INTRODUÇÃO: Treinamento muscular inspiratório (TMI) tem se mostrado capaz de aumentar a espessura diafragmática. Sabe-se que o diafragma crural age como um esfincter externo do esfíncter inferior do esôfago (EIE), mas é desconhecido se pacientes com hipotonia do EIE se beneficiariam do TMI, a fim de aumentarem a pressão respiratória média (PRM), consequentemente havendo melhora dos sintomas de refluxo gastroesofágico. OBJETIVO: Determinar o resultado dos efeitos do TMI nas pressões respiratória média nos pacientes com doença do refluxo gastroesofágico e seu efeito no tônus do esfíncter inferior do esôfago e compará-los com o grupo controle. MÉTODOS: Vinte pacientes foram incluídos no grupo caso e nove no grupo controle. Todos pacientes tinham a pressão expiratória máxima (PEM) entre cinco e 10mmHg e foram submetidos à manometria esofágica e teste de função pulmonar antes e após oito semanas de treinamento utilizando o threshold IMT (Respironics, Cedar Grove, NJ) duas vezes ao dia. A medida da pressão inspiratória máxima (Pimax) foi aferida a cada duas semanas. O grupo caso teve o threshold IMT ajustado progressivamente, a cada quinze dias, sempre a 30% da nova Pimax. O grupo controle realizou o treinamento com o mesmo aparelho, sob uma pressão constante de 7cmH2O. O nível de significância estatística foi estabelecido a 5% (p £ 0,05). RESULTADOS: A média de idade do grupo caso foi 50,1 ± 18 e no grupo controle de 51,3± 11 anos. Após oito semanas de treinamento utilizando o threshold IMT houve uma melhora na PRM em 15 (75%) pacientes, representando um ganho médio de 46,6% (p<0,01), enquanto no grupo controle, seis (66%) pacientes obtiveram um aumento médio de 26,2% (p<0,01). Não houve diferença estatisticamente significante entre os grupos (p= 0,507). A PEM também aumentou quando comparada com a inicial (p<0,01), mas não diferiu entre os grupos (p= 0,727). Observou-se uma melhora na Pimax no grupo 1 (40% versus 19,6%). Houve um aumento na pressão expiratória máxima (Pemax) em ambos os grupos após as oito semanas de IMT (p< 0,05). CONCLUSÕES: O treinamento muscular inspiratório aumentou as pressões respiratória média e expiratória máxima ao longo das oito semanas em ambos os grupos. Não houve diferença com significância estatística entre os grupos sugerindo que o aumento na pressão do esfíncter inferior do esôfago ocorre independentemente da resistência aplicada ao threshold IMT. Mais estudos são necessários para determinar o impacto clínico desse aumento pressórico e confirmar ou afastar a manutenção dessas pressões a longo prazo / INTRODUCTION: Inspiratory muscle training (IMT) has been shown to increase diaphragm thickness. It is known that the diaphragmatic crural fibers act as an external LES, but it is unknown if patients with hypotensive lower esophageal sphincter (LES) would benefit from IMT increasing the mid-respiratory pressure (MRP), and as such relieving gastroesophageal reflux symptoms. AIM: Evaluate the effect of inspiratory muscle training on MRP in patients with gastroesophageal reflux disease and hypotensive LES and compare it with the control group. PATIENTS AND METHODS: Twenty consecutive patients (progressive loading group) and 9 controls (sham group) were included. All of them had end expiratory pressure (EEP) between 5 and 10mmHg and underwent esophageal manometry and pulmonary function tests before and after 8 weeks of training using a threshold IMT (Respironics, Cedar Grove, NJ) twice daily. The maximal inspiratory pressure (Pimax) measurement was repeated each 2 weeks. The progressive loading group had their threshold IMT set at 30% of their new Pimax. Sham-treated patients (same device but minimal resistance to the air flow) had their threshold set at 7cmH2O and it was maintained constant during the period. The significance level was set at 5% (p £ 0.05). RESULTS: The mean age of progressive loading group was 50.1 ± 11.3 years and sham group was 51.3± 6.3. Following eight weeks of training using a threshold IMT there was an increase in MRP in 15 (75%) patients, representing an average gain of 46.6% (p<0.01), while in the sham group, six (66%) patients had their MRP raised with mean increase of 26.2% (p< 0.01). There was no significant difference between the groups (p= 0.507). EEP also increased when compared with before measured (p<0.01), but did not differ between groups (p= 0.727). It has also been observed an improvement in the Pimax in progressive loading group (40% versus 19.6%). It was observed a gain in the maximal expiratory pressure (Pemax) as well in both groups after the 8-week program of IMT (p< 0.05). CONCLUSION: Inspiratory muscle training increased MRP and EEP in patients of active and sham-treated group after an 8-week program. There was no significant statistical difference between groups suggesting that the increase in pressure at LES occurs regardless to the resistance loading of threshold IMT. Extended follow-up is necessary to document the long-term benefits of such improvements

(1) Were among the antihypertensive drugs with the lowest likelihood of discontinuation implying a potentially superior tolerability profile (2) Had similar odds of short and long term rates of add-on pharmacotherapy implying a similar efficacy with other drug classes (3) Were associated with statistically similar all cause and CVS mortality (4) Had similar odds of presenting with impaired fasting glucose in the short-term. (5) Had higher odds of presenting with hypercholesterolemia in the short-term but the absolute increase in cholesterol was minimal (in the magnitude of 0.14 mmol/1). > (6) Had similar odds of presenting with hyponatremia and hypokalemia in the short-term. / Due to the large sample size these studies are likely to be representative and are new findings among ethnic Chinese patients presenting with uncomplicated hypertension. These results point towards thiazide diuretics as a favorable first-line antihypertensive agent in the management of uncomplicated hypertension in Hong Kong primary practice, in addition to favorable public health considerations including affordability. These studies are in support of guidelines from international authorities recommending thaizide diuretics as the best choice of first-line antihypertensive agent, and suggest that such international guidelines may be generalizable to patients of Chinese race. (Abstract shortened by UMI.) / In these studies we have characterized the major antihypertensive drug classes in terms of their prescription patterns, efficacy, tolerability and association with adverse clinical as well as biochemical outcomes. The completeness of CDARS and e-CMS of the Hospital Authority allows retrieval and comparison of these clinical outcomes of the commonly used antihypertensive agents. The present studies showed that prescription of CCB and BB were high compared with international trends and that of thiazide particularly low and showed a declining trend. Yet when compared with other drug classes, thiazide diuretics: / Wong Chi Sang. / Adviser: Stewart William Mercer. / Source: Dissertation Abstracts International, Volume: 70-09, Section: B, page: . / Thesis submitted in: September, 2008. / Thesis (M.D.)--Chinese University of Hong Kong, 2009. / Includes bibliographical references (leaves 223-260). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / School code: 1307.

After adjusted for the effect of baseline MCE risk and reduction in SBP, the multivariate meta-regression showed baseline SBP was not significantly related to the RD for all the relevant outcomes examined (p>0.22) except MCE (p=0.0226). However, the baseline MCE risk remained significantly related to the RD for all the outcomes (p&lt;0.01) except CHD (p=0.1011). The reduction in SBP remained significantly related to the RD for deaths due to CVD, MCE, CHF and stroke (p&lt;0.01) but not to the RD for all-cause death (p=0.3788) and CHD (p=0.8755). / Conclusions. This study showed that baseline CVD risk and reduction in blood pressure were strongly and consistently related to the absolute effect of treatment and surprisingly the baseline blood pressure was not. The findings lend direct support to the overall risk approach to primary prevention and suggest that contrary to conventional wisdom and current practice, the overall CVD risk rather than blood pressure alone should be used to identify and treat people to prevent major CVD events through anti-hypertensive drugs. These findings suggest that anti-hypertensive drugs should be given to those who have a high future CVD risk rather than high blood pressure alone so as to achieve better cost-effectiveness of anti-hypertensive drugs for primary prevention. / Data extraction and analyses: Two reviewers independently abstracted data on baseline variables, variables that determine methodological quality, and outcomes. The following main outcomes were assessed: all-cause deaths, deaths due to cardiovascular disease, death due to causes other than CVD, major cardiovascular events (MCE), congestive heart failure (CHF), stroke, and coronary heart disease (CHD). / Key words. hypertension, antihypertensive drugs, cardiovascular disease, meta-analysis, systematic review, randomized controlled trial, primary prevention, baseline risk, evidence based medicine / Meta-analysis was used to obtain the overall odds ratio (OR) and risk difference (RD). Forest plots, bubble plots and funnel plots were used to show the results visually or to check biases. Meta-regression was used to identify factors that may independently determine the effect of antihypertensive drugs. The control CVD risk, initial mean blood pressure and reduction in blood pressure were examined. / Method. Identification of studies: The databases searched included ACP Journal Club, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, Cumulative Index to Nursing & Allied Health Literature, Chinese Medical Current Contents to identify relevant studies between 1966 and 2005. We also examined references from relevant trials, reviews and meta-analyses. For trials to be included in this review, they have to have the following characteristics: (1) essential hypertension in patients of any age, sex and race; (2) treatment intervention is antihypertensive drugs; (3) control intervention is a placebo or no treatment; (4) endpoint outcomes are all-cause death and major cardiovascular events; and (5) randomized controlled trials. / Objective. Although the overall risk approach to cardiovascular disease (CVD) primary prevention has been widely adopted, direct evidence that supports this policy is however weak and in some aspects lacking. Importantly, there is no direct evidence to show, between blood pressure and CVD risk, which is a better predictor of the absolute benefit from anti-hypertensive drugs. The evidence that the absolute benefit increases as the future CVD risk increases does not necessarily mean that treating high risk people will be more cost-effective than treating hypertensive people as blood pressure may also be positively related to treatment benefit. The high risk approach would be preferable only when we can show with strong evidence that blood pressure is not related to the absolute benefit of treatment or the CVD risk is much more strongly related to the benefit than blood pressure. We thus conducted this systematic review to examine the evidence from randomized controlled trials to directly show how blood pressure and CVD risk are related to the absolute benefit from anti-hypertensive drugs and compare the capability of the two factors in predicting the benefit. The stronger predictor should be a better indicator for identifying those who should be treated with anti-hypertensive drugs. / Results. Twenty-two eligible randomized controlled trials with a total of 55,448 participants were identified from 1967 to 2004. The average follow-up was 45.6 months ranging from 13 to 84 months. The combined RD and OR for all-cause deaths, deaths due to CVD, MCE, CHF, Stroke and CHD were all statistically significant, showing a consistent and considerable reduction in the risk of these outcomes due to the treatment of anti-hypertensive drugs (p&lt;0.01). / Jiang, Yu. / "September 2007." / Adviser: Jin Ling Tang. / Source: Dissertation Abstracts International, Volume: 69-08, Section: B, page: 4657. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2007. / Includes bibliographical references (p. 107-115). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract in English and Chinese. / School code: 1307.

Fung Yin Lee, Annie. / "January 2004." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2004. / Includes bibliographical references (p. 132-146). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

Ng, Chun Fai. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2010. / Includes bibliographical references (leaves 134-150). / Abstracts in English and Chinese. / Abstract --- p.i / Acknowledgements --- p.vii / Table of Contents --- p.ix / Abbreviations --- p.xii / List of Figures --- p.xv / List of Tables --- p.xviii / Chapter Chapter 1 --- Introduction --- p.1 / Chapter 1.1 --- "Introduction to Cardiovascular Disease, Hypertension and Atherosclerosis" --- p.1 / Chapter 1.1.1 --- Cardiovascular Disease --- p.1 / Chapter 1.1.2 --- Hypertension --- p.2 / Chapter 1.1.2.1 --- Background --- p.2 / Chapter 1.1.2.2 --- Causes of Hypertension --- p.3 / Chapter 1.1.2.3 --- Current Western Management and Medication --- p.6 / Chapter 1.1.3 --- Atherosclerosis --- p.9 / Chapter 1.1.3.1 --- Background --- p.9 / Chapter 1.1.3.2 --- Pathogenesis of Atherosclerosis --- p.10 / Chapter 1.1.3.3 --- Current Western Treatment and Medication --- p.12 / Chapter 1.2 --- Selection and Introduction of Current Chinese Medicine Formula --- p.16 / Chapter 1.2.1 --- Cardiac Syndrome in Traditional Chinese Medicine --- p.16 / Chapter 1.2.2 --- Traditional Chinese Medicine as an Complementary or Alternative Medicine --- p.17 / Chapter 1.2.3 --- Selection of TCM Formula from Pharmacopoeia --- p.18 / Chapter 1.2.3.1 --- Compound Formula --- p.18 / Chapter 1.2.4 --- Introduction to Constitutional Herbal Medicine --- p.19 / Chapter 1.2.4.1 --- Danshen (Radix Salviae miltiorrhizae) --- p.19 / Chapter 1.2.4.2 --- Gegen (Radix Puerariae lobatae) --- p.20 / Chapter 1.2.4.3 --- Yanhusuo (Rhizoma Corydalis) --- p.21 / Chapter 1.2.4.4 --- Composition of the Final Formula Used in the Present Study --- p.21 / Chapter 1.2.5 --- Previous work on Danshen-Gegen Formula and its limitations --- p.22 / Chapter 1.3 --- Objectives of the Present Study --- p.25 / Chapter 1.3.1 --- Research Plan --- p.26 / Chapter Chapter 2 --- Experimental Design and General Methodology --- p.27 / Chapter 2.1 --- Source and Authentication of Raw Herbs --- p.27 / Chapter 2.2 --- Materials --- p.29 / Chapter 2.3 --- Ethical Approval --- p.31 / Chapter 2.4. --- General Methods --- p.32 / Chapter 2.4.1 --- Blood Pressure Measurement --- p.32 / Chapter 2.4.2 --- Blood Profile Measurement --- p.33 / Chapter 2.4.3 --- Vascular Reactivity Studies --- p.36 / Chapter 2.5 --- Statistical Analysis --- p.38 / Chapter Chapter 3 --- Anti-hypertensive Studies of Danshen-Gegen Formula on Rat --- p.39 / Chapter 3.1 --- Introduction --- p.39 / Chapter 3.1.1 --- In vivo Anti-Hypertensive Studies --- p.39 / Chapter 3.1.1.1 --- Spontaneously Hypertensive Rat (SHR) --- p.40 / Chapter 3.1.1.2 --- Tail-cuff Blood Pressure Measurement --- p.41 / Chapter 3.1.2 --- Detailed Underlying Mechanistic Studies --- p.42 / Chapter 3.1.2.1 --- Nitric Oxide-mediated Vasodilation --- p.42 / Chapter 3.1.2.2 --- Prostacyclin-mediated Vasodilation --- p.43 / Chapter 3.1.2.3 --- Hyperpolarization-mediated Vasodilation --- p.43 / Chapter 3.1.2.4 --- Endothelium-dependent/-independent Vasodilation --- p.46 / Chapter 3.1.3 --- Long Term Underlying Mechanistic Studies --- p.48 / Chapter 3.2 --- Methods --- p.49 / Chapter 3.2.1 --- In vivo Anti-Hypertensive Studies --- p.49 / Chapter 3.2.2 --- Detailed Underlying Mechanistic Studies --- p.51 / Chapter 3.2.3 --- Long Term Underlying Mechanistic Studies --- p.53 / Chapter 3.2.4 --- Statistical analysis --- p.56 / Chapter 3.3 --- Results --- p.58 / Chapter 3.3.1 --- In vivo Anti-Hypertensive Studies --- p.58 / Chapter 3.3.1.1 --- Preventive Effect in Hypertension --- p.58 / Chapter 3.3.1.2 --- Therapeutic Effect in Hypertension --- p.62 / Chapter 3.3.2 --- Detailed Underlying Mechanistic Studies --- p.66 / Chapter 3.3.2.1 --- DG extract-induced Vasodilation --- p.66 / Chapter 3.3.2.2 --- Endothelium-independent Vasodilation --- p.67 / Chapter 3.3.2.3 --- Nitric Oxide-mediated Vasodilation --- p.68 / Chapter 3.3.2.4 --- Prostacyclin-mediated Vasodilation --- p.69 / Chapter 3.3.2.5 --- Hyperpolarization-mediated Vasodilation --- p.70 / Chapter 3.3.3 --- Long Term Underlying Mechanistic Studies --- p.74 / Chapter 3.4 --- Discussion --- p.79 / Chapter Chapter 4 --- Anti-atherosclerosis Studies of Danshen-Gegen Formula in Rabbits --- p.89 / Chapter 4.1 --- Introduction --- p.89 / Chapter 4.1.1 --- Intima-Media Thickening --- p.89 / Chapter 4.1.2 --- Effect of High Cholesterol Diet in Rabbit --- p.90 / Chapter 4.1.3 --- Thiobarbituric Acid Reactive Substances --- p.91 / Chapter 4.2 --- Methods --- p.93 / Chapter 4.2.1 --- Pilot Study for Establishment of Experimental Protocol --- p.93 / Chapter 4.2.2 --- Effect of DG extract on Intima-media Thickening --- p.97 / Chapter 4.2.3 --- Statistical analysis --- p.99 / Chapter 4.3 --- Result --- p.100 / Chapter 4.3.1 --- Study of the Anti-atherosclerosis Effect of DG extract - First Run --- p.100 / Chapter 4.3.2 --- Study of the Anti-atherosclerosis Effect of DG extract - Second Run --- p.108 / Chapter 4.4 --- Discussion --- p.117 / Chapter Chapter 5 --- General Discussion and Conclusion --- p.122 / Chapter 5.1 --- Significance of the Study --- p.122 / Chapter 5.2 --- Limitations and Future work --- p.127 / Chapter 5.3 --- Clinical Implication of the Use of the DG Preparations for Patients with CVD --- p.132 / References --- p.134

Abstract not available

Made available in DSpace on 2015-05-14T12:59:52Z (GMT). No. of bitstreams: 1 arquivototal.pdf: 3215575 bytes, checksum: 8de9cf3f200ed4dc0ee4d1b0b672ce4f (MD5) Previous issue date: 2012-08-29 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / The number of alkaloids containing the 1-substituted tetrahydroisoquinoline skeleton is extensive and impressive versatility of this pharmacological class arouses interest in experimental pharmacologists. Applying the consecrated Pictet-Spengler reaction of four phenyltetrahydroisoquinoline alkaloids was obtained, three of which are unpublished. Two of them obtained with excellent yield (93.45%) in one step. Starting from allylbenzene that initially passed through an isomerization followed by oxidation by applying the Limieux-Johnson reaction were obtained from two other alkaloids with an overall yield of 50%. In experimental models of acute inflammation, the 1-(3-methoxy-4-hydroxyphenyl)-7-methoxy-1,2,3,4,tetrahydroisoquinoline (MTHP) significantly reduced (p <0.05) cell migration into the abdominal cavity of mice and the release of pro-inflammatory mediators (TNF-α, IL-1 and IL-6) in a dose one hundred thirty-eight times lower dosage than the dose of aspirin administered (200 mg/Kg).The MTHP causes hypotension in non-anesthetized normotensive rats, which can be attributed to the participation of endothelium-derived factors, including NO and metabolites COX. These data suggest that MTHP has anti-inflammatory and hypotensive effect related to different mechanisms, and further studies are needed to explore its potential. / O número de alcaloides que contém o esqueleto tetrahidroisoquinolínico 1-substituído é extenso e a impressionante versatilidade farmacológica desta classe desperta o interesse nos farmacologistas experimentais. Aplicando a consagrada reação de Pictet-Spengler obtivemos quatro alcaloides fenil tetrahidroisoquinolínicos dos quais três são inéditos. Dois deles obtidos com excelente rendimento (93,45%) em uma única etapa. Partindo-se de alilbenzenos que inicialmente passaram por uma isomerização seguida de oxidação via reação de Limieux-Johnson, foram obtidos os outros dois alcaloides com rendimento global de 50%. Em modelo experimental de inflamação aguda, a 1-(3-metoxi-4-hidroxifenil)-7-metoxi-1,2,3,4,-tetrahidroisoquinolina (MTHP) reduziu significativamente (p<0,05) a migração celular para a cavidade abdominal de camundongos bem como a liberação dos mediadores pró-inflamatórios (TNF-, IL-1 e IL-6) em uma dose cento e trinta e oito vezes menor que a dose de AAS administrada (200mg/Kg i.p.). MTHP provoca hipotensão em ratos normotensos não anestesiados, que pode ser atribuída à participação de derivados do endotélio, incluindo fatores de NO e metabolitos COX. Estes dados sugerem que MTHP tem efeitos anti-inflamatórios e hipotensores relacionados a diferentes mecanismos, e novos estudos são necessários para explorar seu potencial.

INTRODUÇÃO: Treinamento muscular inspiratório (TMI) tem se mostrado capaz de aumentar a espessura diafragmática. Sabe-se que o diafragma crural age como um esfincter externo do esfíncter inferior do esôfago (EIE), mas é desconhecido se pacientes com hipotonia do EIE se beneficiariam do TMI, a fim de aumentarem a pressão respiratória média (PRM), consequentemente havendo melhora dos sintomas de refluxo gastroesofágico. OBJETIVO: Determinar o resultado dos efeitos do TMI nas pressões respiratória média nos pacientes com doença do refluxo gastroesofágico e seu efeito no tônus do esfíncter inferior do esôfago e compará-los com o grupo controle. MÉTODOS: Vinte pacientes foram incluídos no grupo caso e nove no grupo controle. Todos pacientes tinham a pressão expiratória máxima (PEM) entre cinco e 10mmHg e foram submetidos à manometria esofágica e teste de função pulmonar antes e após oito semanas de treinamento utilizando o threshold IMT (Respironics, Cedar Grove, NJ) duas vezes ao dia. A medida da pressão inspiratória máxima (Pimax) foi aferida a cada duas semanas. O grupo caso teve o threshold IMT ajustado progressivamente, a cada quinze dias, sempre a 30% da nova Pimax. O grupo controle realizou o treinamento com o mesmo aparelho, sob uma pressão constante de 7cmH2O. O nível de significância estatística foi estabelecido a 5% (p £ 0,05). RESULTADOS: A média de idade do grupo caso foi 50,1 ± 18 e no grupo controle de 51,3± 11 anos. Após oito semanas de treinamento utilizando o threshold IMT houve uma melhora na PRM em 15 (75%) pacientes, representando um ganho médio de 46,6% (p<0,01), enquanto no grupo controle, seis (66%) pacientes obtiveram um aumento médio de 26,2% (p<0,01). Não houve diferença estatisticamente significante entre os grupos (p= 0,507). A PEM também aumentou quando comparada com a inicial (p<0,01), mas não diferiu entre os grupos (p= 0,727). Observou-se uma melhora na Pimax no grupo 1 (40% versus 19,6%). Houve um aumento na pressão expiratória máxima (Pemax) em ambos os grupos após as oito semanas de IMT (p< 0,05). CONCLUSÕES: O treinamento muscular inspiratório aumentou as pressões respiratória média e expiratória máxima ao longo das oito semanas em ambos os grupos. Não houve diferença com significância estatística entre os grupos sugerindo que o aumento na pressão do esfíncter inferior do esôfago ocorre independentemente da resistência aplicada ao threshold IMT. Mais estudos são necessários para determinar o impacto clínico desse aumento pressórico e confirmar ou afastar a manutenção dessas pressões a longo prazo / INTRODUCTION: Inspiratory muscle training (IMT) has been shown to increase diaphragm thickness. It is known that the diaphragmatic crural fibers act as an external LES, but it is unknown if patients with hypotensive lower esophageal sphincter (LES) would benefit from IMT increasing the mid-respiratory pressure (MRP), and as such relieving gastroesophageal reflux symptoms. AIM: Evaluate the effect of inspiratory muscle training on MRP in patients with gastroesophageal reflux disease and hypotensive LES and compare it with the control group. PATIENTS AND METHODS: Twenty consecutive patients (progressive loading group) and 9 controls (sham group) were included. All of them had end expiratory pressure (EEP) between 5 and 10mmHg and underwent esophageal manometry and pulmonary function tests before and after 8 weeks of training using a threshold IMT (Respironics, Cedar Grove, NJ) twice daily. The maximal inspiratory pressure (Pimax) measurement was repeated each 2 weeks. The progressive loading group had their threshold IMT set at 30% of their new Pimax. Sham-treated patients (same device but minimal resistance to the air flow) had their threshold set at 7cmH2O and it was maintained constant during the period. The significance level was set at 5% (p £ 0.05). RESULTS: The mean age of progressive loading group was 50.1 ± 11.3 years and sham group was 51.3± 6.3. Following eight weeks of training using a threshold IMT there was an increase in MRP in 15 (75%) patients, representing an average gain of 46.6% (p<0.01), while in the sham group, six (66%) patients had their MRP raised with mean increase of 26.2% (p< 0.01). There was no significant difference between the groups (p= 0.507). EEP also increased when compared with before measured (p<0.01), but did not differ between groups (p= 0.727). It has also been observed an improvement in the Pimax in progressive loading group (40% versus 19.6%). It was observed a gain in the maximal expiratory pressure (Pemax) as well in both groups after the 8-week program of IMT (p< 0.05). CONCLUSION: Inspiratory muscle training increased MRP and EEP in patients of active and sham-treated group after an 8-week program. There was no significant statistical difference between groups suggesting that the increase in pressure at LES occurs regardless to the resistance loading of threshold IMT. Extended follow-up is necessary to document the long-term benefits of such improvements

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.

Pulmonary circulation is a high flow, low resistance, and low pressure system. Several pathologies, including mitral stenosis, may elevate the impedance of this blood circuit and lead to a pulmonary arterial hypertension. Such syndrome is usually related to a high morbity and patient s death may occur because of the ischemic failure of right ventricle. The use of systemic vasodilating drugs to treat this syndrome is limited by the simultaneous systemic arterial hypotension they often produce. More selective agents to the pulmonary vasculature, such as synthetic analogs of prostacyclin, endothelin receptor inhibitors, and phosphodiesterase III inhibitors, have been choosen for medium and long-term treatment. Unfortunately, the most selective pulmonary hypotensive agent, the inhaled nitric oxide, which is used for short-term treatment, requires special and costly equipment for its administration, making it inaccessible to many hospitals. Furthermore, some degree of toxicity was associated with that substance. The lack of an ideal substance that simultaneously shows pulmonary selectivity, atoxicity, easy handling, accessibility and low cost, motivated the present study to test the effects of clonidine on pulmonary circulation. Clonidine is an alfa-2 adrenergic agonist. It promotes a systemic cardiocirculatory balance by modulating the adrenergic discharge at both central and peripheral levels. When used in clinical doses it presents no toxicity. Furthermore, it is easy to handle, accessible, and inexpensive. However, little has been reported about its pulmonary effect. Therefore, this work aimed to evaluate the effects of clonidine on the pulmonary arterial pressure, on the hemodynamics parameters concerned to the pulmonary circulatory system, as well as on the right ventricular function. At the same time, the action of clonidine on the systemic hemodynamics, cardiac rate, cardiac index and stroke index was also evaluated. This investigation took into account the degree of selectivity of this agent to the pulmonary vessels as well as the presence of a biphasic effect on the pulmonary arterial pressure. This effect has been largely reported on the vascular periferal system. The present research was performed as a prospective clinical trial developed on a group of 16 patients with pulmonary hypertension caused by mitral stenosis of rheumatic origin. Data were obtained before the anesthetic induction, but under the patient sedation. During the control phase, the variations of hemodynamic parameters under the action of a placebo were evaluated. During the test phase, the behavior of these parameters was evaluated under the clonidine effect. The time schedule for data measurements was the following: T0 (initial control); T1 (10 minutes after placebo administration); T2 (20 minutes after placebo administration); T3 (10 minutes after clonidine administration); T4 (20 minutes after clonidine administration). T2 was used as the control time to study the clonidine effects. Statistical analysis showed that during the control phase the variables remained unchanged, but under the effect of clonidine there was a significant reduction of the mean values concerned to the following parameters: pulmonary arterial mean pressure (27.1%) and systemic arterial mean pressure (20%), pulmonary vascular resistance index (34%) and systemic vascular resistance index (14.6%), right and left ventricular systolic work indexes (19.9% and 10%, respectively), right atrium pressure (11.5%), pulmonary arterial wedge pressure (21.5%), heart rate and cardiac index (15.8% and 7.9%, respectively). Besides that, a significant increase of the stroke index (10.2%) occured. The biphasic effect on the sistemic arterial pressure occured in 50% of the studied patients, whereas the same effect on the pulmonary arterial pressure was observed in 20% of the same sample. Clonidine also exerted a moderately selective action on the pulmonary circulation, demonstrated through the reduction of the relationship between mean value of the pulmonary vascular resistance index and mean value of the systemic vascular resistance index evaluated at the times T2 and T3. / A circulação pulmonar é um sistema de alto fluxo, baixa resistência e baixa pressão. Patologias diversas, dentre elas a estenose mitral, podem elevar a impedância desse circuito, desencadeando a síndrome de hipertensão arterial pulmonar. Esta cursa com elevada morbidade, podendo levar ao óbito pela falência isquêmica do ventrículo direito. A utilização de drogas vasodilatadoras periféricas no tratamento dessa síndrome ficou limitada pela simultânea hipotensão arterial sistêmica que provoca. Agentes mais seletivos sobre a vasculatura pulmonar, como os análogos sintéticos da prostaciclina, os inibidores dos receptores de endotelina e os inibidores da fosfodiesterase III, têm sido as drogas de eleição para o tratamento de médio e de longo prazo. O mais seletivo dos agentes hipotensores pulmonares, o óxido nítrico inalado, aplicado ao tratamento de curto prazo, exige equipamento especial e oneroso para a sua administração, tornando-o inacessível a muitos nosocômios. Paralelamente, possui potencial toxicidade. A inexistência de um fármaco ideal que apresente, simultaneamente, seletividade sobre a pequena circulação, atoxicidade, fácil manuseio e disponibilidade, além de ser pouco oneroso, conduziu ao estudo da clonidina sobre a árvore circulatória pulmonar. Este agente terapêutico é um agonista alfa-2 adrenérgico, com efeitos favoráveis reconhecidos sobre o equilíbrio circulatório sistêmico por modular a descarga adrenérgica em níveis central e periférico. É atóxico quando utilizado em doses clínicas. Além disso, oferece fácil manuseio, boa acessibilidade e baixo custo. Os estudos a respeito da sua ação pulmonar são escassos. Assim, a presente investigação teve como objetivo avaliar os efeitos da clonidina sobre a pressão arterial pulmonar, sobre os demais parâmetros hemodinâmicos da pequena circulação e sobre a função ventricular direita. Paralelamente, analisou as ações sobre a hemodinâmica sistêmica, a freqüência cardíaca, o índice cardíaco e o índice de ejeção. Foi também investigado o grau de seletividade pulmonar desse agente, bem como a presença de um efeito bifásico sobre a pressão arterial pulmonar, pois este efeito tem sido amplamente relatado no sistema vascular periférico. Para a execução dos objetivos propostos, um ensaio clínico prospectivo, realizado antes da indução anestésica, mas sob sedação, foi desenvolvido num grupo de 16 pacientes, todos portadores de hipertensão pulmonar resultante de estenose mitral de origem reumática. Durante a fase controle foram analisadas as variações dos parâmetros hemodinâmicos sob a ação de um placebo. Durante a fase teste foi avaliado o comportamento dos mesmos parâmetros sob a ação da clonidina. A padronização dos tempos nos quais se fez a coleta de dados foi a seguinte: T0 (controle inicial); T1 (10 min após a administração do placebo); T2 (20 min após o placebo); T3 (10 min após a administração da clonidina); T4 (20 min após a clonidina). A análise estatística dos resultados demonstrou não haver alteração das variáveis estudadas durante a fase controle. Todavia, sob o efeito da clonidina houve variações estatisticamente significantes dos mesmos parâmetros nos seus valores médios: redução da pressão arterial pulmonar média (27,1%) e da pressão arterial sistêmica média (20%), dos índices de resistência vascular pulmonar (34%) e sistêmica (14,6%), dos índices de trabalho sistólico dos ventrículos direito (19,9%) e esquerdo (10%), da pressão do átrio direito (11,5%), da pressão de oclusão da artéria pulmonar (21,5%), da freqüência cardíaca (15,8%) e do índice cardíaco (7,9%), ao lado de uma elevação significante do índice de ejeção (10,2%). O efeito bifásico sobre a pressão arterial sistêmica ficou evidente em 50% dos pacientes estudados, enquanto que o mesmo efeito sobre a pressão arterial pulmonar ocorreu em 20% da amostra estudada. A clonidina também exerceu uma ação moderadamente seletiva sobre a circulação pulmonar, demonstrada através da diminuição do quociente obtido entre o valor médio do índice de resistência vascular pulmonar e valor médio do índice de resistência vascular sistêmica, ambos avaliados nos tempos T2 e T3.