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京都大学 / 新制・課程博士 / 博士(工学) / 甲第23860号 / 工博第4947号 / 新制||工||1773(附属図書館) / 京都大学大学院工学研究科都市社会工学専攻 / (主査)教授 岸田 潔, 教授 三村 衛, 教授 木村 亮 / 学位規則第4条第1項該当 / Doctor of Philosophy (Engineering) / Kyoto University / DGAM

<p><strong>Purpose: </strong>Habitual aerobic exercise improves vascular function; however, the acute vascular response to exercise is poorly understood. The present investigation compared the time course of acute changes in vascular function following two different types of aerobic exercise. <strong>Methods: </strong>Ten untrained males (23 ± 2 yrs) completed one bout of sustained moderate-intensity cycling (END) (30 mins at 55% peak power) or high-intensity interval (HIT) cycling (10 one-minute intervals at 80% peak power) on different days. Endothelium-dependent dilation was assessed by brachial artery flow-mediated dilation (baFMD) at baseline, immediately post-exercise, 1 hour post-exercise and 24 hours post-exercise. Endothelium-independent dilation was assessed via nitroglycerin (NTG) at all time points, except 1 hour post-exercise. <strong>Results:</strong> baFMD values were not significantly different between END and HIT at any time point. Immediately post-exercise baFMD values were unchanged from baseline. 1 Hour post-exercise, relative (p £ 0.001) and absolute (p £ 0.05) baFMD values were attenuated compared to all other time points for both HIT (%FMD baseline: 5.9 ± 2.3%; 1 hour post-exercise: 2.5 ± 1.5%) and END (%FMD baseline: 6.8 ± 2.4%; 1 hour post-exercise: 2.6 ± 1.9%). Relative (p £ 0.05) and absolute (p £ 0.05) NTG responses were attenuated immediately post-exercise compared to baseline for both HIT (%NTG baseline: 18.8 ± 4.4%; immediately post-exercise: 12.3 ± 3.1%) and END (%NTG baseline: 18.3 ± 3.1%; immediately post-exercise: 10.9 ± 4.9%). <strong>Conclusions: </strong>Immediately post-exercise, endothelium-dependent dilation is maintained; but reduced 1 hour following exercise cessation. Similar acute vascular responses are found following HIT and END.</p> / Master of Science in Kinesiology

Endothelial function is influenced by a variety of factors, including shear stress direction and magnitude. Whereas improvements in endothelial function have mostly been attributed to increased anterograde flow, the results of many interventional models in humans suggest that enhancing blood flow in both anterograde and retrograde directions to create a high shear stress oscillatory stimulus may be optimal for improving endothelial function. Well-controlled studies are necessary to further this theory. The purposes of this study were to determine the brachial artery acute shear stress and endothelial function responses to (1) passive heat stress (HEAT), (2) ECG-gated cuff compressions (CUFF), and (3) ECG-gated rhythmic handgrip exercise (HGEX); and (4) to determine if there is a relationship between the degree of shear stress oscillation and endothelial function, regardless of the stimulus applied. We hypothesized that (1) HEAT would increase anterograde shear stress and decrease retrograde shear stress, leading to an unpredictable change in endothelial function; (2) CUFF would increase both anterograde and retrograde shear stress, leading to an increase in endothelial function; (3) HGEX would increase anterograde and retrograde shear stress and exercise metabolites, leading to an increase in endothelial function; and (4) the change in oscillatory shear index would be positively associated with the change in flow-mediated dilation, such that an increment increase in the degree of shear stress oscillation would be accompanied by a proportional improvement in endothelial function. In separate visits, 10 young healthy males (22±3 years) underwent 10 minutes of unilateral HEAT, CUFF, or HGEX on the left arm (EXP), while the right arm served as a within-subject time control (CON). Non-invasive finger plethysmography was used to measure heart rate (HR) and blood pressure (BP) throughout the testing sessions. Ultrasonography was used to obtain measures of blood velocity and arterial diameter from the brachial artery of both limbs throughout the interventions. Anterograde and retrograde shear stress (SS) and oscillatory shear index (OSI) were calculated at baseline and during each intervention to assess the blood flow pattern changes. Endothelial function was assessed before and after each intervention, in both limbs simultaneously using a flow-mediated dilation (FMD) test. HEAT increased HR during the intervention (P < 0.05), mean BP and diastolic BP after the intervention (P < 0.05), anterograde SS in EXP (rest: 15.2 ± 2.9 vs. HEAT: 29.8 ± 8.5 dynes/cm2, P < 0.05), and FMD% in both limbs (P = 0.000). CUFF did not change HR or BP, increased anterograde (rest: 17.9 ± 4.1 vs. CUFF: 43.0 ± 12.4 dynes/cm2, P < 0.05) and retrograde (rest: -3.1 ± 2.5 vs. CUFF: -22.7 ± 6.0 dynes/cm2, P < 0.05) SS in EXP, but did not change FMD% in either limb (P = 0.248). HGEX increased HR during the intervention (P < 0.05), mean BP during and after the intervention (P < 0.05), anterograde SS in EXP (rest: 18.7 ± 5.9 vs. HGEX: 56.4 ± 11.5 dynes/cm2, P < 0.05), and FMD% in both limbs (P = 0.001). These findings suggest that an anterograde-dominant shear stress stimulus may be effective at improving endothelial function, but the confounding effect of sympathetic nervous system activation may play a more dominant role in the acute control response for shorter duration interventions such as the ones explored in this study. / Thesis / Master of Science (MSc) / It has been well established that the pattern of blood flow can impact arterial function, but the nuances of this relationship remain unclear. Through the use of heating, cuff compression, and exercise, this study sought to determine the optimal shear stress pattern to see beneficial changes in arterial function in the arm of young healthy males. Our results show many real life interventions alter not only the shear stress pattern in the artery, but also involve other systems like the brain and muscle that are crucial to maintaining the body’s physiological balance. It is clear that arterial function is regulated through a variety of different mechanisms, and that the changes we observe will depend on the parameters (e.g. duration, intensity, timing of assessment) of the applied stimulus. More specifically, isolating study designs should be constructed to determine the individual contributions of different human body systems to the arterial regulatory response.

Endothelium-dependent vasodilation is an important marker of vascular function. Brachial artery flow-mediated dilation (FMD) is a noninvasive assessment of peripheral artery endothelial function that is associated with coronary artery endothelial function and is an index of cardiovascular health. This thesis sought to investigate factors that may influence the brachial artery FMD response in humans, particularly the sex hormone estrogen and low-volume sprint interval training (SIT). We first demonstrated the intra-individual consistency of the FMD response pattern in healthy young adults and introduced visual data screening as a tool for improving data accuracy. Having established best practices for FMD data analysis, we investigated the brachial artery FMD response in adults with different estrogen profiles: men, premenopausal women with a natural menstrual cycle (NAT), and premenopausal women using combined oral contraceptive pills (OCP). Our findings suggest that estrogen does not augment FMD during high-estrogen phases of a NAT or OCP cycle compared to low-estrogen phases or to men. We also investigated the acute and chronic brachial artery FMD response to a 3x20-s low-volume SIT model. Following a single SIT session, FMD was unchanged in men or women. These findings demonstrate that estrogen does not influence endothelium-dependent dilation at rest or following intense intermittent exercise, but also suggest that low-volume SIT may be an insufficient stimulus for eliciting changes in endothelial function. This stimulus magnitude postulation was further supported by a 12-wk exercise training study, whereby vascular changes were evident following moderate-intensity continuous training but not SIT. Taken together, this work suggests that controlling for menstrual cycle phase and/or OCP use in premenopausal women may not be necessary, making it more feasible to include women as research participants, and highlights the need for future characterization of the minimum low-volume interval stimulus that evokes improvements in endothelial function in healthy young adults. / Thesis / Doctor of Philosophy (PhD) / The endothelium is the inner lining of an artery that separates it from the flowing blood. A healthy endothelium responds to increases in blood flow by producing substances that enable an artery to widen. The projects in this thesis examined whether the responsiveness, and overall function, of the endothelium in healthy young adults is enhanced by the sex hormone estrogen or by “all-out” cycling sprints, an exercise protocol that has gained appeal for its time-efficiency. We demonstrated that estrogen does not enhance endothelial function in women, compared to men, at any phase of a menstrual or birth control pill cycle. A single session or 12-weeks of the intense but brief interval exercise also does not enhance endothelial function. This work suggests it may be easier to include women in future research assessing this measure and that this particular interval exercise protocol may not enhance endothelial function in healthy adults.

The thesis investigated the effect of exercise on endothelial function (measured as flow-mediated dilation (FMD)) and triacylglycerol concentrations following the ingestion of a high-fat breakfast and lunch in adolescent boys. The validity of measuring lipid and lipoprotein concentrations from a capillary blood sample, and the reproducibility of the postprandial FMD and triacylglycerol concentration responses to the high-fat meals, was established. The effects of prior continuous moderate-intensity exercise (60 min walking at 60% V̇O₂peak), repeated very short duration sprints (40 x 6 s maximal effort cycle sprints) and accumulated moderate-intensity exercise (6 x 10 min running at 70% V̇O₂peak) on endothelial function and triacylglycerol concentrations in adolescent boys were then established across three studies, each consisting of two, 2-day main trials (control and exercise). On day 1, participants were either inactive or completed the prescribed exercise. On day 2, FMD and triacylglycerol concentrations were measured prior to, and following, ingestion of a high-fat breakfast and lunch. In each control trial FMD was reduced (signifying endothelial dysfunction), compared to fasting, by 20-32% and 24-33% following the high-fat breakfast and lunch. Following continuous moderate-intensity exercise, repeated very-short duration sprints and accumulated moderate-intensity exercise these reductions were only 8% and 10% (main effect trial, P = 0.002; main effect time, P = 0.023; interaction effect trial x time, P = 0.088), 2% and 5% (main effect trial, P = 0.012; main effect time, P = 0.004; interaction effect trial x time, P = 0.003) and 1% and 3% (main effect trial, P = 0.020; main effect time, P < 0.001; interaction effect trial x time, P = 0.014) respectively. The continuous moderate-intensity exercise and repeated very short duration sprints also significantly reduced the total area under the triacylglycerol concentration versus time curve by 22% (Control vs. Exercise; 12.68 (sem 1.37) vs. 9.84 (sem 0.75) mmol L-1 6.5h, P = 0.018) and 13% (Exercise vs. Control: 8.65 (sem 0.97) vs. 9.92 (sem 1.16) mmol L-1 6.5h, P = 0.023). The accumulated moderate-intensity exercise also reduced the total area under the triacylglycerol concentration versus time curve by 11%, but this reduction was not significant (Control vs. Exercise: 10.71 (sem 0.94) vs. 9.56 (sem 0.67) mmol L-1 6.5h, respectively, P = 0.183). The experimental evidence from these studies emphasise that exercise might offer an acceptable, non-pharmacological means of influencing CHD risk when individuals are young. The results of these studies can help shape future physical activity guidelines.

O artigo 5º, inciso LXXVIII, da Constituição da República Federativa do Brasil garante a todos, no âmbito judicial e administrativo, a razoável duração do processo. Trata-se de garantia de conteúdo vago e plurívoco, cuja eficácia depende de disciplina infraconstitucional que especifique o seu conteúdo e alcance. Pelo princípio da reserva legal, e em decorrência do princípio da separação dos poderes, cabe ao Poder Legislativo a delimitação temporal do poder de punir do Estado, restringindo o tempo de duração da coação proveniente da tramitação do processo. Apenas na ausência de prazos legais máximos de duração do processo é que se admite a atividade interpretativa integrativa por parte do Poder Judiciário, de molde a garantir a aplicabilidade imediata da norma, que versa sobre direito fundamental. Em auxílio a esta difícil tarefa hermenêutica, de estabelecer um marco a partir do qual não se justifica mais a continuidade do processo, porque ultrapassado o prazo razoável de sua duração, alguns critérios consagrados internacionalmente podem ser utilizados, como é o caso da complexidade da causa, comportamento das partes e conduta das autoridades responsáveis pela condução do processo. O princípio da razoabilidade também fornece importantes subsídios para esta análise, por meio dos critérios da adequação, necessidade e proporcionalidade, ressaltando-se que deve ser empregado sempre no sentido de conferir maior proteção ao indivíduo em face do pode estatal. / Larticle 5 inscrit dans la LXXVIII Constitution de la République Fédérative du Brésil garantit à tous, dans le domaine judiciaire et administratif, « le droit dêtre jugé dans un délai raisonnable. Il sagit dune garantie dont le contenu est vague et équivoque à plusieurs titres et dont lefficacité dépend dune discipline infraconstitutionnelle qui spécifie son contenu et son étendue. Selon le principe de réserve légale, et en conséquence du principe de séparation des pouvoirs, il appartient au Pouvoir Législatif la délimitation temporelle du pouvoir de punir de lEtat, en limitant la durée de la contrainte émanant du cheminement du procès. Cest seulement en labsence de délais légaux maximum de durée du procès que lon admet lactivité interprétative intégrative de la part du Pouvoir Judiciaire, de façon à garantir lapplicabilité immédiate de la règle concernant les droits fondamentaux. Pour aider à cette difficile tâche herméneutique, détablir une limite à partir de laquelle ne se justifie plus la poursuite du procès, parce que le délai raisonnable de sa durée a été dépassé, certains critères reconnus internationalement peuvent être utilisés, comme cest le cas pour la complexité de la cause, le comportement des parties et la conduite des autorités responsables de la direction du procès. Le principe de la proportionnalité fournit également de nombreux recours pour cette analyse, par lintermédiaire des critères de ladéquation, de la nécessité et de la proportionnalité, soulignant que lon doit toujours lutiliser dans le sens doctroyer une plus grande protection à lindividu face au pouvoir de létat.