MEASUREMENT OF AORTIC INPUT IMPEDANCE IN MICE

Baylor College Of Medicine, Houston TX

Investigators

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Abstract

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.