Gender & orthostatic intolerance: mechanisms and therapy

描述(由申请人提供)： 这个以患者为导向的导师研究职业发展奖的全球目标是建立我作为一名学术内科科学家的职业生涯，并过渡到成为一名独立的研究人员。为了实现这一目标，我和我的导师一起制定了一个紧密结合的计划，包括尖端科学和以患者为中心的研究技术方面的高级培训。通过参加德克萨斯大学西南分校以患者为中心的K30课程，我将获得公共卫生硕士学位，我将在研究设计、人类受试者保护、授权书和高级生物统计学方面获得深入的指导。我的导师和顾问委员会由德克萨斯大学西南分校和布里格姆妇女医院的资深科学家组成，我还将获得有关血压控制的肾脏/神经激素机制、生殖内分泌学和临床直立不耐受的关键新研究技能。我的研究计划集中在立位耐力方面的性别差异的潜在机制，包括神经体液对心血管控制过程和决定中心血容量立位分布的生理特征(主要是心脏大小和功能)的影响。将检查年轻女性的月经周期变异性，以及男性、女性和患有慢性直立性不耐受(体位性直立性心动过速综合征，简称POTS)的女性之间的差异。最后，将研究一种特定的干预措施(运动训练)作为POTS患者的治疗方法，并与标准药物疗法(13-受体阻滞剂和容量扩张剂)进行比较。本课程将研究血流动力学和交感神经对Valsalva动作、静态握力、冷升压试验和长时间直立倾斜反应的自主神经控制；将检查长期站立时的静脉小动脉反应和神经体液反应。在拟议的项目完成后，我们将知道特定性别的因素，如月经周期或影响心脏大小和功能的身体因素是否属于年轻女性立位耐受性的决定因素，以及体育运动训练是否可被视为提高患者立位耐力的有效非药物治疗。以病人为中心的研究方面的高级培训和对一个重要临床问题的深入研究相结合，将为我作为一名独立研究员的职业生涯做好准备。

DESCRIPTION (provided by applicant): The global objective of this Mentored Patient-Oriented Research Career Development Award is to build my career as an academic physician-scientist and make the transition to become an independent investigator. To accomplish this goal, together with my mentor, i have developed a tightly integrated plan including cutting edge science, and advanced training in the techniques of patient-oriented research. By participating in the K30 Curriculum in Patient-Oriented Research at UT Southwestern leading towards a MPH degree, I will receive in-depth instruction in research design, protection of human subjects, grantsmanship, and advanced level biostatistics. From my mentor and advisory committee, made up of senior scientists both at UT Southwestern and at the Brigham and Women's Hospital, I also will acquire critical new research skills regarding renal/neurohormonal mechanisms of blood pressure control, reproductive endocrinology, and clinical orthostatic intolerance. My research plan focuses on the mechanisms underlying gender differences in orthostatic tolerance, including neurohumoral influences on cardiovascular control processes and physical characteristics (primarily cardiac size and function) that determine orthostatic distribution of central blood volume. Menstrual cycle variability in young women, and differences among men, women, and women with chronic orthostatic intolerance (Postural Orthostatic Tachycardia Syndrome, or "POTS") will be examined. Finally, a specific intervention (exercise training) will be studied as treatment for patients with POTS and compared with standard pharmacologic therapies (13-blockers and volume expanders). Autonomic neural control of hemodynamic and sympathetic responses to the Valsalva maneuver, static handgrip, a cold pressor test, and prolonged head-up tilt will be investigated; the venoarteriolar response and neurohumoral responses to a long-term standing will be examined. After completion of the proposed project, we will know whether gender-specific factors such as the menstrual cycle or physical factors influencing cardiac size and function are among the determinants for orthostatic intolerance in young women, and whether physical exercise training can be considered an effective non-pharmacologic treatment for patients to improve their orthostatic tolerance. The combination of advanced training in patient-oriented research and in-depth study of an important clinical problem will prepare me well for a career as an independent investigator.