undertaken two studies in order to describe the link between RAS degree and renal blood flow (RBF) and to search for the development of renal hypoxia in kidney downstream the RAS. Findings of the first study were that only a minor decrease of RBF occurs until the RAS degree reach 70%. We can thus conclude from these results that RAS degree must be at least of 70% to have hemodynamical repercussions in downstream kidney. In the second study, we describe the evolution of renal oxygen content (ROC) before and during 4 weeks after the constitution of RAS. ROC was measured weekly by the MRI BOLD technique, who allows to study ROC non-invasively by measuring the parameter called R2* that is inversely proportional to ROC. The value of R2* in the cortex, the outer medulla and the outer stripe of outer medulla in stenotic kidneys and controlateral kidneys was unchanged instead the development of atrophy of the kidney downstream the RAS. These results suggest that no renal hypoxia occur in this model and that renal atrophy is not caused by hypoxia

Peripheral vascular grafts are used for the treatment of peripheral arterial disease and arteriovenous grafts for vascular access in end stage renal disease. The development of neo-intimal hyperplasia and thrombosis in the distal anastomosis remains the main reason for occlusion in that region. The local haemodynamics produced by a graft in the host vessel is believed to significantly affect endothelial function. Single spiral flow is a normal feature in medium and large sized vessels and it is induced by the anatomical structure and physiological function of the cardiovascular system. Grafts designed to generate a single spiral flow in the distal anastomosis have been introduced in clinical practice and are known as spiral grafts. In this work, spiral peripheral vascular and arteriovenous grafts were compared with conventional grafts using ultrasound and computational methods to identify their haemodynamic differences. Vascular-graft flow phantoms were developed to house the grafts in different surgical configurations. Mimicking components, with appropriate acoustic properties, were chosen to minimise ultrasound beam refraction and distortion. A dual-beam two-dimensional vector Doppler technique was developed to visualise and quantify vortical structures downstream of each graft outflow in the cross-flow direction. Vorticity mapping and measurements of circulation were acquired based on the vector Doppler data. The flow within the vascular-graft models was simulated with computed tomography based image-guided modelling for further understanding of secondary flow motions and comparison with the experimental results. The computational assessments provided a three-dimensional velocity field in the lumen of the models allowing a range of fluid dynamic parameters to be predicted. Single- or double-spiral flow patterns consisting of a dominant and a smaller vortex were detected in the outflow of the spiral grafts. A double- triple- or tetra-spiral flow pattern was found in the outflow of the conventional graft, depending on model configuration and Reynolds number. These multiple-spiral patterns were associated with increased flow stagnation, separation and instability, which are known to be detrimental for endothelial behaviour. Increased in-plane mixing and wall shear stress, which are considered atheroprotective in normal vessels, were found in the outflow of the spiral devices. The results from the experimental approach were in agreement with those from the computational approach. This study applied ultrasound and computational methods to vascular-graft phantoms in order to characterise the flow field induced by spiral and conventional peripheral vascular and arteriovenous grafts. The results suggest that spiral grafts are associated with advanced local haemodynamics that may protect endothelial function and thereby may prevent their outflow anastomosis from neo-intimal hyperplasia and thrombosis. Consequently this work supports the hypothesis that spiral grafts may decrease outflow stenosis and hence improve patency rates in patients.

Introduction of Doppler ultrasound techniques into the Intensive Care setting has revolutionised the way haemodynamic status is monitored in the critically ill. However, in order to increase the usefulness of these techniques, the Doppler signal and its spectrum need to be further analysed in ways to facilitate a better clinical response. Extensive processing of the Doppler spectrum on Diagnostic ultrasound machines is limited by the real time performance considerations. It was therefore proposed that the spectral information from these systems be extracted off-line and full set of analytical tools be made available to evaluate this information. This was achieved by creating an integrated and modular software tool called Spectron, which was intended as an aid in the overall management of the patients. The modular nature of Spectron was intended to ensure that new analytical tools and techniques could be easily added and tested. The software provides its users with considerable latitude in choosing various data acquisition and analysis parameters to suit various clinical situations and patient requirements. Spectron was developed under the Windows environment to provide a user friendly interface and to address a range of programming problems such as memory management and the size of the colour palettes. Spectron is able to detect the maximal velocities and compute the mean and median velocities. Relative increases in maximal velocities in cardiac blood flows after the administration of inotropic drugs have been shown in the pilot studies that were conducted. Spectron is able to help in obtaining estimates of the aortic blood flows and in other applications such measuring vascular impedance. Stenotic blood flows can be detected by using the spectral broadening index and blood flow characteristics can be studied by using various blood flow indices. Thus, this project attempted to help in patient management by providing clinicians with a range of blood flow parameters and has succeeded in meeting its objective to a large extent
Master of Engineering (Hons)

A system comprising of a personal microcomputer and a Digital Signal Processor board has been assembled and programmed for real-time spectral analysis of Doppler ultrasound signals. Three spectrum analysis techniques were implemented to run in real-time on the system: The fast Fourier transform (FFT), the autoregressive (AR) model, and the moving average (MA) model. The FFT and the AR techniques were investigated in some depth. The advantages of using such a system are that it is entirely programmable, cheap, reliable, and that the processed information can be stored on diskettes. The inputs to the system are the forward and reverse components of the Doppler ultrasonic signal, and the outputs are the sonogram, the frequency envelope, and the intensity weighted mean frequency curve, which are presented on the screen and can be saved to diskette. Five frequency ranges can be selected by the operator, from 1.28 kHz to 20.48 kHz, corresponding to sampling frequencies from 2.56 kHz to 40.96 kHz. Most commercial systems for real-time spectral analysis of Doppler ultrasonic signals implement the modified FFT-periodogram technique for power spectral density estimation (PSDE), which is computationally very efficient but has some shortcomings, especially for the analysis of relatively short records. With the AR model approach the spectra can be estimated from short segments, no antileakage window is necessary and the spectral resolution is better than for the FFT. A study of some methods for order selection used with the autoregressive model for the spectrum analysis of Doppler signals is reported and the use of a fixed order of around 12 is suggested for the AR model. The implementation of the AR PSDE approach in real-time, in a reasonably priced system, is a step towards the practical use of the so called 'modern techniques' for spectral analysis of Doppler ultrasonic signals, but further work has to be done on the validation of the technique in clinical usage.

The goals of the work described here were the development of a method of selection of spectral estimation for use with pulsed Doppler ultrasonic blood flow instruments, and the use of this method to select an estimator and its implementation in a form suitable for real-time applications. A study of estimation accuracy of the mean frequency and bandwidth using a number of spectral estimators was carried out. Fourier based, parametric, and, minimum variance estimators were considered. A Doppler signal simulator was developed to allow the accuracy tests required. A method of selection of spectral estimators based on the accuracy of estimation of decisive signal parameters, under the constraint of low computational complexity has been proposed. This novel cost/benefit criterion, allows the possibility of weighting appropriate to estimator (mean frequency and bandwidth) and signal frequency importance (across the range of signal characteristics). For parametric spectral estimators, this criterion may also be used to select model order, leading to lower orders than FPE, AIC and CAT criteria. Its use led to the selection of a 4t' order modified covariance parametric method. A new version of the modified covariance method for spectral estimation of real signals was developed. This was created with a view to the parallel partitioning of the algorithm for parallel implementation on a transputer-based system, using OCCAM. A number of parallel topologies were implemented. Their performance was evaluated considering estimation of a single, and a sequence of Doppler signal segments, revealing the feasibility of these parallel implementations to be achieved in real-time.

Renal sympathetic nerve activity (RSNA) plays an important role in the control of renal hemodynamics and function. It achieves this control by changing the mean levels of activity and/or changing the power of the distinct frequencies that comprise this mean activity. My studies, presented in four parts, investigate how total renal blood flow (RBF) and intrarenal blood flow are controlled by these changes in RSNA. While RSNA and RBF both show oscillations at various frequencies, the functional significance and regulation of these oscillations is not well understood. To establish whether the strength of these oscillations is under differential control I measured the frequency spectrum of RSNA and RBF following volume expansion in conscious rabbits. At least 6 days prior to experiments animals underwent surgery to implant an electrode for recording renal nerve activity and a flow probe for recording RBF. Volume expansion resulted in a 25 ± 5% decrease in mean RSNA, paralleled by an increase in RBF. Renal denervated rabbits did not show an increase in RBF with volume expansion. Spectral analysis of the different frequencies in RSNA showed oscillations in RSNA between 0.2 to 0.4 Hz were selectively decreased following volume expansion (14 ± 3 to 6±1% of total power in RSNA at < 3Hz). A corresponding decrease in the strength of oscillations in RBF at this frequency was also seen (20 ± 6 to 8 ± 2%). In contrast the strength of respiratory (0.8 to 2.0 Hz) and cardiac (3 to 6 Hz) related rhythms did not change with volume expansion. These results show that selective changes in the different frequency components of RSNA can occur. While RSNA plays a significant role in the regulation of RBF, little is known about the role renal nerves may play in the control of regional kidney blood flows i.e. cortical and medullary blood flow (CBF and MBF respectively). This is an important question as the control of blood flow to the renal medulla has been shown to be critical in the long-term control of arterial pressure, chiefly through its influence on tubular reabsorption of salt and water. If renal nerves are involved in the control of medullary blood flow then they may also have a role in long-term arterial pressure regulation. My aim was to investigate the role RSNA may have in the regulation of both CBF and MBF. In a series of experiments, using pentobarbitone anaesthetized rabbits, I electrically stimulated the renal nerves whilst simultaneously recording RBF, CBF, and MBF. Three sequences of stimulation were applied, 1) varying the amplitude of stimulation, 2) varying the frequency of stimulation and 3) stimulation with a modulated sinusoidal pattern which allows determination of the frequency response characteristics of each flow. Increasing amplitude or frequency of stimulation progressively decreased all flow variables. RBF and CBF responded similarly, but MBF responded less. For example, 0.5 V stimulation decreased CBF by 20 ± 9% but MBF fell by only 4 ± 6%. The amplitude of oscillations in all flow variables was progressively reduced as the frequency of sinusoidal stimulation was increased. An increased amplitude of oscillation was observed at 0.12 and 0.32 Hz in MBF, and to a lesser extent RBF, but not CBF. MBF therefore appears to be less sensitive than CBF to the magnitude of RSNA, but more able to respond to these higher frequencies of neural stimulation. These results show that regional renal blood flows may be differentially regulated by RSNA and indicate a role for RSNA in the control of MBF. To further investigate the effects of RSNA on intrarenal blood flow I performed another series of experiments in which I reflexly increased RSNA while simultaneously recording CBF and MBF. I exposed pentobarbitone anesthetized, artificially ventilated rabbits to graded reductions in inspired 02 content. A separate group of animals with denervated kidneys underwent the same protocol. Graded hypoxia (16, 14, 12 and 10% inspired 02) progressively reduced arterial 02 partial pressure and increased RSNA (by 8 ± 3, 44 ± 25, 62 ± 21 and 76 ± 37% respectively compared with air) without affecting MAP. This was accompanied by progressive reductions in CBF (by 2 ± 1, 5 ± 2, 11 ± 3 and 14 ± 2% respectively) in intact but not denervated rabbits. MBF was unaffected by hypoxia in either group. Thus, reflex increases in RSNA cause renal cortical vasoconstriction, but not at vascular sites regulating MBF. Taken together results from both these studies provide strong evidence that MBF is less sensitive to the vasoconstrictor influence of RSNA than is CBF. However, larger, chronic increases in RSNA, such as occur in heart failure, could be associated with decreases in MBF. This may implicate RSNA in the long-term control of arterial pressure. The 0.3 Hz oscillation in RSNA, and thus MAP, is intermittent in its presence. In a final series of experiments I studied the underlying reasons for the presence or absence of the 0.3 Hz oscillation. Using conscious animals I studied the oscillation under a range of sympathetic stimulants. I was unable to induce an oscillation in MAP at 0.3 Hz and propose reasons for this. To allow further analysis, I performed a second set of experiments in which I induced the oscillation in RBF by electrical stimulation of the aortic depressor nerve. I found that large amplitude oscillations in baroreceptor stimulation were required to induce oscillations in RBF and MAP. I speculate on what this may tell us about the nature of the slow oscillation.

The aim of this project is to test the hypothesis that the rate of renal blood flow remains constant under normal physiological conditions. Methods were developed for long term studies of renal blood flow (using the Doppler flow probe) and blood pressure in the conscious unrestrained rat. Special care was taken to maintain and observe the rats under normal, physiological conditions. Since the Doppler flow probe measures blood velocity rather than flow, changes in renal arterial diameter will alter the output of the flow meter, even if flow is constant. In order to measure flow more accurately, chanqes in vessel diameter were prevented by a short length of silastic tubing inserted into the renal, ortery under the probe. Blood flow was expressed as a percentage of the maximal flow measured when the animal was completely relaxed. Using this preparation, renal blood flow was measured continuously under normal conditions in both the light and dark cycles. Studies were performed to assess the effects on renal blood flow of anaesthesia, surgery and stress, and to assess the effect on renal blood flow of blockade of the renal nerves. Renal blood flow was depressed approximately 50% by anaesthesia, due to the effects of the anaesthetic agent rather than the accompanying surgery. Renal blood flow did not fully recover for 3-4 days after anaesthesia with, or without surgery. Renal blood flow was depressed by stress, even though blood pressure was unchanged. A mild sudden auditory disturbance caused a transient 23% fall in renal blood flow. A continuous auditory disturbance, depressed renal blood flow by 16% for several minutes. Handling the rat resulted in a 33% fall in renal blood flow which lasted for over 30 minutes. When measured continuously, renal blood flow was found to vary considerably. When the rat was completely relaxed renal blood flow was highest (defined as 100%). Renal blood flow remained high when eating and drinking (79%), but fell when the rat became alert but completely still (74%). During general movement renal blood flow was low (73%) with flow lowest while grooming (64%). Flow was apparently related to the degree of alertness and to activity. The extent of variation of flow is such that the calculated mean daily value of renal blood flow was only 80% of the maximum flow observed during complete relaxation. The depression of renal blood flow seen during activity and disturbance was largely prevented during reversible blockade of the ipsilateral renal nerve, induced by slow infusion of xylocaine around the renal artery. It was completely abolished by bilateral renal nerve blockade with Xylocaine. The depressive effects of activity and disturbance on renal blood flow were restored an hour after the Xylocaine infusion ceased. These studies clearly show that renal nerve is involved in control of renal blood flow under physiological conditions. It is clear that renal blood flow varies markedly under normal physiological conditions and in response to the external environment. A constant renal blood flow is not a necessity for normal renal function.

The relative contributions of angiotensin II (ANG II) and bradykinin (BK) to the renal regional blood flow responses during angiotensin converting enzyme (ACE) inhibition remain unclear. The overall aim of the investigation reported in this thesis was to evaluate the renal regional vasodilatory responses ACE inhibition in dogs fed on a normal salt diet as well as on a low salt diet in order to achieve a condition of activated renin-angiotensin and kallikrein-kinin systems. As ACE inhibition is known to cause reductions in angiotensin II (ANG II) formation as well as decreases in bradykinin (BK) degradation, the relative contributions of these two mechanisms in the renal vasodilatory responses to ACE inhibition was evaluated in these studies. Relative changes in renal cortical (CBF) and medullary (MBF) blood flows were determined using laser Doppler flowmetry (LDF) with two needle probes placed in the mid-cortical and mid-medullary regions of the kidney respectively. Total renal blood flow (RBF) was measured with an electromagnetic flow probe placed around the renal artery. Responses to intraarterial administration of the ACE inhibitor enalaprilat (33 mug/kg/min) were assessed in the presence and absence of the bradykinin B2 receptor blocker, icatibant (100--300 mug, intravenous administration) in both groups of dogs (normal salt and low salt fed groups). In dogs fed a normal salt diet (n = 14), ACE inhibition resulted in increases in CBF (23 +/- 2%), MBF (33 +/- 9%), and RBF (44 +/- 5%). B2 receptor blockade either before or after ACE inhibition did not significantly affect these vasodilatory responses. However, in the dogs fed a low salt diet, the blood flow responses to ACE inhibition could be significantly attenuated by prior blockade of B2 receptors. As systemically formed ANG II could influence the responses to intrarenal administration of enalaprilat in these B2 receptor blocked dogs, additional experiments were performed to examine these responses in dogs fed a low salt diet (n = 7), in the presence of the ANG II AT 1 receptor blocker, candesartan (100 ng; intraarterial bolus administration). In these studies, although candesartan significantly increased total as well as regional blood flows (RBF: +21 +/- 5%, CBF: +20 +/- 2%, MBF: +22 +/- 7%). ACE inhibition in the presence of AT1 receptor blockade resulted in further increases in RBF (+24 +/- 6%), CBF (+21 +/- 5%) and MBF (+41 +/- 8%). It was also noted that the relative changes in MBF were significantly greater than those in CBF (+41 +/- 8% vs. +21 +/- 5%, P < 0.01), during ACE inhibition in candesartan treated dogs. Administration of the BK B2 receptor blocker icatibant (300mug) following enalaprilat returned RBF, CBF and MBF to values seen with AT 1 receptor blockade alone. The results of this investigation support a substantive role for BK potentiation in mediating ACE inhibitor-induced renal vasodilation in dogs maintained on a low sodium diet. These data also demonstrate a relatively greater role of BK potentiation during ACE inhibition in the regulation of MBF compared to that of CBF
acase@tulane.edu

Dissertação de mestrado integrado em Engenharia Biomédica
As doenças cardiovasculares são um problema de saúde com elevada incidência na população mundial. Desta forma, a caracterização do fluxo sanguíneo é uma importante estratégia para estabelecer uma relação entre o comportamento hemodinâmico e a ocorrência de doenças cardiovasculares. As complexas propriedades do fluxo sanguíneo, tornam-se ainda mais evidentes quando associadas a doenças cardiovasculares. A aterosclerose é a doença cardiovascular mais comum nas artérias, esta caracteriza-se pela deposição de placas nas paredes internas das artérias, levando à redução da área de secção transversal, denominada por estenose. Esta redução, pode produzir um impacto significativo no fluxo sanguíneo. O objetivo do presente trabalho, é o estudo numérico das propriedades hemodinâmicas da aorta abdominal ao nível da bifurcação renal, através da implementação de diferentes condições de escoamento. Esta região é um local propicio ao desenvolvimento de aterosclerose, levando a uma diminuição da corrente sanguínea, e consequentemente a problemas, como a hipertensão. As simulações foram realizadas utilizando, ANSYS FLUENT®, um software que emprega o método dos volumes finitos. Esta ferramenta permite avaliar a distribuição dos perfis de velocidade e tensões de corte na parede durante o ciclo cardíaco para os diferentes casos estudados. Neste estudo, foram analisadas as diferenças existentes na hemodinâmica quando se considera o sangue como um fluido newtoniano, mas com um escoamento laminar e com um escoamento turbulento, utilizando-se os modelos: k-ɛ, o k-ω SST e o Reynolds Stress. Posteriormente, examinaram-se as principais diferenças existentes na hemodinâmica quando se considera o sangue como um fluido newtoniano e como um fluido não-newtoniano, utilizando-se o modelo de Carreau. Os resultados obtidos permitiram identificar a influência dos diferentes modelos de turbulência no escoamento sanguíneo, indicando que o modelo k-ω STT seria o mais adequado. Para o modelo newtoniano e não-newtoniano, as diferenças são apenas mais evidentes para velocidades mais baixas, no entanto o modelo não-newtoniano deve ser utilizado para estudos do escoamento sanguíneo.
The cardiovascular diseases are a main health problem, with high incidence in the world population. Therefore, blood flow characterization is an important strategy to establish a relationship between the hemodynamic behavior and the appearing of cardiovascular pathologies. The complex properties of the blood flow, become even more evident when associated with vascular diseases. Atherosclerosis is the most common cardiovascular disease in arteries, leading to the reduction of the cross-sectional area, called stenosis. This reduction, is capable to induce a huge impact on the normal blood flow. The objective of the present work, is the study of hemodynamic properties on the abdominal aorta at the renal bifurcation region, through the implementation of different flow conditions. The renal arterial region is of high interest, once the development of atherosclerosis is recurrent, and may lead to renal problems, namely renal failure or to hypertension. The simulations were made using, ANSYS FLUENT ®, a software that uses the method of finite volumes. This tool allows to evaluate the distribution of the velocity and wall shear stress profiles, during a cardiac cycle for the diverse cases under study. In this investigation, were analyzed the existing differences on the hemodynamic, considering the blood as a Newtonian fluid, with a laminar flow and also with a turbulent flow, using the k-ɛ model, k-ω SST model and the Reynolds Stress model. Posteriorly, were examined the variances on the hemodynamic when considering now the blood flow as a Newtonian fluid and as a non-Newtonian fluid, using the Carreau model. The obtained results allowed to identify the influence of the different turbulence models on the blood flow, denoting that the k-ω SST model seems to be the more indicated. Between the Newtonian and the non-Newtonian flow models, the differences were more evident for lower velocities. On the other hand, the non-Newtonian model must be used for the study of the blood flow.

碩士
國立成功大學
電機工程學系碩博士班
91
Chinese Medicine was innovated earlier than Modern Medicine. It is a bible of Chinese civilization in medicine. Chinese Medicine originated from Chinese people’s intelligence. And it has taken care of Chinese health generation by generation for thousands years. Recently, a resonance model of blood pressure circulation was presented by professor W.K. Wang. He considers that top ten of diseased death is related to blood circulation and the main cause is obstructive in blood circulation. This study develops a system with the function of real-time measuring, recording and analyzing the variation of peripheral blood flow waveform. The result is used to estimate the relation between blood circulation and physiological condition. It can be offer a reference for a medical doctor.

碩士
國立臺灣大學
機械工程學研究所
106
In this thesis, we proposed a real-time blood-flow-monitoring system with the merits of being portable and easy-to-operate for medical emergency applications. This device was designed to measure the patients’ blood pressures and arterial blood flow velocities via a non-invasive measuring approach. In most circumstances of performing cardiopulmonary resuscitation (CPR) to cardiac arrest patients, rescuers are required to palpate the patients’ carotid arteries to detect the recovery status. However, this method is unreliable due to the lack of quantitative standards and frequent misjudgments. Therefore, based on the characteristics of human blood circulation system, we adopt photoplethysmogram (PPG) sensors, a new design of piezoresistive arterial pulse sensors (APS), the signal processing circuits, and heartbeat waveform analyzing algorithms. By integrating these technics, we proposed a device that measured peripheral pulse wave velocities (PWV) at hands and necks of humans. We furthermore measured blood pressures and blood flow velocities from different subjects and analyzed the relations. In conclusion, we presented a non-invasive real-time blood-flow-monitoring system and it is expected to be integrated with the current emergency devices for practical medial resuscitations.

The increasing incidence of children suffering from allergic diseases could be caused by sensitization of immature immune system during the intrauterine development. Several important scientific papers have demonstrated the ability of cord blood cells to respond by elevated proliferation activity after stimulation by common allergens. Following these findings, present study follows the production of cytokines which play a role in the pro- and anti-allergenic tuning of the immune system. Umbilical cord blood cells were stimulated with polyclonal activators (phytohaemagglutinin) and common allergens (ovalbumin, timothy grass, birch, mite). Subsequently, cytokine production was monitored using selected methods that reflect different stages of cell activation - at the level of mRNA by quantitative real time PCR (qRT-PCR), by flow cytometry detection of the presence of intracellular cytokines in different cell subpopulations and by ELISA measurement of cytokines in CBMC culture supernatants. The results obtained point to a very weak ability of these common allergens (timothy grass, birch, mite, ovalbumin) to stimulate CBMC to produce cytokines observed by all of these methodological procedures. Although we did not observe significant differences in CBMC cytokine production (IL-2, IL-4, IL-10, IL-12,...

The prevalence of allergy is increasing and it is becoming a serious problem not on- ly in medicine, but also in social and economic terms. The most effective way to minimize the development of allergic diseases is preventive measures. In recent years, many studies have attempted to confirm or rebut the hypothesis that early administration of probiotic bacteria to newborns and pregnant women before birth could have preventive effects on the development of allergy. In the Czech Republic, the probiotic strain Escherichia coli O83:K24:H31 (EC O83), being registered with the State Health Institute for Drug Control under the name Colinfant Newborn, has long been used to prevent allergies and paediatri- cians have long been known and used it against various diarrhoea. The aim of this work was to elucidate the effect of EC O83 on CBMC (cord blood mononuclear cells) and to compare the ability of CBMC of healthy mothers (children with a relatively low risk of developing allergic disease) and allergic mothers (children at high risk of developing allergies) to form cytokines in response to EC O83 stimulation. Phytohemagglutinin was used as a positive control, Escherichia coli Nissle 1917 was used as a reference probiotic strain, which is much more known abroad than EC O83. Cytokine production was detected by...