MEASUREMENT OF AORTIC INPUT IMPEDANCE

描述（由申请人提供）：候选人Anilkumar Reddy博士，生物工程博士。作为一名博士后，他帮助开发了一种用于小鼠的多普勒信号处理系统。他接受过测量、分析和解释小鼠心血管（CV）系统监测数据的培训，并了解小鼠手术技术。他的直接目标是了解针对小鼠心血管系统的分子和基因操作如何影响动脉系统的机制。作为实现这一目标的第一步，他将专注于使用阻抗技术评估小鼠大动脉硬度。他的长期目标是与他的同事和其他学科的研究人员合作，开发无创的方法来进行有意义和有用的血液动力学测量，可用于小鼠的诊断和治疗，并最终目标是将这些方法扩展到人类。导师博士将提供多学科的培训环境。Hartley, Michael， Taffet和Entman，他们共同拥有电气和生物医学工程，心血管生理学和外科，老年医学和数学，心脏病学和分子生物学方面的专业知识。候选人将拥有DeBakey心脏中心、小鼠心血管生理学实验室、心血管科学部仪器开发实验室、实验室和办公空间、用品、技术帮助、动物模型和其他合作者的全部资源。所有的导师都部分由NIH拨款资助，涉及小鼠心血管生理学的测量和评估，并与候选人的研究主题密切相关。在小鼠和男性中，随着衰老和疾病的发生，动脉系统的机械特性发生变化，并影响心室在主动脉入口处经历的输入阻抗（后负荷）。我们建议根据在主动脉入口测量的压力和流速信号确定的输入阻抗来表征小鼠动脉系统，并使用它来推断小鼠衰老，疾病和遗传模型中的特定血管改变和适应。该项目的具体目的是：(1)比较在基线、血管舒张、血管收缩和不同心率下获得的正常小鼠的主动脉输入阻抗与在相同条件下获得的人类主动脉输入阻抗；(2)对比小鼠脉搏波速度与特征阻抗；(3)将流速和测压得到的主动脉输入阻抗与流速和主动脉内压得到的主动脉输入阻抗进行比较；(4)老龄小鼠和遗传小鼠模型与正常小鼠的主动脉输入阻抗进行比较。由于小鼠的心血管系统在许多方面与人类相似，将阻抗测量方法应用于疾病和遗传小鼠模型有可能对人类血管疾病的理解和诊断和治疗方法的发展做出巨大贡献。

DESCRIPTION (provided by applicant): The candidate, Dr. Anilkumar Reddy has a Ph.D. in Bioengineering. As a postdoctoral fellow he helped to develop a Doppler signal processing system for mice. He has training in the measurement, analysis, and interpretation of data obtained from monitoring the mouse cardiovascular (CV) system, and knows mouse surgical techniques. His immediate goals are to understand how molecular and genetic manipulations targeted at mouse CV system affect the mechanics of the arterial system. As a first step towards this goal he will focus on the assessment of large artery stiffness in the mouse using impedance techniques. His long term goals are to work in consort with his colleagues and investigators from other disciplines, to develop noninvasive methods for making meaningful and useful hemodynamic measurements which can be used in the diagnosis and treatment in mice, and with the end goal of extending these methods to humans. A multidisciplinary training environment will be provided by the mentors Drs. Hartley, Michael, Taffet, and Entman, who together have expertise in electrical and biomedical engineering, cardiovascular physiology and surgery, geriatric medicine and mathematics, and cardiology and molecular biology. The candidate will have full access to the resources of the DeBakey Heart Center, the Murine Cardiovascular Physiology Laboratory, the Instrumentation Development Laboratory within the Section of Cardiovascular Sciences, laboratory and office space, supplies, technical help, animal models, and other collaborators. All of the mentors are funded partially by NIH grants which involve measurement and evaluation of cardiovascular physiology in mice and are closely related to the subject of the candidate's research. Changes in the mechanical properties of the arterial system occur with aging and disease in mice and men, and impact the input impedance (afterload) experienced by the ventricle at the aortic inlet. We propose to characterize the mouse arterial system in terms of input impedance determined from pressure and flow velocity signals measured at the aortic inlet, and use it to infer specific vascular alterations and adaptations in aging, disease and genetic models of mice. The specific aims of this project are: (1) Compare the aortic input impedance of normal mice obtained at baseline, with vasodilation, vasoconstriction, and at varying heart rates to the aortic input impedance reported in humans obtained under the same conditions; (2) Compare pulse-wave velocity to characteristic impedance in mice; (3) Compare aortic input impedance obtained by velocity and tonometric aortic pressure to aortic input impedance obtained by velocity and intra-aortic pressure; (4) Compare the aortic input impedance of aging and genetic mouse models to aortic input impedance of normal mice. Since the cardiovascular system of a mouse is similar to that of humans in many respects applying impedance measurement method to the disease and genetic mouse models has the potential to contribute greatly to the understanding of human vascular diseases and to the development of methods for diagnosis and treatment.