MEASUREMENT OF AORTIC INPUT IMPEDANCE

描述(申请人提供)：候选人Anilkumar Reddy博士拥有生物工程博士学位。作为博士后，他帮助开发了一种用于老鼠的多普勒信号处理系统。他接受过测量、分析和解释通过监测小鼠心血管(CV)系统获得的数据的培训，并了解小鼠外科技术。他的近期目标是了解针对小鼠心血管系统的分子和遗传操作如何影响动脉系统的机械结构。作为迈向这一目标的第一步，他将专注于使用阻抗技术评估小鼠的大动脉硬度。他的长期目标是与他的同事和其他学科的研究人员合作，开发非侵入性方法，进行有意义和有用的血流动力学测量，用于小鼠的诊断和治疗，最终目标是将这些方法推广到人类。Hartley博士、Michael博士、Taffet博士和Entman博士的导师将提供一个多学科的培训环境，他们共同拥有电气和生物医学工程、心血管生理学和外科、老年医学和数学以及心脏病学和分子生物学方面的专业知识。应聘者将完全使用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资源。所有的导师都部分由美国国立卫生研究院的拨款资助，这涉及到对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。动脉系统的机械特性会随着年龄的增长和人类的疾病而发生变化，并影响主动脉入口处的心室所经历的输入阻抗(后负荷)。我们建议根据从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的动脉系统，并使用它来推断小鼠衰老、疾病和遗传模型中特定的血管变化和适应。该项目的具体目标是：(1)比较在相同条件下获得的基线、血管扩张、血管收缩和不同心率下的正常小鼠的主动脉输入阻抗与人类在相同条件下获得的主动脉输入阻抗；(2)比较脉搏波速度与小鼠的特征阻抗；(3)比较由速度和眼压获得的主动脉输入阻抗与通过速度和主动脉内压获得的主动脉输入阻抗；(4)比较衰老和遗传小鼠模型的主动脉输入阻抗与正常小鼠的主动脉输入阻抗。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到疾病和遗传小鼠模型中，可能会对理解人类血管疾病和发展诊断和治疗方法做出巨大贡献。

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.