Addenda and corrigenda inserted on verso of back end paper. Includes: Publications and communications to learned societies (p. 4-5). Bibliography: leaves 272-286. Examines the acute myocardial uptake of drugs, particularly perindoprilat and enalaprilat in humans. The uptake of these agents is examined, together with the haemodynamic, metabolic and biochemical effects. In particular, the impact of these agents on angiotensin and bradykinin peptides both within the heart and peripherally is described. The acute effects of a range of cardioactive drugs upon the left ventricular force-interval relationship is examined.

Addenda and corrigenda inserted on verso of back end paper. / Includes: Publications and communications to learned societies (p. 4-5). / Bibliography: leaves 272-286. / 286 leaves : ill. ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Examines the acute myocardial uptake of drugs, particularly perindoprilat and enalaprilat in humans. The uptake of these agents is examined, together with the haemodynamic, metabolic and biochemical effects. In particular, the impact of these agents on angiotensin and bradykinin peptides both within the heart and peripherally is described. The acute effects of a range of cardioactive drugs upon the left ventricular force-interval relationship is examined. / Thesis (Ph.D.)--University of Adelaide, Dept. of Medicine, 1999

No description available.

No description available.

Accompanying diskette contains data of Chapters 3, 4, 5, 7, 8 and 9 (ASCII) / Bibliography: leaves 177-207. / xiv, 208, [93] leaves : ill. ; 30 cm. + 1 computer disk (2 sided, double density ; 3 1/2 in.) / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Defines myocardial pharmacokinetic profiles using mass balance principles and correlates them with simultaneously measured myocardial pharmacodynamic profiles. / Thesis (Ph.D.)--University of Adelaide, Dept. of Anaesthesia and Intensive Care, 1992

Thesis (MSc)--University of Stellenbosch, 2002. / ENGLISH ABSTRACT: Background: Athletes use androgenic anabolic steroids (AAS) to enhance their physical performance. The abuse of AAS is however associated with a host of side effects including sudden death due to cardiac arrest. The use of AAS leads to myocardial hypertrophy, which possibly makes the heart more prone to ischaemia/reperfusion injury, since it often develops in the absence of proper vasculature development. Chronic AAS use also disrupts myocardial p-adrenoreceptor function and possibly cAMP, signalling in the heart. Drugs increasing cAMP and decreasing cGMP levels in the ischaemic myocardium exacerbate myocardial ischaemia/reperfusion injury. We also know that AAS causes coronary artery disease secondary to the deleterious alteration of lipid profiles by increasing the LOL cholesterol and decreasing the HOLcholesterol levels. AAS treatment may increase systemic TNFa levels by stimulating lymphocyte TNFa secretion that has been implicated in the depression of myocardial function, myocardial hypertrophy and the worsening of ischaemia/reperfsuion injury. Aims: To determine whether chronic AAS treatment in trained and untrained rats influences: 1) heart function and susceptibility to ischaemia/reperfusion injury, 2) myocardial cyclic nucleotide levels (cAMP and cGMP) and 3) myocardial TNFa levels. Material and methods: Male Sprague-Dawley rats (n=100) were divided into 4 groups: sedentary vehicle (placebo) treated group, sedentary AAS treated group, exercise vehicle (placebo) treated group, and exercise AAS treated group. Steroid treated animals received an intramuscular injection of nandrolone laureate (0.375 mg/kg) once a week, for six weeks. Training consisted of swim sessions 6 days a week for 6 weeks. Swim time was incrementally increased up to a maximum of 50 minutes a day. For biometric parameters heart weight and body weight were documented. Hearts were mounted on a l.anqendorff perfusion apparatus and left ventricular developed pressure (LVDP), heart rate (HR) and coronary flow (CF) was monitored. The hearts were subjected to a period of 20 minutes of global ischaemia, followed by 30 minutes of reperfusion. Functional parameters was again monitored and documented. For biochemical analysis, blood was collected for the determination of serum lipid levels and myocardial tissue samples were collected before, during and after ischaemia for the determination of myocardial TNFa, cGMP and cAMP levels and p38 activity. Conclusions: Results obtained would suggest that AAS exacerbate exercise induced myocardial hypertrophy. It also prevents the exercise-induced improvement in cardiac function. AAS use reduces reperfusion function in treated hearts, which may suggest that AAS exacerbates ischaemie and reperfusion injury. Furthermore it was seen that AAS elevates basal (preischaemie) cyclic nucleotide levels and basal (pre-ischaemic) as well as reperfusion TNFa levels. This may also contribute to the exacerbation of ischaemic and reperfusion injury. / AFRIKAANSE OPSOMMING: Agtergrond: Androgeniese anaboliese steroïede (AAS) word dikwels deur atlete gebruik om sportprestasie te verbeter. Die misbruik van AAS het egter talle newe effekte, insluitende skielike dood wat gewoonlik toegeskryf word aan hartaanvalle. Die gebruik van AAS lei onder andere tot miokardiale hipertrofie wat opsigself, as gevolg van ontoereikende vaskulêre ontwikkeling tydens die ontwikkeling van hipertrofie, die hart nog meer vatbaar vir isgemie/herperfusie skade maak. Kroniese AAS toediening versteur miokardiale beta-adtenoresepter funksie en moontlik die tweede boodskapper, sAMP, seintransduksie in die hart. Ons weet ook dat AAS koronêre hartvatsiektes veroorsaak. Laasgenoemde is sekondêr tot die nadelige lipiedprofiel verandering, wat 'n verhoging in LDL-C en 'n verlaging in HDL-C insluit. Middels wat miokardiale sAMP vlakke verhoog en sGMP vlakke in die isgemiese miokardium verlaag, vererger miokardiale isgemie/herperfusie skade. AAS behandeling kan moontlik ook sistemiese TNFa vlakke verhoog deur limfosiet TNFa sekresie te stimuleer. Die verhoogde TNFa vlakke word verbind aan die onderdrukking van miokardiale funksie, miokardiale hipertrofie en die verergering van isgemie/herperfusie skade. Doelwitte: Die doelwitte van die studie was om te bepaal of kroniese AAS toediening in geoefende en ongeoefende rotte 1) hartfunksie en die hart se vatbaarheid vir isgemie/herperfusie skade beïnvloed, 2) miokardiale sikliese nukleotiedvlakke (sAMP en sGMP) beïnvloed en 3) miokardiale TNFa-vlakke beïnvloed. Materiale en metodes: Manlike Sprague-Dawley rotte (n=100) is gebruik en in 4 groepe verdeel: 'n ongeoefende placebo groep (kontrole); 'n ongeoefende steroïedbehandelde groep; 'n geoefende placebo groep (kontrole) en 'n geoefende steroïedbehandelde groep. Steroïed behandelde diere het 'n intramuskulêre nandroloon lauraat inspuiting (0.375 mg/kg) een keer per week vir ses weke ontvang. Die oefenprogram het bestaan uit ses swemsessies 'n week vir ses weke. Die swemtyd is geleidelik weekliks verhoog tot by 'n maksimum tyd 50 min. Die waterbadtemperatuur is tussen 30 - 32 oe gehandhaaf. Vir biometriese parameters is hartgewig en liggaamsgewig genoteer. Harte is op 'n Langendorff perfusie apparaat gemonteer en linker ventrikulêre ontwikkelde druk (LVOD), koronêre vloei (KV) en harttempo (HT) is genoteer. Die harte is vervolgens blootgestel aan 20 minute van globale isgemie gevolg deur 'n 30 minute herperfusieperiode. LVOD, KV en HT is weer eens noteer. Vir biochemiese doeleindes is bloed voor perfusie versamelom serum lipied vlakke te bepaal. Miokardiale weefsel is versamel voor, tydens en na isgemie vir die bepaling van TNFa, cGMP en AMP vlakke asook p38 aktiwiteit. Gevolgtrekkings: Na aanleiding van resultate verkry wil dit voorkom asof die gebruik van steroïde oefeningsgeïnduseerde miokardiale hipertrofie vererger. Dit verhoed ook oefeningsgeïnduseerde verbetering in miokardiale funksie. AAS lei tot 'n verlaagde herperfusiefunksie in behandelde harte, wat dalk mag dui op MS verergering van isgemie en herperfusie skade. Verder was daar ook waargeneem dat MS basale (pre-isgemiese) sikliese nukleotiedvlakke en basale TNFa-vlakke sowel as herperfusie TNFa vlakke verhoog. Die verhoging in TNF-a vlakke mag dus moontlik ook bydra tot die verergering van isgemie- en herperfusieskade.

Bibliography: leaves 306-353. / xiii, 353 leaves : ill. ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Utilizing a paired transcoronary sampling technique, serial determination of myocardial drug content was determined following intravenous bolus injection in patients undergoing diagnostic cardiac catheterization for the investigation of chest pain. There was significant modulation of haemodynamic effects of all three drugs according to changes in systolic interval. / Thesis (Ph.D.)--University of Adelaide, Dept. of Medicine, Queen Elizabeth Hospital, Cardiology Unit

No description available.

Resumo: A frequência de hipovitaminose D é alta na população. A deficiência de vitamina D tem sido considerada problema de saúde pública no Brasil e no mundo. Além disso, a deficiência dessa vitamina está associada com o aumento do risco de várias doenças crônicas. Assim, está ocorrendo uso indiscriminado de vitamina D sem conhecer ao certo seus efeitos adversos. Estudos mostraram que essa vitamina é importante para o desenvolvimento e funcionamento adequado do coração. A deficiência de vitamina D provoca remodelação cardíaca enquanto que a suplementação de vitamina D, em modelos de agressão, atenua a remodelação. Porém pouco se sabe sobre sua influência no coração normal. O objetivo foi verificar se a suplementação com diferentes doses de vitamina D3 na dieta promove remodelação cardíaca com alterações na estrutura, na função, no metabolismo energético e nos moduladores inflamatórios do coração normal de ratos Wistar. Para isso foram utilizados 86 ratos machos, alocados em quatro grupos: Controle (C, n=21) recebeu dieta padrão; 3D (n=22), 5D (n=22) e 10D (n=21) receberam 3.000, 5.000 e 10.000 UI de colicalciferol/kg de dieta respectivamente. Após dois meses foi realizada a pressão arterial caudal e o estudo ecocardiográfico. Os animais foram eutanasiados, o soro e o ventrículo esquerdo foram utilizados para análises bioquímicas. Para análise estatística foi realizado ANOVA de 1 via e pós teste de Tukey ou Kruskal Wallis e pós teste de Dunn. Para avaliar a resposta dose dependente foi utilizado o teste de tendência (correlação de Spearman). As concentrações séricos de cálcio e fósforo foram maiores no grupo 5D e 10D em relação ao C. A pressão caudal foi maior nos grupos 3D e 10D em relação ao C e apresentou aumento dose dependente. A concentração sérica de 25 (OH) D3 foi maior no grupo 5D em relação aos outros grupos e foi maior... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Frequency of hypovitaminosis D in population is high and vitamin D deficiency has been considered a public health problem. Moreover, Vitamin D deficiency is associated with increased risk of many chronic diseases. Thus, it is widespread use of vitamin D without knowing its adverse effects. Studies have shown that this vitamin is important for cardiac development and functioning. Vitamin D deficiency results in cardiac remodeling and vitamin D supplementation in cardiac aggression models attenuates cardiac remodeling. However, influence of vitamin D supplementation in normal rats is not completed known. The aim of this study was to evaluate whether supplementation with vitamin D3 results in cardiac remodeling with changes in structure, function, energy metabolism and inflammatory mediators in the heart of normal rats. We used 86 male rats allocated into four groups: control (C, n = 11) received standard diet; 3D (n = 12), 5D (n = 13) and 10D (n = 11) received 3000, 5000 and 10,000 IU of cholecalciferol / kg diet. After two months the animals were submitted to functional study, morphometric, and biochemical. For the statistical analysis was used the ANOVA test of variance complemented by Tukey, the test Kruskal Wallis complemented by Dunn. To evaluate the dose response was used the Spearman correlation. Serum calcium and phosphorus were higher in the 5D and 10D in relation to the group C. The blood pressure was higher in the groups 3D and 10D in relation to the group C. The increase in blood pressure was dose dependent. Serum 25 (OH) D3 was higher in the group 5D in relation to the other groups and it was higher in the group 10D in relation to the group C. There were no differences in echocardiographic variables of morphology and function. The activity of the enzyme β hydroxyacyl coenzyme A dehydrogenase was smaller in the groups 5D and 10D in relation to other groups... (Complete abstract click electronic access below) / Orientador: Sérgio Alberto Rupp de Paiva / Coorientador: Leonardo A. M. Zornoff / Banca: Marcelo Macedo Rogero / Banca: Paula Schmidt Azevedo Gaiola / Mestre

Made available in DSpace on 2014-06-11T19:25:36Z (GMT). No. of bitstreams: 0 Previous issue date: 2011-02-28Bitstream added on 2014-06-13T18:53:45Z : No. of bitstreams: 1 santos_pp_me_botfm.pdf: 349987 bytes, checksum: 913fc9a75063c45bd784ef00c6dc221f (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / A frequência de hipovitaminose D é alta na população. A deficiência de vitamina D tem sido considerada problema de saúde pública no Brasil e no mundo. Além disso, a deficiência dessa vitamina está associada com o aumento do risco de várias doenças crônicas. Assim, está ocorrendo uso indiscriminado de vitamina D sem conhecer ao certo seus efeitos adversos. Estudos mostraram que essa vitamina é importante para o desenvolvimento e funcionamento adequado do coração. A deficiência de vitamina D provoca remodelação cardíaca enquanto que a suplementação de vitamina D, em modelos de agressão, atenua a remodelação. Porém pouco se sabe sobre sua influência no coração normal. O objetivo foi verificar se a suplementação com diferentes doses de vitamina D3 na dieta promove remodelação cardíaca com alterações na estrutura, na função, no metabolismo energético e nos moduladores inflamatórios do coração normal de ratos Wistar. Para isso foram utilizados 86 ratos machos, alocados em quatro grupos: Controle (C, n=21) recebeu dieta padrão; 3D (n=22), 5D (n=22) e 10D (n=21) receberam 3.000, 5.000 e 10.000 UI de colicalciferol/kg de dieta respectivamente. Após dois meses foi realizada a pressão arterial caudal e o estudo ecocardiográfico. Os animais foram eutanasiados, o soro e o ventrículo esquerdo foram utilizados para análises bioquímicas. Para análise estatística foi realizado ANOVA de 1 via e pós teste de Tukey ou Kruskal Wallis e pós teste de Dunn. Para avaliar a resposta dose dependente foi utilizado o teste de tendência (correlação de Spearman). As concentrações séricos de cálcio e fósforo foram maiores no grupo 5D e 10D em relação ao C. A pressão caudal foi maior nos grupos 3D e 10D em relação ao C e apresentou aumento dose dependente. A concentração sérica de 25 (OH) D3 foi maior no grupo 5D em relação aos outros grupos e foi maior... / Frequency of hypovitaminosis D in population is high and vitamin D deficiency has been considered a public health problem. Moreover, Vitamin D deficiency is associated with increased risk of many chronic diseases. Thus, it is widespread use of vitamin D without knowing its adverse effects. Studies have shown that this vitamin is important for cardiac development and functioning. Vitamin D deficiency results in cardiac remodeling and vitamin D supplementation in cardiac aggression models attenuates cardiac remodeling. However, influence of vitamin D supplementation in normal rats is not completed known. The aim of this study was to evaluate whether supplementation with vitamin D3 results in cardiac remodeling with changes in structure, function, energy metabolism and inflammatory mediators in the heart of normal rats. We used 86 male rats allocated into four groups: control (C, n = 11) received standard diet; 3D (n = 12), 5D (n = 13) and 10D (n = 11) received 3000, 5000 and 10,000 IU of cholecalciferol / kg diet. After two months the animals were submitted to functional study, morphometric, and biochemical. For the statistical analysis was used the ANOVA test of variance complemented by Tukey, the test Kruskal Wallis complemented by Dunn. To evaluate the dose response was used the Spearman correlation. Serum calcium and phosphorus were higher in the 5D and 10D in relation to the group C. The blood pressure was higher in the groups 3D and 10D in relation to the group C. The increase in blood pressure was dose dependent. Serum 25 (OH) D3 was higher in the group 5D in relation to the other groups and it was higher in the group 10D in relation to the group C. There were no differences in echocardiographic variables of morphology and function. The activity of the enzyme β hydroxyacyl coenzyme A dehydrogenase was smaller in the groups 5D and 10D in relation to other groups... (Complete abstract click electronic access below)