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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Mentored Quantitative Research Career Development Award (K25)
Project #
5K25HL073041-04
Application #
7384454
Study Section
Special Emphasis Panel (ZHL1-CSR-Q (F3))
Program Officer
Commarato, Michael
Project Start
2005-04-01
Project End
2010-03-31
Budget Start
2008-04-01
Budget End
2009-03-31
Support Year
4
Fiscal Year
2008
Total Cost
$142,918
Indirect Cost
Name
Baylor College of Medicine
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
051113330
City
Houston
State
TX
Country
United States
Zip Code
77030
Reddy, Anilkumar K; Hartley, Craig J; Pham, Thuy T et al. (2014) Young little mice express a premature cardiovascular aging phenotype. J Gerontol A Biol Sci Med Sci 69:152-9
Gurha, Priyatansh; Wang, Tiannan; Larimore, Ashley H et al. (2013) microRNA-22 promotes heart failure through coordinate suppression of PPAR/ERR-nuclear hormone receptor transcription. PLoS One 8:e75882
Crossland, Randy F; Durgan, David J; Lloyd, Eric E et al. (2013) A new rodent model for obstructive sleep apnea: effects on ATP-mediated dilations in cerebral arteries. Am J Physiol Regul Integr Comp Physiol 305:R334-42
Gurha, Priyatansh; Abreu-Goodger, Cei; Wang, Tiannan et al. (2012) Targeted deletion of microRNA-22 promotes stress-induced cardiac dilation and contractile dysfunction. Circulation 125:2751-61
Nagamani, Sandesh C S; Campeau, Philippe M; Shchelochkov, Oleg A et al. (2012) Nitric-oxide supplementation for treatment of long-term complications in argininosuccinic aciduria. Am J Hum Genet 90:836-46
Hartley, Craig J; Reddy, Anilkumar K; Madala, Sridhar et al. (2010) Feasibility of dual Doppler velocity measurements to estimate volume pulsations of an arterial segment. Ultrasound Med Biol 36:1169-75
Namiranian, Khodadad; Lloyd, Eric E; Crossland, Randy F et al. (2010) Cerebrovascular responses in mice deficient in the potassium channel, TREK-1. Am J Physiol Regul Integr Comp Physiol 299:R461-9
Hartley, Craig J; Reddy, Anilkumar K; Michael, Lloyd H et al. (2009) Coronary flow reserve as an index of cardiac function in mice with cardiovascular abnormalities. Conf Proc IEEE Eng Med Biol Soc 2009:1094-7
Reddy, Anilkumar K; Namiranian, Khodidad; Lloyd, Eric E et al. (2009) Effect of isoflurane on aortic impedance in mice. Conf Proc IEEE Eng Med Biol Soc 2009:1104-5
Reddy, Anilkumar K; Madala, Sridhar; Jones, Alan D et al. (2009) Multichannel pulsed Doppler signal processing for vascular measurements in mice. Ultrasound Med Biol 35:2042-54

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