Gender & orthostatic intolerance: mechanisms and therapy

描述（由申请人提供）： 这个指导以患者为导向的研究职业发展奖的全球目标是建立我的职业生涯作为一个学术医生科学家，并过渡到成为一个独立的研究者。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导向的研究技术的高级培训。通过参加K30课程，在UT西南部以患者为导向的研究导致MPH学位，我将接受研究设计，人类受试者的保护，granectin和高级生物统计学的深入指导。从我的导师和咨询委员会，由UT西南和布里格姆妇女医院的高级科学家组成，我还将获得关于血压控制，生殖内分泌学和临床直立不耐受的肾脏/神经激素机制的关键新研究技能。我的研究计划侧重于立位耐力的性别差异的机制，包括心血管控制过程和身体特征（主要是心脏大小和功能）的神经体液的影响，决定直立中心血容量的分布。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不耐受（体位性心动过速综合征，或“POTS”）的女性之间的差异。最后，将研究特定干预（运动训练）作为POTS患者的治疗，并与标准药物治疗（13受体阻滞剂和容量扩张剂）进行比较。将研究对Valsalva动作、静态握力、冷加压试验和长时间头高位倾斜的血流动力学和交感神经反应的自主神经控制;将检查对长期站立的静脉动脉反应和神经体液反应。在建议的项目完成后，我们将知道性别特异性因素，如月经周期或影响心脏大小和功能的物理因素是否是年轻女性立位不耐受的决定因素，以及体育锻炼训练是否可以被认为是一种有效的非药物治疗，以改善患者的立位耐受性。在以患者为导向的研究和一个重要的临床问题的深入研究的高级培训相结合，将我准备好作为一个独立的研究者的职业生涯。

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.