Made available in DSpace on 2016-06-02T20:19:26Z (GMT). No. of bitstreams: 1 6645.pdf: 2027088 bytes, checksum: 18fe5648e0835cf1cfcbef303f079520 (MD5) Previous issue date: 2015-02-27 / Universidade Federal de Sao Carlos / In chronic obstructive pulmonary disease (COPD), functional and structural impairment of lung function can negatively impact heart rate variability (HRV); in addition, a reduced exercise capacity is an important independent prognostic marker in COPD patients. However, 1) if the degree of lung impairment negatively impacts HRV responses and 2) whether the injury of the autonomic control may be associated with reduced exercise capacity in patients with COPD remain unclear. Thus, two studies were conducted in order to verify if functional status at rest and during exercise would be related to autonomic impairment in COPD patients. In the first study, entitled "Relationship between linear and nonlinear dynamics of heart rate and impairment of lung function in COPD patients," we investigated whether the impairment static lung volumes and lung diffusion capacity (DL) would be related to HRV indices in moderate-to-severe COPD. Sixteen patients with COPD underwent pulmonary function tests (spirometry, plethysmography and lung diffusion capacity for carbon monoxide - DLCO). The RR interval was registered in the supine, standing and seated positions and during a respiratory sinus arrhythmia maneuver (M-RSA). Our results suggest that responses of HRV indices were more prominent during M-RSA in moderate-to-severe COPD. Moreover, greater lung function impairment was related to poorer heart rate dynamics. Finally, impaired DLCO is related to an altered parasympathetic response in these patients. The second study, entitled "Are linear and nonlinear heart rate dynamics in submaximal exercise related to cardiorespiratory responses during maximal exercise in patients with COPD?", we inquired whether there is a relationship between HRV responses and exercise capacity in patients with COPD. Fifteen patients underwent incremental cardiopulmonary exercise testing and six-minute walk test (6MWT). The RR interval was registered at rest (standing position) and during 6MWT. Our results showed that HRV responses at rest and during simple field tests may reflect functional impairment of COPD patients, providing important information about both ventilatory and hemodynamic inefficiency in these patients. / Em pacientes com doença pulmonar obstrutiva crônica (DPOC), as alterações funcionais e estruturais do pulmão podem impactar negativamente na variabilidade da frequência cardíaca (VFC). Além disso, a reduzida capacidade de exercício se traduz como um marcador prognóstico nesses pacientes. No entanto, ainda não estão esclarecidos 1) se o grau de comprometimento pulmonar tem impacto negativo sobre as respostas da VFC, frente a diferentes estímulos autonômicos, e 2) se o prejuízo no controle autonômico pode estar relacionado à reduzida capacidade de exercício nos pacientes com DPOC. Sendo assim, dois estudos foram realizados com o intuito de relacionar as alterações funcionais, no repouso e no exercício, com o grau de prejuízo autonômico em pacientes com DPOC. O primeiro estudo, cujo título é Correlação entre as dinâmicas linear e não linear da frequência cardíaca e o comprometimento da função pulmonar em pacientes com DPOC , teve como objetivo investigar se o comprometimento nos volumes pulmonares estáticos e na difusão pulmonar estaria relacionado aos índices da VFC em repouso e em resposta às mudanças posturais. Dezesseis pacientes com diagnóstico de DPOC foram submetidos à prova de função pulmonar (espirometria, pletismografia e capacidade de difusão pulmonar ao monóxido de carbono DCO) e à coleta da VFC nas posturas supino, ortostatismo e sentado e durante a manobra de arritmia sinusal respiratória (M-ASR). Nossos resultados sugerem que as respostas da VFC frente a um estímulo vagal (M-ASR) são mais evidentes. Ainda, quanto maior o comprometimento da função pulmonar pior a dinâmica da frequência cardíaca. Por fim, a redução da DCO está relacionada à alterada resposta vagal nos pacientes com DPOC. O segundo estudo, intitulado Os índices da dinâmica linear e não linear na frequência cardíaca no exercício submáximo estão relacionados com as respostas cardiorrespiratórias ao exercício máximo em pacientes com DPOC? teve por objetivo avaliar se existe relação entre as respostas da VFC e a capacidade de exercício em pacientes com DPOC. Quinze pacientes foram submetidos aos testes de exercício cardiopulmonar incremental e de caminhada de seis minutos (TC6). A coleta da VFC feita em repouso (ortostatismo) e durante o TC6. Os resultados mostraram que as respostas da VFC no repouso e em testes simples de campo podem inferir o prejuízo funcional de pacientes com DPOC, fornecendo informações importantes acerca das limitações ventilatória e hemodinâmica destes pacientes.

Ce travail a été consacré à l’étude non invasive de la circulation pulmonaire normale par mise en œuvre de l’échocardiographie Doppler. <p>En intégrant les mesures obtenues dans une approche physiopathologique, et en exploitant les nouvelles possibilités d’échocardiographes portables, techniquement performants, nous avons analysé les effets d’un inhibiteur de la phosphodiestérase-5 et d’une prostacycline, pour tenter d’en identifier d’éventuels effets introtropes intrinsèques, nous avons exploré le concept de réserve vasculaire pulmonaire comme facteur limitant de l’aptitude aérobie et indice potentiel d’une atteinte vasculaire pulmonaire précoce, et obtenu des résultats préliminaires permettant d’identifier une hypertension artérielle pulmonaire (HTAP) latente. Nos principaux résultats peuvent être résumés comme suit :<p>1. Chez le sujet sain, en normoxie ou dans un modèle expérimental d’HTAP induite par l’inhalation d’un mélange gazeux hypoxique, le sildenafil per os ou l’epoprostenol par voie intraveineuse, à des doses utilisées en clinique pour le traitement de l’HTAP, améliorent les indices de la fonction ventriculaire droite en proportion de leurs effets vasodilatatoires pulmonaires, sans effets inotropes intrinsèques détectables.<p>2. La consommation d’oxygène maximale du sujet sain augmente en raison directe de son volume capillaire pulmonaire (calculé à partir de sa capacité de diffusion pour l’oxyde nitrique et le monoxyde de carbone) et en raison inverse de sa résistance vasculaire pulmonaire, non seulement en altitude, mais aussi au niveau de la mer. Ce résultat suggère qu’une plus grande réserve vasculaire pulmonaire est propice aux efforts aérobiques intenses, probablement par moindre postcharge ventriculaire droite.<p>3. Des mesures réalisées chez un petit nombre de sujets suggèrent que la distensibilité vasculaire pulmonaire, calculée à partir d’une relation débit-pression vasculaire pulmonaire, est typiquement réduite chez des porteurs asymptomatiques de la mutation BMPR2, qui est actuellement le facteur de risque le plus élevé connu de l’HTAP. La mutation BMPR2 pourrait aussi être associée à une réactivité vasculaire pulmonaire accrue à l’hypoxie. <p>Nos résultats suggèrent indirectement que l’échocardiographie Doppler, de repos ou de stress, pourrait être davantage développée dans la mise au point de patients à risque d’HTAP./<p><p>Novel advances in echocardiography offer the opportunity to reliably characterize pulmonary circulation in terms of pressure-flow relationship, and to better understand the coupling of right ventricular (RV) function with normal and abnormal pulmonary hemodynamics. Moreover, when combined with the measurement of pulmonary capillary blood volume, this renewed methodological approach may help to understand the concept of pulmonary vascular reserve as a limiting factor of exercise capacity and potential sensitive marker of early vascular disease.<p><p>In the present work we used a model of hypoxic pulmonary vasoconstriction to analyse the effects of two targeted therapies of pulmonary arterial hypertension (PAH) on the RV function. We showed that the beneficial effects of these drugs are mainly driven by a decrease in RV afterload and not an enhanced myocardial inotropic state. Whether this is transposable to abnormal RV-arterial coupling in PAH patients remains to be investigated.<p><p>Echocardiography may be useful to explore the pulmonary vascular reserve as an important limiting factor of exercise capacity. We showed that a higher pulmonary vascular reserve, defined by a decreased PVR and increased lung diffusing capacity, allows for an improved aerobic exercise capacity (as assessed by a higher peak oxygen consumption), at a lower ventilatory cost, at sea level and at high altitude. <p><p>Stress echocardiography may detect an abnormal pulmonary vasoreactivity. We showed that asymptomatic relatives of patients suffering from idiopathic pulmonary arterial hypertension, and who carry a bone morphogenetic protein receptor type 2 mutation (BMPR2) present with a decreased pulmonary vascular distensibility and an enhanced pulmonary vasoreactivity to hypoxia, which are identifiable by echocardiography examination. However, the predictive value of these findings is not known. <p><p>Thus echocardiography may represent, in experienced and dedicated hands, a noninvasive, safe, widely available, applicable at the bed-side as well as in extreme environment (e.g. high altitudes), less expensive alternative for the evaluation of the pulmonary circulation, either by the interrogation of pressure-flow relationship (stress echocardiography), by the investigation of the right ventricle global and regional function in relation to its afterload (standard and Tissue Doppler Imaging), or by a combined approach with the measurement of lung diffusing capacity (DLNO / DLCO) to assess the pulmonary vascular reserve.<p><p>The present data are encouraging for further development and implementation of echocardiography for the detection, but also the diagnosis and follow-up of patients with pulmonary hypertension.<p><p> / Doctorat en Sciences médicales / info:eu-repo/semantics/nonPublished