京都大学 / 新制・課程博士 / 博士(医学) / 甲第23607号 / 医博第4794号 / 新制||医||1055(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 溝脇 尚志, 教授 木村 剛, 教授 濵﨑 洋子 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Objective: Midlife obesity is a risk factor for dementia development. Obesity has also been linked to hyperaldosteronism, and this can be modeled in rats by high fat (HF) feeding from weaning. Aldosterone, or activation of the mineralocorticoid receptor (MR) causes cerebrovascular injury in lean hypertensive rats. We hypothesized that rats fed a HF diet would show inward middle cerebral artery (MCA) remodeling that could be prevented by MR antagonism. We further proposed that the cerebral artery remodeling would be associated with white mater injury. Methods: Three-week-old male Sprague-Dawley rats were fed a HF diet ± the MR antagonist canrenoic acid (Canr) for 17 weeks. Control rats received normal chow (control NC). MCA structure was assessed by pressure myography. Results: The MCAs from HF fed rats had smaller lumens and thicker walls when compared to arteries from control NC rats; Canr prevented the MCA remodeling associated with HF feeding. HF feeding increased the mRNA expression of markers of cell proliferation and vascular inflammation in cerebral arteries and Canr treatment prevented this. White mater injury was increased in the rats fed the HF diet and this was reduced by Canr treatment. The expression of doublecortin, a marker of new and immature neurons was reduced in HF fed rats, and MR antagonism normalized this. Conclusions: These data suggest that HF feeding leads to MR dependent remodeling of the MCA and this is associated with markers of dementia development.

It is widely accepted that sleep disturbances occur in patients recovering from coronary artery bypass graft (CABG) surgery. This sleep disturbance, at least in theory, might retard or limit the return of functionality and exacerbate psychological states known to increase use of health care services and adversely affect prognosis. This study explored possible relations between sleep, self-rated aerobic physical capacity and physical activity in a sample of patients who underwent CABG surgery. Secondary analysis investigated the possible concurrent influences of post-CABG health complaints and depression on sleep function. Measures included the Pittsburgh Sleep Quality Questionnaire; the Veterans Specific Activity Questionnaire; the Paffenbarger Physical Activity Questionnaire; the Health Complaint Scale and the Beck Depression Inventory, Version II. The physical measure of body composition was also used. Fifty-five subjects completed baseline questionnaires for all measures just prior to surgery, excluding the Paffenbarger Physical Activity Questionnaire. Follow-up evaluations were repeated at 3 mo post-CABG for the same measures and the patients were also asked to report their patterns of post-surgical physical activity involvement. Correlation coefficients were calculated to determine whether a correlation existed between the measures. Significant correlations were found between pre-surgical and post-surgical sleep score, sleep subscales, functional capacity, depression and health complaints (p < 0.05). Post-CABG sleep and physical activity did not exhibit a significant correlation. A number of secondary analyses were performed in an effort to isolate possible influences of confounding factors, such as depression, body mass index > 27, and a ventricular ejection fraction (EF) < 30. In the low EF subgroup, overall sleep score and self-rated functional capacity were strongly correlated before surgery was performed (r = -0.85; p < 0.01). Stepwise regression equations were constructed to predict sleep outcome before and after surgery. Somatic health complaints, depression, and skinfold measures were found to be predictors for pre-surgical sleep (R2 = 0.52), as well as post-surgical sleep (R2 = 0.78). Fitness measures of functional capacity and physical activity were not a significant predictor of sleep. The findings of this study suggest that a modest correlation exists between functional capacity and sleep in CABG patients; however, predictors including health complaints, depression and skinfold measures serve as better indicators for sleep outcome before and after CABG surgery. / Master of Science

BACKGROUND: Previous research has shown that the ventilatory threshold (VT) correlates highly with onset of lactate accumulation and maximal steady-state exercise (MSS) level. Also, studies have shown the VT is useful in prescribing exercise for cardiac patients in that it gives an exercise intensity at which the patient is metabolically stable. METHODS: The purpose of this study was to determine if a MSS response could be achieved at an exercise intensity corresponding to the VT for patients with CAD. A group of 31 patients with CAD performed a maximal effort treadmill exercise test in which respiratory gas exchange was measured. The VT was determined using the V-slope method of computer regression analysis of the plot of carbon dioxide production versus oxygen consumption. Subjects then performed a constant load treadmill test a speed and grade that corresponded to the VT. Heart rate (HR), systolic blood pressure (SBP), and rating of perceived exertion (RPE) evaluated for steady-state responses. If subjects showed a steady-state response in two of these three parameters they were scored as having achieved a maximal steady-state (MSS+) response; those not meeting this standard were scored as failing to achieve maximal steady-state (MSS-) response. Subjects were analyzed as an entire group (N=31), as well as analyzed in subsets according to history of myocardial infarction (MI+, N=20; MI-, N=11) and administration of beta-blocker medications (BB+, N=16; BB-, N=15). RESULTS: Overall, subjects demonstrated significantly more MSS+ responses than MSS- responses (80% Vs 20%, P<0.05). Analysis of the subgroup data showed that it was the patient s with a history of MI (MI+ =85%, P<0.05) and those not receiving beta-blocker medications (BB- = 93%, P<0.05) who had significantly greater proportions of subject achieving MSS+ responses in the fixed load exercise condition. Conversely patient in the MI- (73 %, P < 0.05) and BB (69% P < 0.05) groups showed no significant differences in the number of MSS+ and MSS- responses. CONCLUSIONS: The VT, as measured during ramp exercise testing on the treadmill, provided a basis for establishing a maximal steady-state load in terms of cardiovascular and perceptual variables for 80% of the patients in the CAD study group. The measurements of HR, SBP, and RPE are easily obtained in a clinical setting and thus enable the VT to be used in bringing about a more efficacious exercise prescription. The validity of this method may be questioned, however, for patient with out a history of MI and for those receiving beta-blocker medications. / Master of Science

No description available.

Les stents sont aujourd’hui le traitement le plus courant des stades avancés de l’athérosclérose. Le concept de stents bioresorbables (BRS) est basé sur l’idée qu’un stent n’est nécessaire que jusqu’à la guérison de l’artère – suite à quoi il serait préférable que le stent disparaisse, afin de retrouver un état plus physiologique. Le déploiement d’un stent altère significativement les contraintes mécaniques exercées sur la paroi artérielle, or celles-ci jouent un rôle important dans l’incidence de complications telle que la resténose et l’hyperplasie néointimale. Dans le cas d’un BRS, les contraintes mécaniques dans le stent comme dans la paroi artérielle évoluent au fur et à mesure que le stent se dégrade. De plus, la dégradation du stent par hydrolyse peut être accélérée par ces contraintes : un couplage supplémentaire qui doit être pris en compte. Nous nous intéressons à la détermination de l’évolution des contraintes dans le stent et dans l’artère pendant le déploiement puis la dégradation du stent, ainsi qu’à l’influence de ces contraintes sur la dégradation du stent et sur le remodelage de la paroi, qui est également influencé par la dénudation de l’endothélium et par l’inflammation induite par l’implantation d’un BRS. Pour atteindre ces objectifs, nous avons développé un modèle 3D par éléments finis du déploiement et de la dégradation d’un BRS en acide polylactique tenant compte du couplage entre l’artère et le stent. Il permet notamment de prédire les zones de démantèlement dustent et l’évolution de l’épaisseur de la paroi artérielle en réponse à l’implantation d’un BRS. Etant donné que le modèle repose fortement sur des paramètres qui doivent être déterminés expérimentalement, nous nous sommes intéressés au développement d’une méthode expérimentale pour suivre la dégradation d’un BRS. Nous avons utilisé la tomographie par cohérence optique (OCT) pour suivre régulièrement la dégradation de stents déployés dans des tubes et immergés dans du sérum physiologique à 37°C pendant deux ans. Nous avons ensuite développé une méthode qui détecte automatiquement les struts des stents sur les images OCT et quantifie leur intensité de niveau de gris. Les résultats suggèrent que cette méthode automatisée d’analyse d’images OCT est un outil prometteur pour évaluer quantitativement l’état de dégradation d’un BRS. Enfin, nous nous sommes intéressés à la capacité d’une artère stentée à s’adapter à une modification du cisaillement ressenti. Nous avons étudié l’évolution de la lumière artérielle de porc stentés suivis in vivo par OCT ainsi que le cisaillement associé. Alors qu’un stent métallique bloque le remodelage artériel, nous avons observé qu’un BRS – probablement grâce au démantèlement du stade final de la dégradation – libère le vaisseau et permet ainsi l’adaptation de son diamètre de manière à diminuer le cisaillement et l’inadéquation avec l’artère non stentée. L’adaptation de la lumière artérielle permise par le démantèlement du stent pourrait être prise en compte dans de futurs modèles numériques. / Today, sent deployment is the most common treatment for symptomatic atherosclerosis. Bioresorbable stents (BRS) are based on the premise that a stent is needed only until arterial wound healing occurs after which it would be desirable for the stent to degrade so that the arterial wall recovers its natural compliance. Deployment of a stent profoundly alters the mechanical environment in the arterial wall, and these alterations play an important role in regulating the incidence of complications such as restenosis and neointimal hyperplasia. In the case of a BRS, the mechanical stresses in both the stent and the arterial wall evolve as the stent degrades. Furthermore, the hydrolysis-driven degradation of the stent can be accelerated by mechanical stresses in the stent, an additional coupling that needs to be taken into account. We are interested in determining the evolution of stresses in both the stent and the arterial wall during the stent deployment and degradation process and in elucidating the effect of these stresses on the stent degradation and on the remodeling process in the wall, which would also be influenced by the loss of endothelial cells and the amount of inflammation induced by the stent deployment and degradation. To this end, we have developed a 3D finite element model of the deployment and degradation of a polylactic acid (PLA) BRS that integrates the coupling between the stent and the artery.This allows one to predict the zones of dismantling of the stent and the evolution of the arterial thickness in response to a BRS stenting procedure. Since the model relies strongly on parameters that need to be determined experimentally, we became interested in developing methods to follow stent degradation. With this aim, we used optical coherence tomography (OCT) to image several BRS that were deployed into tubes and allowed to degrade in a saline solution at 37°C over a period of two years. We subsequently developed a versatile method for automatically detecting stent struts on the OCT images and quantifying the strut gray scale intensity. The results suggest that this automated method of OCT image analysis represents a promising tool to quantitatively assessing BRS degradation states. Lastly, we were interested in establishing the ability of a stented artery to adapt to a modification in its wall shear stress. Studying the in vivo evolution of the lumen of stented mini-swine arteries followed by OCT imaging allowed us to demonstrate that whereas a bare metal stent cages the artery, a BRS, presumably due to its degradation-induced dismantling, frees the vessel and enables it to adapt its lumen diameter in order to decrease its absolute level of shear stress and the compliance mismatch with the unstented portion of the artery. This lumen adaptation allowed by the stent dismantling could be taken into account in future computational models.

京都大学 / 0048 / 新制・論文博士 / 博士(医学) / 乙第12888号 / 論医博第2088号 / 新制||医||1007(附属図書館) / 31642 / (主査)教授 小泉 昭夫, 教授 平家 俊男, 教授 福山 秀直 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第20283号 / 医博第4242号 / 新制||医||1021(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 湊谷 謙司, 教授 福原 俊一, 教授 横出 正之 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第20621号 / 医博第4270号 / 新制||医||1023(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 山下 潤, 教授 木村 剛, 教授 渡邉 大 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第21666号 / 医博第4472号 / 新制||医||1035(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 松田 文彦, 教授 佐藤 俊哉, 教授 Shohab YOUSSEFIAN / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM